	Clinical trials play a critical role in evaluating the safety and efficacy of drugs, medical devices, and other products before they are made available to patients. However, clinical trials can take many years to complete before the results become available to apply to patient care.   

	Observational studies using real-world evidence (RWE) provide significant opportunities to gain insight into treatment patterns and outcomes in clinical practice outside randomized controlled trials, as patients enrolled in clinical trials may be in better health and less diverse than the general patient population.  

	RWE is becoming increasingly important for the development of treatment strategies in oncology. In its simplest form, RWE is health care information collected outside formal clinical trials, including electronic health records (EHRs), billing databases, and product and disease registries. The integration of evidence from real-world utilization with data from clinical trials holds the promise of providing information on larger populations of patients with cancer to understand disease epidemiology, pharmacoeconomics, and patient experience.  

	The FDA issued guidance in August 2016 with its “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,” in which it describes the circumstances in which RWE may be used to support a variety of FDA regulatory decisions.

 The 21st Century Cures Act, approved by Congress in December 2016, requires the FDA to develop a framework and guidance for evaluating RWE in the context of drug regulation to support the approval of new drugs and the approval of new indications for previously approved drugs and to support post-approval study requirements.

	In what may be a preview of this pending guidance, 15 FDA officials, including FDA Commissioner Robert Califf, published an editorial about the potential uses of RWE in the New England Journal of Medicine titled “Real-World Evidence—What Is It and What Can It Tell Us?”

Opportunities and Benefits of Real-World Evidence

	To understand the treatment of oncology patients, it is critical to evaluate clinical data points (biomarkers, disease staging, location of metastases, disease progression, etc) as well as elements of the patient experience (adherence rates, reason for treatment discontinuation, toxicities, functional status, etc). RWE also provides the opportunity to better understand rare disease types in smaller populations, in which clinical trials may be difficult to perform and evidence is sparse.  

	The US Oncology Network is a group of more than 60 independent community oncology practices comprising over 1400 physicians treating more than 900,000 patients per year. Many practices use McKesson Specialty Health’s iKnowMed EHR, which captures outpatient medical histories from community oncology practices across 19 states. Through use of a shared EHR platform, physicians are able to perform research in collaboration with pharmaceutical companies to answer important scientific questions that are relevant for drug development and help improve the outcomes of patients. Here are 3 main ways that the medical community can use RWE to help improve health outcomes.  

Efficient Drug Development for Unmet Needs 

	RWE complements research studies and clinical trials, delivering insight into the use of drugs and treatment patterns in daily practice. This ultimately provides a more comprehensive view of patient outcomes to medications and a better understanding of disease patterns that may not be identified in smaller samples. These patterns can reveal additional indications for medications already in widespread use. 

	This is a particular area of opportunity in oncology, in which treatment decisions are affected by the fact that there are many forms of disease, diseases with short survival times, and many rare conditions that have a lack of evidence, no approved treatment, or only conditional approvals. With the ability to analyze large data sets, investigators can use RWE to conduct postapproval studies to discover patterns that may not be visible in smaller sample sizes. This is critical to help support new indications for medicines and improve patient care. 

	One such condition is metastatic Merkel cell carcinoma (mMCC). An uncommon, aggressive skin cancer, mMCC has one of the highest mortality rates across all skin cancer types, with an overall survival rate of only 40%. Fewer than half of patients who receive the diagnosis survive more than a year. Despite incidence of mMCC dramatically increasing over the past 20 years, development of an evidence-based standard therapeutic regimen was lagging. As a result, treatment for mMCC centered on a therapy primarily used for patients with small cell lung cancer. 

	In a study performed through The US Oncology Network using McKesson Specialty Health’s iKnowMed oncology EHR, a substantial patient population who received a diagnosis of mMCC and were treated for it was identified. By using iKnowMed to identify an mMCC patient population, investigators were able to conduct a study of historical treatment therapy responses, to help interpret the outcomes of single-arm clinical trials, and help establish an FDA-approved first-line therapy for mMCC. Through iKnowMed, 686 patients with mMCC were identified, and one-third of these patients had metastatic disease. After applying eligibility criteria similar to that of the clinical trial being conducted in mMCC, 67 patients were deemed eligible for the RWE study.

	Real-world retrospective analyses of patients with distant mMCC who received first-line or second-line and later chemotherapy indicated that although responses were observed with chemotherapy, the duration of such responses was brief and associated with poor overall outcomes in patients with mMCC. These results underscored the need for novel therapeutic approaches. With initial evidence suggesting that immune checkpoint inhibitors had the potential to dramatically improve treatment outcomes, results were submitted. Within a year of the study’s conclusion, the FDA granted approval of a new first-line therapy for mMCC.

	“The pharmaceutical industry is increasingly realizing that observational studies using real-world data have promise to efficiently support various phases of the therapeutic innovation process,” said Jennifer Frytak, executive director of health economics and outcomes research development at McKesson Specialty Health. “This approval of a first-line therapy for Merkel cell carcinoma is a tremendous example of how real-world data provided essential information that was needed to support this successful FDA submission, which permitted this drug to become available to patients in need of treatment.”

	Payers and other health care professionals often have to make decisions about access, coverage, reimbursement, and formulary placement for treatments for which data are limited. Offering insight into how a drug performs in real-world clinical settings, RWE can help provide a more comprehensive view of patient response to medications, a better understanding of disease patterns, and improved patient safety information and economic analyses.  

	Clinical trials play a critical role in evaluating the safety and efficacy of drugs; however, there is rarely comparative effectiveness data available at the time of approval. That is, what is the gap between efficacy and effectiveness? With the ability to track more patients over a longer period of time, RWE plays an important role in capturing evidence to demonstrate how a drug may affect patients and health care costs in real-world settings by helping to answer the following questions:

		How does one drug perform versus another in terms of treating a particular condition or subset of patients?  

		How does one drug perform against previously approved medications?

		How does the drug perform when patients have multiple conditions with multiple medications?  

		Which environmental factors affect the effectiveness of the treatment?

		Are there drug interactions that affect performance or safety?

		What are the observed benefits of the medication as it is prescribed and used by doctors and patients in real clinical settings?

	The Centers for Medicare & Medicaid Innovation’s Oncology Care Model pilot, which began in July 2016, is an alternative payment model designed to test whether specific changes in cancer care delivery can result in “better care, smarter spending and healthier people.”

 As new reimbursement models evolve with a focus on outcomes and affordability, the use of EHR data enables the retrospective assessment of known findings in the context of real clinical practice settings, adding new insights at a large scale. For example, payers and manufacturers are currently evaluating novel pricing and reimbursement models based on real-world evidence. RWE may also help improve formulary placement decisions based on longer-term medical cost and outcomes data.  

	“Real-world evidence represents a meaningful step toward personalized health care, as it helps pinpoint patient characteristics that can be used to improve medicine’s ability to meet the needs of individual patients. With more comprehensive data about the real clinical performance of a medication, we can make more informed decisions about access and formulary inclusion, which will help improve patient outcomes, especially when it comes to chronic or rare disease states,” said Nicholas Robert, MD, medical oncologist with The US Oncology Network and medical director for heath informatics and health economics and outcomes research at McKesson Specialty Health.

	Collecting posttrial information about a drug in real time, RWE provides insights into utilization and treatment patterns, patient adherence, and disease management opportunities that can improve patient care and support quality-improvement programs.

	Following FDA approval of a new drug, the postapproval monitoring process occurs. The growing use of expedited reviews for FDA approvals increases the need for longer-term postmarketing safety studies to identify adverse events, thereby limiting potential harm. Traditional adverse event reporting from clinicians, patients, and manufacturers remains the primary source of safety information. RWE provides considerable opportunity to improve post-market surveillance activities through other methods of data collection. RWE also provides the opportunity to examine longer-term outcomes among populations in which conditional approvals may exist.   

