Managing Care and Costs for Orphan Conditions

Specialty Pharmacy TimesJanuary/February 2015
Volume 6
Issue 1

The number of drugs approved for orphan conditions has increased in recent years, and specialty pharmacies play an important role in the management of therapies for patients with rare diseases.

The number of drugs approved for orphan conditions has increased in recent years, and specialty pharmacies play an important role in the management of therapies for patients with rare diseases.

Orphan drugs—those used to treat rare diseases affecting fewer than 200,000 people in the United States—account for approximately 36% of all near-term specialty pipeline drugs. The number of orphan drugs approved has increased each year:

  • In 2012, orphan drugs represented 45% (10 of 22) of specialty drug approvals
  • In 2013, orphan drugs accounted for 58% (11 of 19) of specialty drug approvals
  • In 2014, orphan drugs represented 74% (20 of 27) of specialty drug approvals

Currently, almost 7000 diseases are considered rare in the United States, and more than 400 medications have been approved with orphan status. As more is learned about these diseases and new drugs are being developed, patient populations are further divided into subtypes based on causes, genetic defects, and other aspects.

Some orphan medications may treat fewer than 100 patients nationwide. In these cases, a pharmacy may rarely, if ever, care for one of these patients. A specialty pharmacy often has the largest patient population and can leverage its clinical knowledge to ensure:

  • Standardized communication, counseling, education, and care for the patient
  • Specialized care for the patient from teams who have an in-depth understanding of the drugs, conditions, and, often, the individual patient
  • Support for physicians who may not be as familiar with these drugs

High Price Tag, Need for Specialized Care

Orphan drugs have significantly improved the quality of life and survivability of patients. However, given the tens of thousands of dollars per prescription and the rising trend in the number of approvals for orphan drugs, these medications have the potential to significantly add to the cost burden for payers if not properly managed (see Tables 1 and 2).

{Click image to enlarge}

Even with advances in drug development, orphan conditions are complex, difficult to manage, and have a huge impact on patients’ lives. Specialty pharmacies understand the complexities of caring for these patients because of their expert medication-specific care protocols and specialty-trained care teams.

Accredo’s patient care model includes proactive outreach to the patient to support administration, side effect management, adherence challenges, and experience. Many of our clinicians are dedicated to a single disease state, giving them in-depth understanding and a breadth of experience which others may lack if they seldom dispense these medications or care for rare disease patients.

Accredo also is part of the exclusive or limited distribution networks for many orphan drugs, and can provide specialized patient care support for orphan disease patient populations.

{Click image to enlarge}

Best practices Accredo has developed in caring for patients with rare diseases include:

  • Trained and dedicated teams of clinical, and when needed, nonclinical staff: The clinicians in Accredo’s Therapeutic Resource Centers are often dedicated to a single disease state and have expertise in caring for rare disease patients.
  • Dedicated customer service and benefit support teams: Because orphan drugs target small patient populations, and are often very expensive, the cost can become a limiting factor in patients receiving adequate care. Patients may lack awareness of financial aid and other programs available to them. Accredo’s expertise and intimate familiarity with these medications, and the support programs available, can help ensure patients have access to the medications they need.
  • A broad national presence of nursing staff and specialty pharmacy locations: Both are critical to ensuring patient access and availability of experienced care support.
  • Application of technology in patient care models is essential: Accredo makes extensive use of online tools, such as downloadable e-books, for patient education and counseling. Accredo also offers e-mail and text refill reminders for patients with hereditary angioedema (HAE). In some areas of specialty care, Accredo also uses predictive modeling to ensure healthier outcomes by identifying patients who may become nonadherent before they discontinue their medication.

Better patient outcomes also save money for payers by avoiding downstream costs from unnecessary hospitalizations or worsening disease symptoms. These clinicians can also monitor the therapy regimens for appropriate use of these high-cost treatments, thus reducing waste from nonevidence-based therapies. Accredo also offers various trend and utilization management strategies that help payers control their specialty trend.

Some of the conditions that will see or have seen recent approvals of new orphan drugs include cystic fibrosis (CF), HAE, and cancer.

Cystic Fibrosis

CF is the most common terminal genetic disease in the Caucasian population. This hereditary disease is caused by genetic mutations and affects about 30,000 people in the United States. There are more than 1500 identified genetic defects that lead to CF. However, only 1 in every 31 people is a carrier of a defective gene that can cause the disease.

