What the new health care reform bill means for biosimilars and how this legislation impacts specialty pharmaceuticals.

	The Patient Protection and Affordable Care Act (PPACA) was signed into law on March 23, 2010, and contains a number of controversial provisions. One of those controversial but very significant provisions is the establishment of a biosimilars pathway, which is outlined within a mere 34 pages of the nearly 2000-page bill.

	Many of us within specialty pharmacy have followed this legislation closely and with great anticipation. Patients, physicians, and payers are looking to understand the legislation, the potential impact, and whether it will truly mean a cost savings for the health care system. Headlines related to the high cost of drugs—and specifically to the high cost of specialty drugs&mdash;appear almost daily, all of which has served to further heighten the interest and anticipation. Although the bill leaves a lot of work yet to be done by the FDA, key elements outlined include timing, exclusivity periods, pricing, and interchangeability.

	A phase-in period was not provided and the FDA may issue a guidance document; however, it is not a prerequisite for approval. It is under this premise that the FDA has signaled an “open for business” approach, where they are accepting and considering applications on a case-by-case basis. The FDA is required to begin a process to develop appropriate user fees and develop performance and safety goals for biosimilars, and to implement that process by October 1, 2012.

	Sponsors must submit their applications for biosimilars against a single reference drug that is approved in the United States. This provided the definitive answer to those who speculated that all approved European biosimilar agents would be eligible for immediate approval. New approvals will be based upon analytical studies, animal studies, and clinical studies (including immunogenicity).

	Other criteria require the biosimilars applicant to demonstrate the same mechanism of action, conditions of use, route of administration, dosage form, and strength. The approval will be for the same indications as the reference product. The bill places the burden on the FDA for evaluation and approval according to these criteria, but it also extends their authority to waive any of these criteria on a case-by-case basis.

	One of the most highly debated provisions of the biosimilars legislation was that related to the establishment of exclusivity periods. The bill allows for a 12-year data exclusivity period, which has been viewed as a win for biopharma. President Obama sought a period roughly half of that and the Federal Trade Commission went as far as to suggest that no data exclusivity period was necessary.

	The bill limits the sponsor’s ability to gain extensions based on minor changes such as route of administration, dosage form, and strength. One year of market exclusivity is granted to the first agent designated as interchangeable for any given reference product.

	Biosimilar versions of drugs reimbursed according to average selling price (ASP) received a strong endorsement in the form of pricing guidance. The construction of the bill appears to have recognized the incongruity of encouraging use of lower cost agents while basing physi-cian reimbursement on an ASP plus percentage basis. The bill provides a means for buy-and-bill drugs to be reimbursed by the sum of the biosimilar’s ASP (presumably much lower) plus 6% of the ASP amount for the reference drug. This effectively removed what would otherwise have been a disincentive to use lower cost drugs. Many of these drugs are infused, complex agents, such as monoclonal antibodies, and offer the potential for huge savings, but may take longer to gain approval. This type of pricing incentive may be very necessary and appropriate to foster competition.

	Perhaps the most significant provision within the PPACA is the establishment of an Interchangeable Biologic designation. As the bill defines it, inter-changeable biologics “may be substituted for reference product without the intervention of the health care provider who prescribed the reference product.” The criteria for establishing an interchangeable agent is not defined beyond indicating that the product should be “expected to produce the same clinical result in any given patient” and that products administered more than once should not carry increased risk of safety or diminished efficacy because of alternation or switching. It is believed that relatively robust clinical studies, particularly those which address immunogenicity concerns, will be required in order to gain the interchangeable designation.

	A primary purpose of establishing this pathway was to foster competition in order to reduce overall health care spending. Successful approval of interchangeable biosimilar agents is key to creating broad utilization of biosimilar agents. Without this designation, the biosimilar agent may need to be written for specifically, just as any other brand. Since most of the branded reference drugs have active sales forces, this creates the need for the biosimilar manufacturer to field a sales or clinical education force to educate the physician community and encourage familiarity with writing for these agents. This increases the cost and burden for the biosimilars manufacturer that may, in turn, reduce the savings that might otherwise be realized in the marketplace.

	Experience with noninterchangeable biosimilar agents in Europe suggests that these field educators are necessary to effectively compete with entrenched branded reference products. In order to maximize competition and savings potential for our health care system, interchangeability must be fostered.