	The use of oral oncolytics is rapidly expanding, giving patients promising new treatment options. In 2015, 9 oral cancer drugs were approved by the FDA,7 and of the 836 cancer medications and vaccines in clinical development, approximately one-quarter are oral agents.

	While oral oncolytics offer significant convenience for patients, the transition of treatment from the physician office reduces the ability of clinicians to track how patients are taking the medications. Research shows that nonadherence rates with oral oncolytics are more than 20%.

 Analyses of RWE— including pharmacy and administrative claims data&mdash;may help identify potential problem areas and enable pharmacists, manufacturers, and providers to support adherence and positive outcomes by offering education, resources, and behavioral coaching.  

	RWE can also help identify whether eligible patient populations are getting access to the treatment with specific targeted therapies. Postlaunch studies can improve understanding of prescriber preferences for treatment options available in treatment guidelines or FDA-approved labels, as well as provide real-world insights into trends regarding physician adoption, sequencing, or education issues that may affect adoption.

Conclusion: The Importance of Real-World Evidence

	To understand the treatment of oncology patients, it is critical to evaluate clinical data points and elements of the patient experience. In addition to more efficient drug development and commercialization for the pharmaceutical industry, the generation of RWE from comprehensive EHR databases provides value in improving patient care through better understanding of real-world treatment patterns, utilization, and patient safety. Ultimately, the ability to quickly gather evidence can help improve health outcomes for patients through better understanding of the effectiveness of medications in the real world.

		US Food and Drug Administration. Use of real-world evidence to support regulatory decision-making for medical devices: guidance for industry and Food and Drug Administration staff. 

www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm513027.pdf

		Hills B, Zegarelli B. 21st Century Cures Act requires FDA to expand the role of real world evidence. 

healthlawpolicymatters.com/2016/12/19/21st-century-cures-act-requires-fda-to-expand-the-role-of-rwe/

		Sherman, RE, Anderson SA, Dal Pan GJ, et al. Real-world evidence —what is it and what can it tell us? 

. 2016;375(23):2293-2297. doi: 10.1056/NEJMsb1609216.

		Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicenter, single-group, open-label, phase 2 trial. 

2016;17(10):1374-1385. doi: 10.1016/S1470-2045(16)30364-3.

		Avelumab (Bavencio). US Food and Drug Administration website. 

www.fda.gov/drugs/informationondrugs/approveddrugs/ucm547965.htm

		Oncology Care Model. US Centers for Medicare & Medicaid Services website.

innovation.cms.gov/initiatives/oncology-care/

		Egerton, N. In-office dispensing of oral oncolytics: a continuity of care and cost mitigation model for cancer patients. 

		Brown, MT, Bussell, JK. Medication adherence: WHO cares? 

Articles

Features

Real-world evidence is becoming increasingly important for the development of treatment strategies in oncology.

Value of Real-World Evidence in Improving Patient Outcomes in Oncology

	Specialty pharmacies service patients who require high-cost or “high-touch” medications for treating rare, chronic, or complex disease states such as cancer, multiple sclerosis, hepatitis C, rheumatoid arthritis, and rare genetic disorders. Products dispensed by specialty pharmacies include oral, injectable, and intravenous (IV) medications, ranging from those approved by the FDA up to 7 decades ago to newly approved therapies from the drug development pipeline. In disease states that carry a poor prognosis or lack suitable treatment options, such as certain types or stages of cancer, a newly approved product may bring newfound hope to a patient who previously faced mortality. No other field has generated as much excitement as cancer care in this regard.

	In 2012, congressional lawmakers approved the Food and Drug Administration Safety and Innovation Act (FDASIA), which allows the FDA to use surrogate clinical end points to grant accelerated or expedited approval of products that treat serious medical conditions and fill an unmet need. Regarding oncology clinical trials, these end points must be significantly superior to currently available treatments and usually include overall response rate data rather than overall survival data. Due to a streamlined approval process, the FDA has greenlit 56 novel oncology products since January 1, 2013, 52% of which are orally available anticancer agents.  

	Oncology limited distribution drug (LDD) networks range in size from a single specialty pharmacy provider to more than 20. In certain circumstances, a sole entity is responsible for 100% of a product’s prescription dispensing. If a manufacturer decides to provide access to their product via an LDD network, the member specialty pharmacies become de facto experts on the drug. In a newly FDA-approved LDD product launch, specialty pharmacies have a responsibility to provide their employees, prescribing customers—physicians, nurse practitioners, and physician assistants&mdash;and patients with complete drug information. Additionally, member specialty pharmacies are obligated to provide certain data metrics to product manufacturers to help them ascertain the real-world applications of their newly approved product, as well as assess how postmarketing clinical data compare with clinical trial data.

	Specialty pharmacies provide thorough clinical education regarding all newly approved medications to employees who are involved in patient care—pharmacists, pharmacy technicians, patient advocates (such as those who source funding), billing team members, procurement/inventory team members, and information technology staff. New product education is typically provided in coordination with an expert from the manufacturer, such as a medical science liaison. Fully educating all appropriate employees improves a specialty pharmacy’s operational efficiency, from having the right protocols built into the patient care system to ensuring that pharmacists possess the right knowledge and access to information so they can perform critical counseling to patients on the new drug.

	To provide optimal care to patients with complex, rare, or life-threatening illnesses, specialty pharmacies must develop and maintain relationships with their prescribing customers. It is incumbent on the specialty pharmacy to not only promote awareness regarding newly approved products but also to serve as an information resource regarding a medication. Often, prescribers have no experience in treating patients receiving a new drug unless they participated in its clinical trials. Specialty pharmacies play a critical role in informing prescribers of appropriate dosing regimens, clinically relevant drug interactions, laboratory monitoring parameters, and required supportive care related to the new product. During the launch phase and through early adoption and early majority, these services are particularly critical.

	As the nature of cancer treatment changes from patients receiving IV infusions in an outpatient or inpatient setting to patients administering oral oncolytics at home, the responsibilities of specialty pharmacy practices in direct patient care are growing exponentially. Traditionally, specialty pharmacies have been viewed as facilities that dispense medications and mail them to patients. Due to the complexity of care involved with patients battling cancer, specialty pharmacies, such as Onco360, have taken a new approach to assisting patients throughout their therapeutic journey. In addition to offering core services, such as prescription fulfillment and new medication counseling, specialty pharmacies seek to provide all patients with the means to afford their medications. Whether through third-party foundation assistance or manufacturer-based free-drug programs, specialty pharmacies attempt to alleviate the financial toxicities of cancer care as much as possible. 

	As cancer treatment transitions from the clinic to the home setting, diminishing prescribers’ oversight of their patients’ care, the role of the pharmacist as a midlevel practitioner has expanded. Onco360 aims to serve as an extension of the prescriber’s office by performing medication therapy management (MTM) for patients receiving particularly high-touch oral oncolytic agents. MTM programs focus mainly on outbound support calls to patients at scheduled intervals to help maintain compliance with cancer treatment regimens and prevent or manage adverse effects (AEs). 

	Specialty pharmacies engage in pharmacovigilance programs geared toward identifying adverse drug reactions and AEs related to newly approved products. Oncology products may be approved based on phase 1 or 2 clinical trial data, which usually contain smaller patient populations than phase 3 clinical trials. Specialty pharmacies, through their care of patients, fill the void by collecting and providing integral safety data that would otherwise be unavailable to manufacturers. Product manufacturers use that data for required postmarketing surveillance and pharmacovigilance programs that are instrumental in delineating new safety signals. Additionally, specialty pharmacies track other patient care utilization metrics and outcomes related to newly approved mediations, such as duration of therapy, rate of prescription discontinuation, and reasons for discontinuation. These data provide manufacturers with visibility into the real-world patient experience with their product. 