Symptoms of CF include buildup of thick, sticky mucus that primarily affects the lungs and pancreas. People who inherit the defective genes are unable to clear the mucus and suffer from recurring lung infections, declining lung function, and nutritional deficits. The disease gets its name from the fibrosis, or scarring, that occurs with chronic lung inflammation and infection. Related comorbidities include poor growth, CF-related diabetes, pancreatitis, male sterility, depression, and poor quality of life. The predicted median age of survival for someone with CF is the early 40s. About 85% of deaths in the CF population are a result of respiratory failure.

Until recently, CF treatments could only target infection and mucus buildup, not the underlying genetic defects. New therapies, both approved and in development, are aimed at treating the underlying genetic cause of the disease:

  • Kalydeco, approved in 2012, “corrects” a very specific subset of gene defects present in approximately 5% of CF patients
  • Lumacaftor, another novel corrector treatment, is expected to be approved this year and will be used in combination with Kalydeco to treat a genetic defect present in a broader population of CF patients—an estimated 8500 patients nationally.

Patients for whom this new class of medications is effective realize additional improvements in lung function and weight gain above standard therapy. These drugs are not curative, however, and patients must maintain a complete CF treatment regimen. The new drugs are estimated to cost more than $300,000 a year—much higher than the cost of currently available inhaled therapies, which range from approximately $36,000 to $45,000 per year.

Effective management of CF requires an extensive regimen of specialty and nonspecialty therapies to treat the systemic manifestations of CF, including 2 to 4 nebulized therapies and several oral medications. Treatment commonly includes:

  • Respiratory therapy with vest/percussion techniques
  • Nutrition therapy
  • Pancreatic enzyme supplements for pancreatic insufficiency, taken several times a day in capsule form
  • Fat-soluble vitamins
  • Drugs to loosen mucus, taken once or twice daily through a nebulizer
  • Antibiotics, including oral, injected, infused, or inhaled drugs to prevent and treat acute and chronic infections
  • High-dose ibuprofen for those 6 to 17 years of age with a mild to moderate decline in lung function
  • Gene-correcting therapy

Accredo’s trained clinicians can support the complex needs of CF patients. The specialist pharmacist in the Accredo Therapeutic Resource Center reviews patient medication history upon receiving a new prescription to ensure there is no potential for adverse drug interactions and that the therapy follows clinical evidence-based guidelines. For gene-correcting therapies, we screen for the appropriate defect. Pharmacists also coordinate with physician offices, when needed, to recommend dosing regimens. This ensures patient safety and reduces waste for payers by preventing unnecessary drug costs. It can also help prevent potential downstream costs of hospitalizations and unnecessary lab tests or doctor’s visits.

Adherence is often a problem among CF patients because of a perceived lack of health benefit from the therapy or because the regimen seems burdensome. Since treatments are geared toward preserving lung function, patients may not notice a difference in how treatments make them feel on a daily basis. Inhaled or nebulized therapies can take up to 15 minutes each to administer, and a patient may have several nebulized treatments per day, with additional time for equipment set up and cleaning. Side effects—such as fatigue and simple forgetfulness—also play a role in nonadherence in an active and young CF population. Pharmacists can help patients coordinate therapy timing and dosing cycles to better fit in a patient’s lifestyle, minimizing “treatment fatigue.” Accredo also offers proactive nursing intervention and disease state education to reduce these and other barriers to adherence in the CF population.

Proper inhalation technique is vital to maximizing the amount of drug delivered to the lungs for nebulized and inhaled therapies. Nurses educate patients about proper drug administration, techniques for adherence, and managment of side effects, and help coordinate multiple therapy regimens.

With newer drugs and treatment regimens, the past decade has seen an increase in life expectancy in the CF population of almost 10 years. As more targeted mutation-specific therapies are approved and available for the wider CF population, we can expect to see additional increases in life expectancy and quality of life.

Hereditary Angioedema

HAE is a rare, debilitating condition affecting approximately 6500 people in the United States. HAE patients experience random and unchecked swelling of soft tissues with acute attacks occurring at any time. The soft tissues of the extremities, mouth/throat, abdomen, or genitals are commonly affec-ted. The swelling is often accompanied by significant pain and disability. Without treatment, attacks can last up to 5 days. They are frequently debilitating, rendering patients unable to perform normal daily activities for as many as 20 to 100-plus days each year.