	Without question, the primary consideration for all must be patient safety. Large molecules are known to be more difficult to characterize; however, that does not mean that safe and interchangeable biosimilars should be considered beyond our grasp. Effective study design and creative application of current technology can afford the means to ensure that safe and effective compounds are made available. Advance planning, well-defined study end points, and good communication will be essential to manufacturers who seek to gain the interchangeable designation.

	Since biologics have the designation of “interchangeable” versus the small molecule designation of “substitutable,” it may also leave open the door for the FDA to designate certain drugs as interchangeable only for patients new to therapy. Conceivably, this could be a solution to reduce concerns about immunogenicity as a result of alternating agents.

	As the pathway takes shape, 3 important considerations will continue to be safety, savings, and studies. The latter consideration is critical to fostering any opportunity to have the biosimilar designated as interchangeable with the reference product.

	Manufacturers will need to be diligent in planning ahead, will need clear guidance when consulting with the FDA, and should also consult their pharmacy partners to ensure that proper, meaningful research occurs. This is essential to ensuring that concerns regarding patient safety and drug efficacy are properly addressed and these new biosimilar products are made available without unnecessary delay.

	About the Author Mr. Martin is Group Vice President of Business Development at Accredo Health Group, Inc in Memphis, Tennessee. He joins Specialty Pharmacy Times as an Editorial Board member and offers his insights into the biosimilars market with this article. The Accredo Health Group, Inc is headquartered in Memphis, Tennessee and provides specialty pharmacy and related services for patients with complex and chronic conditions through its Therapeutic Resource Centers.

Articles

Features

Biosimilars: Could This Be a Pearl in the Patient Protection and Affordable Care Act?

This new journal embraces the entrepreneurial spirit of specialty pharmacy. 

 has a long history of being the leading-edge publication, designed to enhance both the business and the profession of pharmacy. The most dynamic elements in pharmacy today are specialty pharmaceuticals and the professional support necessary to assure optimal outcomes for patients who are treated with these products.

 is pleased to announce a unique stand-alone publication—

 will be focused on the many key areas surrounding specialty pharmaceuticals and the enhanced practice needs of pharmacists and other key ancillary personnel.

 content will be directed in all of the key areas necessary for its readers to stay abreast of the practice of specialty pharmacy. Future articles will focus on the actions practitioners must undertake to succeed in this business, including product selection, infrastructure, staffing, pharmacy design, reimbursement, customer service and order management, and marketing and sales, and will also include several clinical programs. To maximize their opportunities, pharmacists and other ancillary professionals must become proactive—and seize the moment&mdash; to find new methods to thrive in this dynamic marketplace.

	We also recognize that the payer community (ie, managed care organizations and employers), specialty pharmaceuticals manufacturers, government, allied health care professionals, and community pharmacy all play a key role in the future, and therefore our content will include these key topics. 

 will provide insights from the leaders of specialty pharmacy practice and experts in policy, regulatory and law, academia, information systems, and business. Our writers will come from all areas of practice, including administration, law, management, nursing, and importantly, from pharmacists who interact with patients on a daily basis.

	The history of specialty pharmacy began with a grass roots effort of community pharmacy, recognizing that many patients with emerging therapies had unique therapy needs. That entrepreneurial spirit has continued to thrive and specialty practice has grown exponentially.

	We will provide new concepts and deliverables to assist those professionals who are interested in expanding their practice within the specialty pharmacy segment. 

 will embrace that entrepreneurial spirit and provide its readers with a unique new platform to take their knowledge to the next level. We thank you for your interest and look forward to your feedback as we strive to set new standards in professional practice.

About the Editor-in-Chief, Specialty Pharmacy Times

Dan Steiber, RPh, is a Principal of D2 Pharma Consulting LLC (www. d2rx.com) and is responsible for commercial operations, tradesupply chain strategy development including 3PL selection, regulatory oversight, and “operationalizing” organizations. Dan has served in several senior positions in pharmacy, distribution, and industry over the course of his 35-year career. He is a licensed pharmacist in California, Pennsylvania, Texas, and Washington. He is also affiliated with several professional associations and publications and is a frequent speaker on behalf of many professional organizations. He graduated from Washington State University College of Pharmacy and participated in a variety of postgraduate programs in law and business development/ marketing at Harvard University and Northwestern University. Dan currently resides in Plano, Texas, with his wife and 2 sons.

Editorial

Introducing Specialty Pharmacy Times:  Seizing the Moment

What each stakeholder needs to know about REMS in today's fast-paced climate. 