	In conclusion, specialty pharmacies serve as a vital component to the success of a medication newly approved by the FDA. Through interactions with prescribers, patients, and manufacturers, specialty pharmacies function as a valuable intermediary for distribution of drug information, provision of exceptional care for clinically complex patients, and engagement in postmarketing surveillance.

Specialty pharmacies function as a valuable intermediary between stakeholders for the distribution of drug information, provision of exceptional care for complex patients, and engagement in postmarketing surveillance.

New Therapies and the Role of Specialty Pharmacy Providers

	As we head into 2018, we’ve assembled the second part of our annual review of specialty pharmacy—related FDA approvals and expanded indications that took place over the past year. The first installment reviewed non-oncology specialty actions in 2017, while this installment reviews approvals related to oncology drugs and late-breaking FDA actions that took place after the first installment was published in November last year. Please consult the respective product prescribing monographs for complete information, including dosing regimens.

	New oncology molecular entities that were approved in 2017 are detailed below and previously approved oncology drugs that received expanded indications in 2017 are listed in the 

	On April 25, 2017, Xatmep (methotrexate) was approved by the FDA for the treatment of pediatric patients with acute lymphoblastic leukemia as a component of a combination chemotherapy maintenance regimen and for the management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who are intolerant of or had an inadequate response to first-line therapy. Xatmep is a folate analog metabolic inhibitor available in a ready-to-use oral solution of methotrexate that eliminates the need for needles and the crushing of tablets and compounding into a liquid formulation. Prior to dispensing, Xatmep should be refrigerated (2°C-8°C/36°F-46°F), and after dispensing, it may be stored at room temperature (20°C-25°C/68°F-77°F) for up to 60 days, with excursions permitted to 15°C to 30°C (59°F-86°F). The recommended starting dose in multi-agent combination chemotherapy maintenance regimens is 20 mg/m2 once weekly and, for pJIA, 10 mg/m2 once weekly. Patients should be advised that the recommended dose is once per week and that mistaken daily dosing of Xatmep has led to fatal toxicity.

	On April 28, 2017, Rydapt (midostaurin) was approved by the FDA for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults with an fms-like tyrosine kinase 3 (FLT3 gene) mutation and for the treatment of advanced systemic mastocytosis, which includes aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Rydapt is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML. Rydapt is a kinase inhibitor and is available in a 25-mg capsule. The recommended dose for Rydapt in patients with AML is 50 mg orally twice daily with food and, for those with ASM, SM-AHN, or MCL, 100 mg orally twice daily with food.

 (rituximab and hyaluronidase human) was approved by the FDA for the treatment of adult patients with previously untreated and relapsed or refractory follicular lymphoma (FL), previously untreated diffuse large B-cell lymphoma (DLBCL), and previously untreated and previously treated chronic lymphocytic leukemia (CLL). 

 is a combination of rituximab (a CD20-directed cytolytic antibody) and hyaluronidase human (an endoglycosidase). This new treatment includes the same monoclonal antibody as intravenous (IV) Rituxan (rituximab) in combination with hyaluronidase human, an enzyme that helps to deliver rituximab under the skin. Treatment should begin only after patients have received at least 1 full dose of a rituximab product by IV infusion, and 

 is not indicated for the treatment of nonmalignant conditions. The recommended dose for FL/DLBCL is 1400 mg/23,400 units (1400 mg rituximab and 23,400 units hyaluronidase) and for CLL is 1600 mg/26,800 units (1600 mg rituximab and 26,800 units hyaluronidase) subcutaneously according to the dosing schedule outlined in the prescribing information. 

 is available as a solution of 1400 mg of rituximab and 23,400 units of hyaluronidase human per 11.7 mL (120 mg/2000 units per mL) and a solution of 1600 mg of rituximab and 26,800 units of hyaluronidase human per 13.4 mL (120 mg/2000 units per mL) in a single-dose vial.

	On August 1, 2017, Idhifa (enasidenib) was approved by the FDA for the treatment of patients with relapsed or refractory AML with an isocitrate dehydrogenase 2 (IDH2 gene) mutation as detected by an FDA-approved test. Idhifa is approved for use with a companion diagnostic, the Real Time IDH2 Assay, which is used to detect specific mutations in the IDH2 gene in patients with AML. Idhifa was granted Priority Review and Orphan Drug designations. It is an IDH2 inhibitor that is available in 50-mg and 100-mg tablets. The recommended dose of Idhifa is 100 mg orally once daily until disease progression or unacceptable toxicity.

	On August 3, 2017, Vyxeos (cytarabine and daunorubicin) received FDA approval for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Vyxeos was granted Priority Review, Breakthrough Therapy, and Orphan Drug designations by the FDA. It is available as a fixed-combination medication consisting of 2 chemotherapy drugs: 44 mg daunorubicin (an anthracycline topoisomerase inhibitor) and 100 mg cytarabine (a nucleoside metabolic inhibitor encapsulated in liposomes as a lyophilized cake in a single-dose vial for reconstitution). The recommended induction dose of Vyxeos (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome via IV infusion is more than 90 minutes on days 1, 3, and 5 and on days 1 and 3 for subsequent cycles of induction if needed. The consolidation dose of Vyxeos (daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) liposome via IV infusion is more than 90 minutes on days 1 and 3.

	On August 17, 2017, Besponsa (inotuzumab ozogamicin) was approved by the FDA for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Besponsa was granted Priority Review, Breakthrough Therapy, and Orphan Drug designations by the FDA. It is a CD22-directed antibody—drug conjugate available as a 0.9-mg lyophilized powder in a single-dose vial for reconstitution and further dilution by IV administration. The recommended dosing regimen for cycle 1 and subsequent cycles is dependent on the patient’s response to treatment as outlined in the dosage and administration section of the prescribing information.

	On August 30, 2017, Kymriah (tisagenlecleucel) was approved by the FDA for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. Kymriah is a CD19-directed genetically modified autologous T-cell immunotherapy available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Kymriah REMS, because of the risks of cytokine release syndrome and neurological events associated with the medication. The FDA granted the drug Priority Review and Breakthrough Therapy designations. It is available in single-dosed units containing 0.2 to 5.0 × 106 chimeric antigen receptor (CAR)—positive viable T cells per kg of body weight for patients 50 kg or less. For patients weighing more than 50 kg, single-dose units containing 0.1 to 2.5 × 108 CAR-positive viable T cells are available. Kymriah is to be administered intravenously via patient-specific infusion bags.

	On September 1, 2017, Mylotarg (gemtuzumab ozogamicin) was approved by the FDA for the treatment of newly diagnosed CD33-positive AML in adults and the treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older. Mylotarg is a CD33-directed antibody—drug conjugate that was granted Orphan Drug designation for its indications. It originally received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse. Mylotarg was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths. The September 2017 approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population. Mylotarg is available as a 4.5-mg lyophilized cake or powder in a single-dose vial for IV administration. The recommended dose of Mylotarg is dependent on the disease state and treatment experience, which is available in the prescribing information.

	On September 14, 2017, Aliqopa (copanlisib) was approved for the treatment of adults with relapsed FL who have received at least 2 prior treatments known as systemic therapies. Continued approval for this indication of Aliqopa—which was granted accelerated approval&mdash;may be contingent on verification and description of clinical benefit in a confirmatory trial. The drug also received Priority Review and Orphan Drug designations by the FDA. Aliqopa is a kinase inhibitor available in a 60-mg single-dose lyophilized solid vial for reconstitution. The recommended dose is 60 mg administered as a 1-hour IV infusion on days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (3 weeks on and 1 week off).