HAE patients either lack or have a deficiency of a key protein—C1 esterase inhibitor—which can shut off a chain reaction leading to the production of a peptide called bradykinin, which increases vascular permeability and causes the swelling. Attacks vary in frequency and are triggered by a variety of factors including acute illness, anxiety, minor trauma, physical activity, stress, and surgery, as well as the monthly menstrual cycle or pregnancy in women.

A new C1 esterase inhibitor (recombinant) was approved in July 2014 to treat adult and adolescent patients with HAE, the fifth specialty drug to treat this orphan condition. This is the third C1 esterase inhibitor to be approved since 2008, and the first manufactured through recombinant technology. C1 esterase inhibitor protein is used both as prophylaxis, to prevent acute attacks, and as an abortive therapy.

Prior to the approval of these drugs, there were no specific treatments for this orphan disorder. Patients were treated with supportive care—typically pain management, intravenous (IV) hydration, and ventilator support for swelling in the throat—to manage acute attacks of swelling. Prophylaxis with steroids that can help to increase production of C1 esterase inhibitor was used with only marginal success due to limited efficacy in some patients and serious side effects. The new drugs have made significant improvements in quality of life for HAE patients. However, they come with a high price tag, and the regimens are complicated and can often have significant side effects.

HAE patients need a high level of coordinated care and clinical support. One rare, but serious, side effect of medications used to treat HAE is anaphylaxis, which is difficult to differentiate from a worsening attack of HAE. A trained clinician is necessary to educate the patient on recognizing the difference. Patients who present at the hospital with an attack also need to receive abortive therapy within a very short period. Untreated attacks can lead to permanent disability or tissue damage depending upon where they occur. The most severe attacks are those of the throat, which can cut off the airway and potentially cause death. Untreated laryngeal attacks can lead to the need for ventilator support.

Accredo’s extensive network of pharmacies nationwide can dispense medication/supplies to the majority of patients in the continental United States in 4 hours or less. Because HAE symptoms can be life-threatening, this is critical to supporting appropriate care. Accredo pharmacists also ensure that the patient has medication on hand in case of a scheduled event known to trigger an acute attack.

Other Accredo services for HAE patients include:

  • Access to round-the-clock clinical services, including nursing staff who can immediately access a patient’s electronic records to answer questions, triage emergencies, dispatch a skilled nurse to the home, and engage the pharmacist as needed
  • In-home visits by nurses to administer medications during an acute attack and/or train the patient on self-administration
  • Pharmacists and nurses who can coordinate with physicians to recommend treatment changes based on published evidence. Undertreatment of HAE can lead to breakthrough attacks due to inadequate response to therapy. Overtreatment can lead to waste and increased specialty spend for payers without providing any benefit to the patient.

Orphan therapies have changed the way this disease is managed, allowing patients to treat some attacks in the comfort of their home, avoiding costly visits to the emergency department. Early treatment of acute attacks helps to prevent long-term disability and provides a greatly improved quality of life for patients with HAE.


More than 1000 targeted cancer treatments are under development. Many, including new immunotherapies, are genetically guided. These new drugs target checkpoints to unmask the cancer cell so that the patient’s own immune system can destroy it. These therapies have the potential to improve outcomes for a number of cancer types when used in combination with traditional therapies.

There are several anti-programmed cell death 1 (PD-1) therapies seeking approval for the treatment of conditions including non-small cell lung cancer (NSCLC), advanced renal cell cancer, and head and neck cancers.

Therapies in this class are being approved as second-line or third-line treatments for small patient populations. In September 2014, Keytruda was the first anti-PD-1 therapy approved in the United States as a second-line therapy for advanced melanoma. Approval is being sought for its use as second-line treatment in NSCLC and breast cancer. Opdivo was the second anti-PD-1 treatment approved in the United States in 2014. It is used to treat patients with advanced melanoma previously treated with Yervoy, and approval is being sought for its use as a third-line treatment for NSCLC in mid-2015.

These therapies cost nearly $150,000 per year per patient. As IV infusions, they must be administered in a health care setting such as a hospital or infusion center.