Three years ago, Congress passed the FDA Amendments Act, which empowered the FDA to require Risk Evaluation and Mitigation Strategies (REMS) for new and existing products. The number of REMS required for products has steadily grown since the first programs were introduced in 2008. 

	Nearly 90% of these REMS have required a health professional communication plan and patient medication guide. For products with more serious safety concerns, the FDA requires pharmaceutical manufacturers to administer REMS with Elements to Assure Safe Use (ETASUs). These elements require manufacturers to institute post-market safety prescriber or patient registries, controlled distribution, and other tools.

	While all REMS have the potential to improve safety, programs with ETASUs are most likely to have unintended consequences on health care stakeholders, including reduced access or increased burden. In the specialty market segment, REMS with ETASU have the highest prevalence compared with the rest of the market.

REMS’ Impact on Stakeholders Increasing

	With more medication guides, communication plans, and REMS with ETASU, stakeholders—including physicians, pharmacists, specialty pharmacies, and distributors&mdash;have all had to alter their work flow and engage in activities supporting REMS on patients’ behalf. As the number of these programs increases, the need to indentify strategies for REMS’ success that enable patient access and minimize unnecessary disruption to business and clinical practice is intensified. The FDA explicitly states that it seeks to avoid what they term “unintended consequences” of REMS programs, including reduced access and increased burden to the health care system.

	Nevertheless, the FDA can only advise on submitted REMS programs and is not directly involved in the program design details. The biotech and pharmaceutical company sponsors must design and prepare for the execution of their REMS, while hopefully minimizing the impact on stakeholders. Also, the FDA does not usually have any direct regulatory interaction over many of the stakeholders of REMS (eg, pharmacies) that are directly affected by REMS programs. REMS require many stakeholders to work together to increase the safe use of products and reduce the potential for adverse events.

	The patient can have a variety of responsibilities, depending on the extent of the ETASU. At minimum, a patient medication guide is typically presented to the patient for review. Also, under ETASU, patients can be required to undergo training, testing or complete follow-up clinical counseling calls while on therapy.

Physicians and Other Health Care Providers

	Physicians and other health care providers have a responsibility to understand the REMS requirements and engage with their patients to comply with them before initiating, and while maintaining, patients on therapy. The responsibilities that a physician has for REMS can vary greatly for each product. They can be as minimal as the distribution of a medication guide when the product is administered in the office, or as involved as completing a training course and providing baseline and ongoing follow-up status to the REMS program administrator on each patient on therapy.

	Pharmacies and pharmacists also play important roles in the administration and management of REMS programs. Most REMS require that a medication guide be given to patients, and often this responsibility is on the dispensing pharmacist. In REMS with ETASU, often the design of the program calls for limiting access of the product to a more narrow set of dispensing pharmacies that will agree to comply with the REMS program requirements.

	These dispensing pharmacies may, in some of the most restrictive REMS, undergo special education and training and be required to ensure that each dispensed prescription is written by a registered prescriber and is being given to a registered patient. These more comprehensive programs are attempting to use the point of dispense as the final checkpoint to ensure that only those patients who qualify are given the product.

	Specialty distributors and wholesale distributors also may have controls that they are responsible to administer in REMS programs. As part of becoming a certified distributor of REMS with ETASUs, distributors may need to ensure that product is only distributed to locations that are enrolled and registered in the REMS program. Also, distributors may be required to provide data to pharmaceutical manufacturers to complete their required data sets, which must be delivered to the FDA to stay in compliance with the agreed requirements of their REMS.

	Most pharmaceutical manufacturers contract with a REMS Program Administrator to provide centralized regulatory- compliant services for the collection and maintenance of all data elements, which must be reported back to the FDA resulting from the agreed upon REMS. Services include designing and maintaining the registries of prescribers, pharmacies, distributors, and patients required by ETASUs.

	Often there are also call center support services to help address the questions and needs of stakeholders impacted by the REMS. These Program Administrators are also involved in the strategy, development and implementation of surveys and assessments provided to the FDA to determine if patients are receiving and understanding the content of the medication guides. Periodically, REMS Program Administrators provide data reports back to manufacturers from validated databases and deliver data sets to the pharma manufacturers, who then reports results back to the FDA.