	On October 18, 2017, Yescarta (axicabtagene ciloleucel) was approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from FL. The FDA granted the drug Priority Review, Breakthrough Therapy, and Orphan Drug designations. It is a CD19-directed genetically modified autologous T-cell immunotherapy available as a cell suspension for infusion. CAR-positive viable T-cell therapy is manufactured specifically for each individual patient. Yescarta’s availability and target dose is 2 × 106 CAR-positive viable T cells per kg of body weight, with a maximum of 2 × 108 CAR-positive viable T cells in approximately 68 mL. Because of the risk of cytokine release syndrome and neurologic toxicities, Yescarta was approved with a REMS. It is to be administered in a certified health care facility.

	On October 31, 2017, Calquence (acalabrutinib) was approved by the FDA for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent on verification and description of clinical benefit in confirmatory trials. The FDA granted the drug Priority Review, Breakthrough Therapy, and Orphan Drug designations. Calquence is a kinase inhibitor available in a 100-mg capsule. The recommended dose is 100 mg orally approximately every 12 hours until disease progression or unacceptable toxicity. Calquence capsules can be swallowed whole with water and with or without food.

	On July 17, 2017, Nerlynx (neratinib) was approved by the FDA for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor 2 (HER2)—overexpressed/amplified breast cancer to follow adjuvant trastuzumab-based therapy. Nerlynx is a kinase inhibitor available in a 40-mg tablet. The recommended dose is 240 mg (6 tablets) given orally once daily with food, continuously for 1 year. Antidiarrheal prophylaxis is recommended during the first 2 cycles (56 days) of treatment and should be initiated with the first dose.

	On March 13, 2017, Kisqali (ribociclib) was approved by the FDA for the combination treatment of postmenopausal women with hormone receptor (HR)—positive, HER2-negative advanced or metastatic breast cancer. The FDA granted this application Priority Review and Breakthrough Therapy designations. Kisqali is a kinase inhibitor available as a 200-mg tablet. The recommended starting dose is 600 mg orally (three 200-mg tablets) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days. Kisqali should be coadministered with letrozole 2.5 mg once daily throughout the 28-day cycle.

	On September 28, 2017, Verzenio (abemaciclib) was approved in combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. Verzenio was also approved as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. Verzenio is a selective ATP-competitive inhibitor of cyclin-dependent kinases 4 and 6. It is available for oral use in 50-, 100-, 150-, and 200-mg tablets. The recommended starting dose in combination with fulvestrant is 150 mg twice daily, and the starting dose as monotherapy is 200 mg twice daily with or without food.

	On December 1, 2017, Ogivri (trastuzumab-dkst) was approved as a biosimilar to Herceptin for the treatment of patients with breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma) whose tumors overexpress the HER2 gene (HER2-positive). Ogivri is a HER2/neu receptor antagonist. Patients are selected for therapy based on an FDA-approved companion diagnostic for a trastuzumab product. It is not to be substituted for or with ado-trastuzumab emtansine. Ogivri is available as a 420-mg lyophilized powder in a multidose vial for reconstitution. It is to be administered as an IV infusion over 90 minutes. Please refer to the prescribing monograph for detailed information regarding doses and treatment schedules.

	On March 23, 2017, Bavencio (avelumab) was approved by the FDA for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma. The FDA granted the drug Priority Review, Breakthrough Therapy, and Orphan Drug designations. Furthermore, on May 9, 2017, Bavencio received an expanded indication by the FDA for the treatment of patients with locally advanced or metastatic 

 whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. The above indications were granted accelerated approval based on tumor response and duration of response. Continued approval of the above indications may be contingent on verification and description of clinical benefit in confirmatory trials. Bavencio is an antibody that blocks programmed death-ligand 1 (PD-L1) and is available as a 200-mg/10-mL (20 mg/mL) solution in a single-dose vial for IV use. The recommended dose is 10 mg/kg as an IV infusion over 60 minutes every 2 weeks.

	On March 27, 2017, Zejula (niraparib) was approved by the FDA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Zejula is a poly ADP-ribose polymerase (PARP) inhibitor available as 100-mg capsules. It was the first PARP inhibitor to be approved by the FDA that does not require BRCA mutation or other biomarker testing. The FDA granted this application Fast Track, Priority Review, and Breakthrough Therapy designations, as well as Orphan Drug designation specifically for treating recurrent epithelial ovarian cancer. The recommended dose is 300 mg taken once daily with or without food.

	On April 28, 2017, Alunbrig (brigatinib) was approved by the FDA for the treatment of patients with anaplastic lymphoma kinase—positive metastatic NSCLC who progressed on or are intolerant to crizotinib. This indication was granted accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent on verification and description of clinical benefit in a confirmatory trial. Alunbrig is a kinase inhibitor available as 30- and 90-mg tablets. The recommended dose is 90 mg orally once daily, with or without food, for the first 7 days. If tolerated, the dose may be increased to 180 mg orally once daily.

	On May 1, 2017, Imfinzi (durvalumab) was approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had disease progression during or following platinum-containing chemotherapy or who had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication was granted accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent on verification and description of clinical benefit in confirmatory trials. Imfinzi is a PD-L1—blocking antibody available as a 500-mg/10-mL (50 mg/mL) or 120-mg/2.4-mL (50-mg/mL) solution in a single-dose vial for IV use. The recommended dose is 10 mg/kg as an IV infusion over 60 minutes every 2 weeks.

	On September 14, 2017, Mvasi (bevacizumab-awwb), a biosimilar to Avastin (bevacizumab), received FDA approval for the treatment of multiple types of cancer: metastatic colorectal cancer, with IV 5-fluorouracil—based chemotherapy for first- or second-line treatment; metastatic colorectal cancer, with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product–containing regimen; nonsquamous NSCLC, with carboplatin and paclitaxel for first-line treatment of unresectable, locally advanced, recurrent, or metastatic disease; glioblastoma, as a single agent for adult patients with progressive disease following prior therapy; metastatic renal cell carcinoma with interferon alpha; and cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease. Mvasi is an anti–vascular endothelial growth factor A monoclonal antibody. It is to be administered only as an IV infusion and not to be initiated for 28 days following a major surgery and until surgical wounds are fully healed. The first infusion is to be administered over 90 minutes, and subsequent infusion times can range from 30 to 60 minutes depending on patient tolerability to first infusion. Recommended dosing and scheduling vary depending on indication. Mvasi is available as a 100-mg/4-mL or 400-mg/16-mL single-dose vial of preservative-free solution.

	On November 9, 2017, the FDA approved Cinvanti (aprepitant) in combination with other antiemetic agents for the prevention of acute and delayed nausea and vomiting in adults associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC), including high-dose cisplatin, and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). Cinvanti is a substance P/neurokinin-1 receptor antagonist available as a 130-mg injectable emulsion in a single-dose vial. The recommended dose in adults for HEC (single-dose regimen) is 130 mg on day 1 as an IV infusion over 30 minutes approximately 30 minutes prior to chemotherapy. The recommended dosage in adults for MEC (3-day regimen) is 100 mg administered on day 1 as an IV infusion over 30 minutes approximately 30 minutes prior to chemotherapy, and aprepitant capsules (80 mg) are given orally on days 2 and 3. Cinvanti is part of a regimen that includes a corticosteroid and a serotonin type 3 antagonist.