Side effects of these immunotherapies may include colitis, hepatitis, and nephritis. Patients are often on complicated multidrug regimens, including corticosteroids, to help mitigate the side effects from cancer treatment. Extensive patient education and counseling on potential side effects, drug interactions, and symptom management are necessary. Often, the patients require close monitoring to prevent complications and encourage adherence, which is critical to success.

The specialized pharmacists in Accredo’s Oncology Therapeutic Resource Center provide patient prescription review, therapy adherence, and side-effect management support to help ensure that patients are on appropriate therapy and are tolerating their treatment, thereby increasing adherence. Through TherapEase, Accredo offers nutrition counseling programs for cancer patients during and after treatment to maintain overall health and proper nutrition.

As with all specialty therapies, effective oncology management requires the application of several different strategies. Accredo also offers a range of trend and utilization management tools to reduce waste for payers in the oncology arena. While these are applicable to orphan and nonorphan drugs, they are especially important as more high-cost drugs targeted at disease states with small, high-need populations become available.

Some strategies include:

  • Utilization management: Prior authorization (PA), drug quantity management, and step therapy are key tools in utilization management to ensure the safe and appropriate use of specialty drugs. PA policies can be applied in real time to ensure utilization conforms to appropriate standards of use. PA policies may also require genetic testing, which is especially important as more drugs come to market for specific mutations or biomarkers.
  • Exclusive specialty/channel management: Requiring that patients with complex, chronic conditions use a specialty pharmacy like Accredo can ensure that they receive care from specialized pharmacists and care teams. Benefits of a specialty requirement include safety, close monitoring to avoid gaps in care, and proactive education to reduce adverse health events. At Accredo, our protocols are designed to identify and screen for toxicity or treatment failure, and validate the accuracy of dosing, vial size, measurements, and lab values. In addition, plan sponsors gain greater visibility into their spending on specialty medications if they are dispensed through the pharmacy versus their own medical benefit.
  • Clinical days’ supply/oncology split fill: Days’ supply strategies may vary by drug, but can be key to eliminating waste and providing disease management support for the patient. For instance, with oncology medications that have significant side effects, patients often become nonadherent shortly after they begin taking the medications. Accredo’s Clinical Days’ Supply program assigns 30-day, 90-day, or titration schedules to various drugs. The program also offers initial shorter fills for appropriate medications in which a patient receives a 15-day supply of a drug followed by a call from a trained clinician who can help analyze the patient’s tolerance for the drug and provide input to a physician as to whether a drug or dosing change might be appropriate.
  • Medical channel management: Plan sponsors can exclude specific specialty drugs, such as oral oncology drugs, from the medical benefit, covering them exclusively within the pharmacy benefit to improve visibility and management of these drugs where appropriate.
  • Oncology decision support: Prescribers receive evidence-based treatment guidelines and protocols based on patient diagnosis and clinical data. Providers can compare cancer therapies based on outcomes, toxicities, side effects, and cost. The program coordinates medical care with case management and pharmacy services, and is available through Accredo’s online provider portal, ExpressPAth. SPT

About the Author

Mary Dorholt, PharmD, leads Express Scripts’ specialty clinical strategy and protocol development. In this role, Mary and her team of clinical experts develop clinical guidelines for patient care and physician interaction for this complex and growing area of the pharmacy and medical benefit. She is also responsible for driving organizational research on specialty medications and the Express Scripts experience. Dr. Dorholt has a 17-year history at Express Scripts and the former Medco organization. Prior to her current role, Dr. Dorholt was responsible for the provision of specialty strategic guidance to employer, government, and labor organizations. In this capacity, she was also responsible for marketplace oversight and internal and external communications related to specialty drug management. Dr. Dorholt has extensive knowledge and experience in the development and implementation of specialty solutions, Medicare Part D strategies, and clinical support services. She has been a frequent speaker on specialty and Medicare topics during her tenure. Dr. Dorholt received her Doctor of Pharmacy degree from the University of Minnesota College of Pharmacy in Minneapolis. She also holds bachelor’s degrees in mathematics and biology.

Related Videos
Practice Pearl #1 Active Surveillance vs Treatment in Patients with NETs
© 2024 MJH Life Sciences

All rights reserved.