Responsibilities of the Pharmaceutical Manufacturer

	The pharmaceutical manufacturer is responsible for designing the REMS program to meet the safety objectives for their product. They must ensure compliance with the REMS program, which means that a Program Administrator must be identified and periodic reports of data must be made to the FDA on progress against the objectives of the REMS. The manufacturer must also track and collect adverse events and report them to the FDA.

	Manufacturers must also work to ensure that access is supported for their products beyond REMS. Often this includes reimbursement patient assistance programs (PAPS), patient support services for therapy initiation, and support adherence and persistence to therapy. These services are often contracted to support services call center hubs and can be synergistic to the Program Administration services provided as part of a REMS.

	Many stakeholders must align and remain accountable to the delivery of safer product use in the market. REMS require more of each stakeholder group and can force changes in processes, work flow and data collection, and reporting. Ultimately, it requires a careful balance to limit reduction in access with mitigating risks.

Heather Morel, MBA is vice president and general manager of reimbursement & access services for McKesson Reimbursement, Access and Safety Services in Scottsdale, Arizona. Morel leads the development and execution of reimbursement strategies and support services, patient assistance programs, risk evaluation and mitigation strategies programs, and other patient and physician-focused initiatives. She is a nationally recognized expert in health care reimbursement and marketing. Ms. Morel is a member of the 

Focus on REMS

Risk Evaluation and Mitigation Strategies in the Specialty BioPharma Market

Our Washington columnist keeps you abreast as the rules of the game are changing. 

	In March of this year, the Affordable Care Act (ACA) again amended the legal definition of average manufacturer price (AMP). AMP uniquely serves to determine both a multiple source drug’s reimbursement amount and the rebate amounts for single source, innovator single source, and multiple source drugs within the Medicaid program. No other pricing metric serves this dual function. As such, Congress, and particularly Senator Max Baucus (D-MT), has over the years repeatedly attempted to change the definition of AMP for the benefit of pharmacists and to generate more money for federal and state governments.

	As many already know, when the health reform legislation passed earlier this year, the definition of AMP changed. It became the average price paid to the manufacturer for the drug in the United States by wholesalers for drugs distributed to retail community pharmacies and by retail community pharmacies that purchase drugs directly from the manufacturer. The health reform law also excludes payments and rebates or discounts provided to certain providers and payers from the calculation of AMP.

	These changes seem to accomplish the objective of raising the AMP such that pharmacists will be reimbursed more because their reimbursement rate is tied to the AMP. Score one for Senator Baucus. Additionally, in the health reform law, Congress increased the rebate percentage 8 percentage points—from 15.1% to 23.1%. The effect of this is to raise money from manufacturers for both federal and state governments. Yet another point for Senator Baucus.

	As one digested this new AMP definition, however, it became clear that many specialty products no longer fit within this definition. The majority of specialty products are not available, nor should they be available, at a retail pharmacy. This brought into question whether manufacturers needed to report an AMP for their specialty products. This clearly was not Congress’ intent. Minus one for Senator Baucus—and as we know, the chairman of the Finance Committee does not like to lose any points. This required further Congressional action. Therefore, as part of the Education Jobs and Medicaid Assistance Act that the President signed into law on August 10, 2010, Congress yet again amended the definition of AMP. The Act clarifies that effective as if included in the enactment of the ACA, an inhalation, infusion, instilled, implanted, or an injectable drug that is not generally dispensed through a retail community pharmacy is not excluded from the AMP calculation.

	In other words, specialty products are back in the definition of AMP as of the day that ACA became law. Problem solved and game over with all the points to the Senator. Isn’t that special?

	With specialty products back in the AMP calculation, the foundation for the new Medicaid market for specialty products has been established. In addition to changing the definition of AMP, ACA now requires Medicaid rebates on all therapies accessed through a managed care organization. Previously, if a Medicaid recipient accessed a therapy through a managed care organization, the manufacturer was not obligated to pay a rebate on that utilization. This created a disjointed marketplace as some states carved out the pharmacy benefit in their managed care contracts to keep rebate dollars. The need to do this no longer exists.

	States will get to keep some of the rebate dollars regardless of whether the Medicaid recipient accesses the therapy through a Medicaid managed care organization or not. As a result, many more states will probably contract with managed care for the entire Medicaid benefit package, which will include the pharmacy benefit and specialty products. Therefore, manufacturers must monitor state contracting activities and reexamine contracting strategy as this new market evolves. The games rules are changing for manufacturers who, unlike Congress, do not get the chance to turn back the clock.