Additional Late-Breaking Specialty FDA Actions

	On October 13, 2017, Stelara (ustekinumab) received an expanded indication for the treatment of adolescents (12 years and older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Stelara is a human interleukin-12 and -23 antagonist that was originally approved in September 2009. It is also indicated for the treatment of adult patients with moderate to severe psoriasis who are candidates for phototherapy or systemic therapy; active psoriatic arthritis (PsA), alone or in combination with methotrexate; and moderately to severely active Crohn disease who have failed or were intolerant to treatment with immune modulators or corticosteroids but who never failed a tumor necrosis factor (TNF) blocker or who failed or were intolerant to treatment with 1 or more TNF blockers. Stelara is available as a subcutaneous injection in a 45-mg/0.5-mL or 90-mg/mL single-dose prefilled syringe and a 45-mg/0.5-mL single-dose vial. It is also available as an IV infusion in a 130-mg/26-mL (5-mg/ml) solution in a single-dose vial. The recommended dose for adolescent patients with moderate to severe psoriasis is weight based, and doses are administered subcutaneously at weeks 0 and 4 and then every 12 weeks thereafter.

	On October 20, 2017, Simponi Aria (golimumab) received an expanded indication by the FDA for the treatment of adult patients with active PsA or active 

 (AS). Simponi Aria is a TNF blocker that was originally approved in July 2013. It is also approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis in combination with methotrexate. The recommended dose is a 2 mg/kg IV infusion over 30 minutes at weeks 0 and 4 and then every 8 weeks. For patients with PsA or AS, Simponi Aria may be given with or without methotrexate or other nonbiologic disease-modifying antirheumatic drugs. Corticosteroids, nonsteroidal anti-inflammatory drugs, and/or analgesics may be continued during treatment. Simponi Aria is available as a 50-mg/4-mL (12.5-mg/mL) solution in a single-use vial.

	On October 23, 2017, Soliris (eculizumab) received an expanded indication for the treatment of patients with generalized myasthenia gravis (gMG) who are anti—acetylcholine receptor antibody–positive. Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris. Therefore, it is available only through a restricted program under a REMS. Soliris is a complement inhibitor that was first approved in March 2007. It is also indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria to reduce hemolysis and the treatment of patients with atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy. Soliris is not indicated for the treatment of patients with hemolytic uremic syndrome related to Shiga toxin–producing Escherichia coli. The recommended dose for patients with gMG is 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, and then 1200 mg every 2 weeks thereafter. Soliris should be administered at the recommended dosage regimen time points or within 2 days of these time points. Soliris is available as a 300-mg/30-mL (10-mg/mL) solution in a single-dose vial for injection.

	On November 14, 2017, Fasenra (benralizumab) was approved by the FDA as an add-on maintenance treatment for patients with severe asthma 12 years and older and with an eosinophilic phenotype. Fasenra is an interleukin-5 receptor, alpha-directed cytolytic monoclonal antibody. It is available as a 30-mg/mL solution in a single-dose prefilled syringe for subcutaneous injection. The recommended dose is 30 mg every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter.

	On November 15, 2017, the FDA approved Mepsevii (vestronidase alfa) for the treatment of mucopolysaccharidosis VII (Sly syndrome) in pediatric and adult patients. The FDA granted Mepsevii Fast Track and Orphan Drug designations and a rare pediatric disease priority review voucher for this approval. It is a recombinant human lysosomal beta glucuronidase available in a 10-mg/5-mL (2-mg/mL) single-dose vial for intravenous use. The recommended dose is 4 mg/kg administered every 2 weeks as an intravenous infusion over approximately 4 hours.

	On November 16, 2017, Hemlibra (emicizumab-kxwh) was approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors. The FDA granted Hemlibra Priority Review, Breakthrough Therapy, and Orphan Drug designations for this approval. It is a bispecific factor IXa— and factor X–directed antibody available in 30-mg/mL, 60-mg/0.4 mL, 105-mg/0.7 mL, and 150-mg/mL single-dose vials for subcutaneous use. The recommended dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.

	On November 21, 2017, Juluca (dolutegravir and rilpivirine) was approved as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca. Juluca is a 2-drug combination of dolutegravir, an HIV-1 integrase strand transfer inhibitor, and rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor. It is available as a tablet formulation consisting of 50 mg of dolutegravir (equivalent to 52.6 mg dolutegravir sodium) and 25 mg of rilpivirine (equivalent to 27.5 mg rilpivirine hydrochloride). The recommended dose is 1 tablet taken orally once daily with a meal.

	On November 29, 2017, Isentress (raltegravir) received an expanded approval by the FDA for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients weighing at least 2 kg. Isentress is an HIV integrase strand transfer inhibitor. It was originally approved in October 2007 for the treatment of adults with HIV-1 infection in combination with other antiretroviral agents. Isentress is available as 400- and 600-mg film-coated tablets, 100-mg scored and 25-mg chewable tablets, and 100-mg single-use packets for oral suspension. Please refer to the prescribing monograph for weight-based dosing for pediatric patients.

	On December 1, 2017, Repatha (evolocumab) received an expanded indication by the FDA to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease and is to be used as an adjunct to diet, alone, or in combination with other lipid-lowering therapies (eg, statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C).Repatha is a proprotein convertase subtilisin/kexin type 9 inhibitor antibody originally approved in August 2015. It is also indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C. Repatha is available as a single-use 140-mg/mL prefilled SureClick autoinjector or a prefilled syringe and as a 420-mg/3.5-mL solution in a single-use Pushtronex system for subcutaneous use that patients can self-administer. The recommended dosage for adults with established cardiovascular disease or primary hyperlipidemia (including heterozygous familial hypercholesterolemia) is 140 mg every 2 weeks or 420 mg once monthly subcutaneously in the abdomen, thigh, or upper arm.

	On December 1, 2017, Taltz (ixekizumab) received an expanded indication by the FDA for the treatment of adults with PsA. Taltz is a humanized interleukin-17A antagonist that was first approved in March 2016 for the treatment of adults with moderate to severe plaque Ps who are candidates for systemic therapy or phototherapy. Taltz is available as a subcutaneous injection in a prefilled auto-injector or as a single-dose prefilled syringe containing 80 mg/mL. The recommended starting dose for PsA is 160 mg (two 80 mg subcutaneous injections) at week 0, followed by 80 mg every 4 weeks. Taltz may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (eg, methotrexate).

	On December 12, 2017, Nucala (mepolizumab) received an expanded approval by the FDA for treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). The FDA granted it Priority Review and Orphan Drug designations for this indication. Nucala was first approved in November 2015 as an add-on maintenance treatment for patients with severe asthma 12 years and older and with an eosinophilic phenotype. It is a humanized interleukin-5 antagonist monoclonal antibody (IgG1 kappa) that is available in a single-dose vial containing 100 mg of lyophilized powder for reconstitution. Nucala is not to be used for treatment of other eosinophilic conditions and not for relief of acute bronchospasm or status asthmaticus. The recommended dose for EGPA is 300 mg as 3 separate 100-mg injections administered subcutaneously once every 4 weeks by a health care professional into the upper arm, thigh, or abdomen as detailed in the prescribing information.

	On December 13, 2017, Ixifi (infliximab-qbtx) was approved by the FDA as a biosimilar to Remicade. The FDA has approved Ixifi as a treatment for patients with rheumatoid arthritis, Crohn disease, pediatric Crohn disease, ulcerative colitis, AS, PsA, and plaque psoriasis. It is a TNF blocker available as 100 mg of lyophilized infliximab-qbtx in a 15-mL vial for intravenous infusion over a period of not less than 2 hours. Refer to the prescribing monograph for information regarding disease-specific dosage details.

	On December 19, 2017, Luxturna (voretigene neparvovec-rzyl) received FDA approval for the treatment of patients with confirmed biallelic RPE65 mutation—associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician(s). Luxturna received Priority Review, Breakthrough Therapy, and Orphan Drug designations for this approval. It is an adeno-associated virus vector-based gene therapy available as a suspension for subretinal injection, supplied in a 0.5-mL extractable volume in a single-dose 2-mL vial for a single administration in 1 eye. The supplied concentration (5 × 1012 vg/mL) requires a 1:10 dilution prior to administration. The recommended dose for each eye is 1.5 × 1011 vector genomes, administered by subretinal injection in a total volume of 0.3 mL. Subretinal administration should be performed to each eye on separate days within a close interval, with at least 6 days between surgical procedures. It is also recommended to give systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (maximum of 40 mg/day) for a total of 7 days (starting 3 days before administration of Luxturna to each eye), followed by a tapering dose during the following 10 days.

The second part of a comprehensive review of the specialty pharmaceuticals approved by the FDA in 2017. 

Specialty Drugs: Year in Review 2017 Part II

	In response to the numerous concerns regarding antineoplastic drugs and other medications that may threaten the health of patients and health care workers, the National Institute for Occupational Safety and Health (NIOSH) developed a list, updated biennially, of hazardous drugs. Cancer chemotherapy, antivirals, and hormone therapies are only some of drugs listed in the 2016 NIOSH list.

	NIOSH classifies hazardous drugs as those that exhibit any of the following 6 characteristics in humans or animals: 

	A key takeaway is that because NIOSH classifies hazardous drugs based on the 1990 definition provided by the American Society of Hospital Pharmacists (ASHP, now known as the American Society of Health-System Pharmacists), the institute may not accurately classify newer pharmaceuticals, such as bioengineered drugs that are target specific. Moreover, NIOSH has not attempted to perform risk assessments on each drug or determine exposure limits.

	NIOSH groups hazardous drugs into 3 categories (

) that are primarily focused on classifying the potential for reproductive and developmental toxicity, based on the needed dose to produce toxicity in animals and/or whether adverse effects are observed in animals at or near the maximum recommended human dose.

	Three tables in the 2016 list outline the hazardous drugs and their properties, compiled from the updated 2014 NIOSH list of hazardous drugs and the 2016 update, which included 34 new drugs (

). There were no deletions from the 2014 list.

	 The NIOSH tables include a Supplemental Information column, which describes potential black box warnings and/or the FDA pregnancy category. Although the FDA removed the pregnancy letter categories for prescription labeling in 2015, the 2016 NIOSH list continues to use the that lettering system.

 Most of the drugs categorized as X and D meet the ASHP criteria for hazardous drugs and are recorded in the 2016 NIOSH list.

	The FDA definitions of the 2 most prevalent categories are as follows in 

	NIOSH recommends that in addition to using the information provided in the 2016 list of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, organizations create their own list based on their formulary.

 The third section of the NIOSH alert provides detailed information on how to create a hazardous drug list.

	Health care personnel must be aware of the risk of altering formulations. Coated tablets or capsules that are administered without modification may not pose a hazard, but if they are crushed or placed in an automated counting machine, the dust that results may pose a risk via inhalation or skin contact.

	Overall, approximately 8 million US health care workers are potentially subjected to the risks of hazardous drugs; moreover, the use of antineoplastic agents and drugs is increasing quickly. It is imperative that organizations identify the hazardous drugs on their formulary, as well as implement procedures and policies that protect their patients and workers.

		The National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. Centers for Disease Control and Prevention website. cdc.gov/niosh/docket/review/docket233a/pdfs/2016-161finalpublication.pdf. Published September 2016. Accessed June 22, 2017.

		US Food and Drug Administration. Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, 73 Fed. Reg. 30831-68 (May 29, 2008).

		The National Institute for Occupational Safety and Health. Hazardous drug exposures in health care. Centers for Disease Control and Prevention website. cdc.gov/niosh/topics/hazdrug/default.html. Updated August 25, 2017. Accessed July 6, 2017.

Chemotherapy, antivirals, and hormone therapies are among the drugs addressed in the 2016 National Institute for Occupational Safety and Health list.

Key Points From the 2016 NIOSH List of Antineoplastic and Hazardous Drugs in Health Care Settings

	Nearly half of patients taking medications for chronic disease discontinue the drugs or do not take them as prescribed, according to the FDA. While these treatments can help patients who take them properly, many have narrow pharmacokinetic and adverse effect profiles. As a result, poor adherence increases the risk of complications and worsens outcomes for patients. 

	Nonadherence and therapy discontinuation contribute to more than 125,000 deaths and cost the United States between $100 billion and $300 billion annually, according to the CDC. The specialty pharmaceutical industry, expected to account for 50% of all medication spending in the United States by 2020, according to a report by McKesson Corporation, is increasingly feeling the pain of the adherence epidemic. 

High Discontinuation of Specialty Pharmaceuticals Remains a Struggle 

	Given the high cost of specialty drug treatments, maximizing their efficacy is paramount. Scrutiny of drug pricing is near the top of the national discourse and is a priority for specialty manufacturers and pharmacies alike to help ensure that these treatments yield their publicized results. 

	Yet for many specialty pharmaceuticals, the discontinuation curve, a measure of how many patients prematurely stop taking their prescribed medication, can jeopardize outcomes. The fact is, for certain specialty therapies, up to 30% of patients discontinue medication within the first 90 days of treatment.  

	Specialty pharmacies can play an important role in minimizing discontinuation and helping patients adhere to their medication, but their approach to patient support and follow-up is often archaic. Historically, pharmacies have employed nurse call centers to place cold follow-up calls with customers. 

	These nurse support teams are typically expected to manage compliance without any knowledge of the patient’s activity after a prescription has been filled. That means specialty pharmacies are providing patient support while effectively blindfolded. 

	Frequently, patients who are taking their medications as prescribed are telephoned unnecessarily. At the same time, patients who are not adhering to their regimen are often not called after the first or second missed dose. This results in suboptimal allocation of resources and missed opportunities to intervene at critical moments—before patients enter the discontinuation curve. 

	Until now, specialty pharmacies have had limited or delayed visibility into their customers’ dosing habits and into the behaviors that result in poor medication adherence, such as procrastination, forgetfulness, and fear of adverse effects.  

Intelligence Can Transform Specialty Pharmaceutical Support

	Today, new paradigms and technologies can better support specialty pharmacy adherence programs. When armed with intelligent touch points, specialty pharmacies can connect with patients before they drift from proper habits. They can also prevent intrusion into the lives of patients who are taking their medications as prescribed. 

	Technology-driven customer intelligence and analytics helped Netflix transform the customer experience of media consumption by recording and analyzing viewing habits and applying them to make highly targeted recommendations. By pairing a smart technology strategy with support interventions, specialty pharmacies can also transform their customer support experience. When they apply real-time intelligence about medication utilization, specialty pharmacies can engage the right patients with the right message at the right time. This leads to more return on the investment in customer support and lower discontinuation. Right-time engagement improves outcomes for patients, efficiencies for pharmacies, and the bottom-line for everyone.   

Smart Medication Adherence Technology Can Deliver Actionable Intelligence

	How do specialty pharmacies gain customer intelligence? They can use smart medication adherence technology: internet-connected tools that offer comprehensive levels of medication monitoring and control, both for patients and for those who support them.

	A broad array of technologies now exists to remind patients when to take their medication and record their behavior. There is a large variation in feature sets and capabilities of this technology. If you are considering adding technology to enhance your patient support experience—and you should&mdash;it’s important to choose a comprehensive solution that includes customizable clinical, behavioral, and analytical tools.

5 Components Your Medication Adherence Technology Must Have

	Here are essential areas to look for in a smart medication adherence technology solution:

	To be effective, adherence technology should work right out of the box and not have many asks from the patient. Patients should not be required to set up a device or download an application. Implementation should also be easy and unobtrusive for the pharmacy. For example, the technology should integrate automatically with standard pharmaceutical packaging so that it does not conflict with dispensing workflows. Analytics software should be simple to connect to existing databases and intuitive to use. Solutions that offer both desktop and mobile access across all technology platforms and operating systems are the most flexible. Two-way communication between support team members and the patient is essential. 

2. Comprehensive, actionable patient insight.

	The most effective solutions not only track and gather data on medication access and usage but also organize the metrics in a way that maximizes visibility and facilitates action for support team members. The analytical tool should be flexible enough to aggregate and display behavioral data by multiple views and categories, including individual patient, geography, and therapy class. Detailed dosing logs should be viewable in graph or list form. Communications and notes (by support team members) should be automatically added to the analytics. For reporting flexibility, a tool that integrates automatically with Excel, Word, and PDFs is ideal. Aggregate reporting of real-life dispensation and adherence patterns can be shared with drug manufacturers and may facilitate outcomes-based contracting.

	An adherence technology solution must be highly configurable to meet the unique needs of your organization and your patient population. For example, you should be able to set and adjust different patient reminder alert preferences, including visual and audio reminders. Support teams should also be able to customize how they receive alerts on their end, whether it be by e-mail, text, or phone. A configurable, rules-based triage notification/escalation system facilitates timely follow-up and intervention. The analytics software should also be customizable, with flexible and adaptable information displays. 

	Smart adherence technology should not only record all data about medication dispensation but also deliver the information in real time to notify support team members of opportunities to intervene. For example, if the pharmacy identifies 2 missed doses as an intervention threshold, the support team should receive an alert in real time as soon as a patient misses the second dose so that the team can take the right action in a timely manner.

	Be sure that your technology solution is robust and protected with a 21 CFR Part 11—validated system that is compliant with the Health Insurance Portability and Accountability Act of 1996.

	Here’s an example of a scenario in which a specialty pharmacy can apply smart medication adherence technology to engage with patients before they discontinue therapy:

	1. The specialty pharmacy or patient support program enrolls the patient in a medication adherence technology—enhanced program.

	2. The specialty pharmacy dispenses to the patient the first prescription fill, which includes data capture and alert technology built into the medication packaging.

	3. The patient is alerted with a reminder to take a dose as prescribed through a visual or audio cue and reminded to eat a meal before dosing, if advised.

	4. The patient takes a dose on time. The dosage data are recorded and transmitted securely to the support team’s database and analytic tool and captured for reporting.

	5. The patient misses a dose or reports undesirable symptoms after taking a dose. This information is sent in real time as a notification to the support team members via the communication method they selected as their preferred medium.

	6. A support team member sends a personalized message to the patient via the portal, or calls them, to discuss and resolve the challenge before it magnifies. 

	Health care organizations that have incorporated smart technology into their patient support programs have seen their average medication adherence improve from 75% or less to 95% or more. If you’re ready to improve your persistency curves, optimize your patient support, and improve your patient outcomes, it’s time to add intelligence and analytics to the medication adherence equation.

Moses Zonana attended Rutgers University and obtained his B.A. in Mathematics. In 2005, he earned his MBA from Harvard Business School with academic honors. With more than 15 years of executive-level experience, Zonana used his diverse expertise in healthcare, telecommunications and technology to develop Compliance Meds Technologies (CMT), a health technology solutions provider that offers patient-centric, enterprise-grade solutions that empower personalized and coordinated medication adherence interventions and patient engagement.

Technology-driven customer intelligence and analytics allowÂ specialty pharmacies to connect with patients before they drift from proper habits.

Transform Patient Support: 5 Components Your Medication Adherence Technology Must Have

	Each year, more health systems and academic medical centers implement in-house specialty pharmacy programs. According to the 2016 American Society of Health-System Pharmacists (ASHP) survey of hospital pharmacy practice, a specialty pharmacy operation is in place in 47.1% of hospitals with 600 or more staffed beds. The percentage declines with hospital size, down to 1.6% of hospitals with fewer than 50 beds.

	Whether a hospital is a community hospital, part of a larger health system, or the flagship of an academic medical center, it should address the issue of specialty pharmacy in all its operational and economic complexity. However, just 8.7% of all hospitals surveyed operate a specialty pharmacy.

	When planning for a specialty pharmacy within a health system, 3 business models should be considered: build, partner, and outsource. A fourth model—doing nothing or delaying a decision&mdash;becomes, by default, a fragmented, reactive outsourcing program with individual patient risk managed as it arises. And it is bound to arise.

	As specialty drugs carve out a greater slice of the pharmaceutical landscape, delaying a decision leaves the health system at a disadvantage in terms of managing the cost of care, maintaining continuity of care, managing medical records, delivering a high-quality experience for patients and their families, and retaining pharmacy revenue.

	A brief description of each model follows. Organizations should consider the business case for and against each one: What are its advantages and disadvantages? What is the risk involved in following or not following this pathway? What resources would be required?

	A health system is best positioned to successfully implement an in-house specialty pharmacy operation if it has 3 things:

		Existing ambulatory pharmacy capabilities

	The largest health systems and those with many specialty patients, such as academic medical centers, will see the clearest potential from building their own capabilities. The build model’s greatest benefit is the ability to manage care and transitions of care seamlessly, so that complex patients continue to receive their medications. The deciding factor in getting in or staying out is likely to be economic. Many health systems may choose to enter the space, regardless of the economic return, to align pharmacy services with their institutional mission and values.

	An existing ambulatory pharmacy operation reduces the risk of issues during care transitions and provides a head start in terms of infrastructure and expertise. However, specialty pharmacy operations differ from traditional ambulatory pharmacy in many ways. Technology platforms, strict storage and dispensing capabilities, call center capabilities, and shipping capabilities will likely need to be developed.

	Building a specialty pharmacy program can be approached incrementally or all at once. Either way, it is important to recognize that a capability intended to serve as much of the organization as possible from inception may still have to accommodate payers and products to which the organization does not have access. Any related concerns about access to product and access to patient lives should not, however, delay implementation. As an organization’s specialty pharmacy grows, develops, and consistently meets patient, manufacturer, and prescriber expectations, it will become more likely to gain access to these contracts.

	Another option that can permit health systems to retain some of the advantages of controlling their own specialty pharmacy function, depending on the choices made, is the partner model.

	Midsize health systems or those with a lower concentration of specialty patients may be best served by developing some functions in-house and finding partners to assist with the rest.

	Partnerships allow health systems to tap into expertise, technology, and manufacturer relationships that could be prohibitively difficult to develop on their own. As the business plan is reevaluated every few years, the decision can be made to pivot to an in-house operation. Avera Health System in South Dakota, for example, subcontracted call center services to Fairview Specialty Pharmacy while building its own specialty pharmacy. 

	If a health system sees compelling reasons to offer a full range of specialty pharmacy services, it may also see value in partnering or contracting with an outside resource or resources to provide certain services and perhaps accelerate speed to market. Partners are available to manage call centers, run prior authorization and patient assistance programs, provide staff training and education on the latest therapies, and take on many other aspects of the operation. Personnel needs will be less than in a full build-out, an advantage to organizations that have limited resources to acquire staff or that struggle with finding qualified employees. 

	The partner model allows the health system to leverage its strengths and bring in aligned resources to fill out its capabilities. Assembling the pieces involves considerable complexity, but a number of organizations have done so successfully. 

	With the outsource model, an organization contracts out all or most of the services, including fulfillment or patient care, that an in-house specialty pharmacy (or partner) would otherwise provide. Wholesaler subsidiaries and group purchasing organizations may offer the solutions a health system needs to put this model into place. Multiple vendors may be required to cover a range of specialty pharmaceuticals, or the selected vendor may have collaborative arrangements with other companies. Vendors frequently offer co-branding opportunities, placing the health system’s name and logo on prescription labels and promotional materials. 

	The outsource model makes continuity of care challenging; therefore, health systems should develop processes that help coordinate care as much as possible. 

Opportunities inside and outside health systems

	In the larger specialty pharmacy marketplace, businesses such as Shields Health Solutions, Trellis Rx, and Acentrus Specialty, as well as organizations such as Excelera, have emerged to help health systems negotiate the complexities of planning, funding, building, and operating successful specialty pharmacies. Large specialty pharmacies such as Diplomat, among others, also provide a variety of services to help fill partnership or outsourcing needs.

	For manufacturers, payers, large specialty pharmacies, technology providers, and others, conversations that recognize the mission-driven nature of health systems and acknowledge the often-challenging economic realities they face can be the first step toward effective collaboration, whichever model a health system seeks to implement. 

	Many of the largest health systems and major academic medical centers recognize the significant clinical and economic benefits of pursuing the specialty pharmacy build model. Other health systems generally fall into 2 categories: 

		Leadership has decided to pursue specialty pharmacy through a partnership or outsourcing agreement, a path that usually makes sense for mid-size health systems.

		Leadership is focused on other pressing issues, with specialty pharmacy planning falling to the bottom of a long list of concerns. 

	For those who have failed to engage with the topic, the time to do so is now. An excellent resource for further information is the ASHP Specialty Pharmacy Resource Guide, available for download at 

		Pederson, Craig A et al. ASHP national survey of pharmacy practice in hospital settings: Prescribing and transcribing — 2016. 

When planning for a specialty pharmacy within a health system, 3 business models should be considered: build, partner, and outsource.

Indecision Is Not an Option: Understanding the Range of Business Models for Health-System Specialty Pharmacy

	The FDA had approved 35 new specialty medications in 2017 at the time of this writing. This is more than twice as many specialty approvals as in 2016 (17) and tops the 33 specialty drugs approved in 2015. In the second half of 2017 alone, FDA-approved specialty drugs included several cancer therapies, a biologic for psoriasis, 2 pan-genotypic (genotypes 1-6) hepatitis C virus (HCV) drugs, and a novel hemophilia medication.

	The FDA approved 14 new cancer medications in 2017, including 2 chimeric antigen receptor (CAR) T-cell therapies,

. In CAR T-cell therapy, some of the patient’s T cells are removed, modified to target the CD19 antigen expressed by certain cancer cells, and then infused back into the patient. Kymriah was approved on August 30 to treat patients younger than 25 who have B-cell acute lymphoblastic leukemia that relapsed at least twice or who are no longer responding to standard treatments. Yescarta was approved on October 18 to treat adult patients with relapsed or refractory forms of non-Hodgkin lymphoma that has been treated at least twice with other drugs. Kymriah and Yescarta are very effective therapies that are given as 1-time intravenous (IV) infusions. Both drugs have concerning adverse effects, including severe neurologic events and cytokine release syndrome, which need to be closely monitored. Kymriah costs $475,000 per treatment regimen, and Yescarta costs $373,000 per treatment regimen.

 was approved on July 13 for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Tremfya is a biologic in a new class of medications that inhibit interleukin-23 (IL-23). After induction dosing, it is administered every 8 weeks via subcutaneous (SC) injection. Tremfya demonstrated improved skin clearance compared with Humira (adalimumab) in 2 late-phase studies. Sun Pharmaceuticals’ tildrakizumab is another IL-23 inhibitor that is in development for psoriasis. After induction dosing, it is administered every 12 weeks via SC injection. Tildrakizumab has demonstrated improved skin clearance compared with Enbrel (etanercept). Approval of tildrakizumab is expected by March 24, 2018.

Vosevi (sofosbuvir/velpatasvir/voxilaprevir)

 are new pan-genotypic drugs that were approved for HCV on July 17 and August 3, respectively. Vosevi was approved for the re-treatment of chronic HCV infection in adults with genotype 1, 2, 3, 4, 5, or 6 previously treated with an NS5A inhibitor—containing regimen or in adults with genotype 1a or 3 previously treated with a sofosbuvir-containing regimen without an NS5A inhibitor. The recommended dose of Vosevi is 1 tablet once daily for 12 weeks. Mavyret was approved for the initial treatment of patients infected with HCV genotypes 1 to 6 without cirrhosis or with compensated cirrhosis. It was also approved for the treatment of adult patients with HCV genotype 1 who were previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor but not both. The recommended dose of Mavyret is 3 tablets once daily with food for 8, 12, or 16 weeks, depending on which (if any) medications the patient has previously tried and whether the patient has compensated cirrhosis. Vosevi costs $74,760 for the 12-week regimen, and Mavyret costs $39,600 for the 12-week regimen.

	On November 16, the FDA approved Genentech’s 

 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A who have developed antibodies called factor VIII inhibitors. It is a Breakthrough Therapy that was approved 3 months ahead of schedule. Hemophilia A is a rare, chronic, genetic bleeding disorder affecting approximately 16,000 adults and children in the United States. It is caused by insufficient activity of clotting factor VIII, a protein in the blood that controls bleeding.

	Patients with hemophilia A experience bleeding episodes that cause pain, irreversible joint damage, and possible life-threatening hemorrhages. An estimated 1 in 3 persons with severe hemophilia A develops factor VIII inhibitors or antibodies to the factor VIII replacement therapies. The presence of these inhibitors can result in an increased risk for life-threatening bleeds or repeated bleeds. Hemlibra is a bispecific monoclonal antibody that replaces the activity of coagulation factor VIII by sticking to both activated coagulation factor IXa and factor X to prevent bleeding episodes for patients who have hemophilia A and inhibitors to factor VIII. Hemlibra is administered as a once-weekly SC injection. The cost depends on the patient’s weight. However, at an average patient weight of 127 pounds, therapy would cost approximately $482,000 for the first year of treatment and approximately $448,000 per year thereafter. 

	In 2018, watch for more cancer drugs to affect the market (

). In addition, several new orphan drugs and the first calcitonin gene-related peptide (CGRP) inhibitors for migraine are expected to gain approval. More information about select specialty pipeline medications follows.

	Janssen’s apalutamide is an oral androgen receptor inhibitor that is pending approval for the treatment of men with nonmetastatic castration-resistant prostate cancer (CRPC). Prostate cancer is diagnosed in approximately 161,000 men each year in the United States. Up to 20% of these patients may develop CRPC within 5 years of diagnosis. Currently, no drugs are approved for nonmetastatic CRPC; however, Xtandi (enzalutamide), from Astellas and Medivation, may receive this expanded approval in the second half of 2018. Approval of apalutamide is expected by April 10, 2018. 

	Bayer and Loxo Oncology’s larotrectinib is an oral tropomyosin receptor kinase (TRK) inhibitor that is in development for the treatment of unresectable or metastatic solid tumors with neurotrophic TRK fusion proteins in adult and pediatric patients who require systemic therapy and who either have progressed following prior treatment or have no acceptable alternative treatments. TRK fusion proteins are present in only approximately 3% of cancer cases; however, they are more common in certain hard-to-treat cancers of the appendix, gallbladder, pancreas, salivary glands, and thyroid. There are between 1500 and 5000 new cases of advanced TRK fusion cancers diagnosed each year in the United States. Larotrectinib is a Breakthrough Therapy with approval expected in the second half of 2018.

In 2018, watch for novel cancer drugs and several new orphan drugs to affect the market.

January/February

Value of Real-World Evidence in Improving Patient Outcomes in Oncology

New Therapies and the Role of Specialty Pharmacy Providers

Specialty Drugs: Year in Review 2017 Part II

Key Points From the 2016 NIOSH List of Antineoplastic and Hazardous Drugs in Health Care Settings

Transform Patient Support: 5 Components Your Medication Adherence Technology Must Have

Indecision Is Not an Option: Understanding the Range of Business Models for Health-System Specialty Pharmacy

New Treatments for Cancer, Migraines Highlight Specialty Pipeline in 2018

Top Trends for 2018 in Specialty

New Strategies Needed to Confront the Growing Diabetes Epidemic

Specialty Trends That Will Define 2018