Mr. Slotnick focuses on health care regulatory issues in his current practice at Foley Hoag LLP. Jayson was formerly the Director of Medicare Reimbursement and Economic Policy at the Biotechnology Industry Organization in Washington, DC, where he represented the industry in front of the Centers for Medicaid & Medicare Services, the US Congress, and other regulatory agencies. He joins 

 as the regular columnist of “Washington Insights” and an Editorial Board member.

Washington Insights

 The Special Definition of Average Manufacturer Price

"An optimist sees the opportunity in every difficulty." 

	This famous quote comes to mind when thinking about the current state of the specialty pharmacy industry. There is no doubt that society is reaping enormous benefits from the advancements in specialty pharmaceuticals that are improving treatment outcomes for many serious conditions such as multiple sclerosis, hepatitis C, cancer, and others.

	At the same time, the specialty trend— the percentage increase in medication cost year-over-year&mdash;is growing at triple the pace of the overall pharmaceutical market. Not surprisingly, some are questioning how long the system can support this cost trend given the current health care environment and the huge pipeline of specialty medications under development.

	The challenge becomes even more relevant to the specialty industry as we’re asked—and sometimes told&mdash; that we bear responsibility to Ensure Appropriate Use, Optimize Safety and Efficacy, and Preserve Affordability for the use of these innovative products.

	While this is not a new challenge, the growth in the specialty trend, expensive drug costs, and the sheer number of new specialty products on the horizon, means that we must rely on methods that have worked in the past, even while we develop new and innovative approaches that will help patients and payers balance product benefit versus incurred cost. Some of the approaches highlighted below will be expanded for future topics—and focus areas of this new specialty pharmacy periodical.

	Studies by the Institute of Medicine, RAND, and other organizations have highlighted the gap between scientifically based approaches to care and day-to-day practice by clinicians. Evidence-based guidelines are often developed to address this gap and represent the ongoing systematic review of the “science” around the diagnosis and treatment of specific conditions. These guidelines can be an effective tool in ensuring the appropriate, safe, and cost-effective use of specialty products. Specialty pharmacy is playing an expanded role in validating that specialty pharmaceuticals are being used within such guidelines.

Personalized Medicine and Pharmacogenomic Testing 

	This is the fastest growing and most exciting segment of our clinical arsenal for the use of specialty and other pharmaceutical products. Today, we have a handful of readily available pharmacogenomic tests that correlate an individual’s genetic makeup to how he or she may respond to a specific drug. For example, HER2 testing predicts the likely clinical response to Herceptin for breast cancer, and CYP2C9 measures an individual’s specific metabolism rate for certain drugs, such as warfarin, and assists with optimal dosing prior to writing the first prescription.

	As the science presents us with more of these advanced tests, clinicians will be able to personally tailor pharmaceutical interventions while increasing the likelihood of a safe and positive clinical outcome.

Risk Evaluation and Mitigation Strategy (REMS) 

	REMS programs date back to the launch of Clozaril in the early 1990s, when the FDA required monitoring for agranulocytosis prior to dispensing another refill of the drug. Since then, the FDA has increasingly relied on REMS as a method to mitigate the risks and known adverse effects of an approved drug. A significant and important responsibility has been placed on the dispensing pharmacy and the pharmacist to ensure the proper administration of these critical safety programs. The number of REMS programs will substantially increase in the future and our roles as pharmacists and specialty pharmacies will be put to critical use.

	Since the passing of the Hatch-Waxman Act in 1984, generics have provided an effective clinical alternative that yields substantial cost savings to patients and payers. The opportunity exists to replicate this dynamic with biologics, although with a heightened level of complexity that should not be overlooked. As biologics have a very complex manufacturing process that differs greatly from that of small molecules, there is ongoing debate over the criteria to demonstrate bioequivalence.

	However, the recent passage of the Affordable Care Act (ACA) brings us one step closer to establishing this groundwork by creating a formal legislative pathway for approvals of biosimilars by the FDA. Even with this pathway in place, it is likely that many biosimilars will not be interchangeable and will require that a pharmacist receive a new prescription. Our role in helping patients and payers obtain the desired outcomes at the lowest cost will remain a top priority as we are asked to assist in driving adoption of these future therapeutic alternatives.

Specialty Formularies and Preferred Drugs 

	As therapeutic areas have become more crowded with specialty drugs, payers are increasingly able to evaluate products in a category and select a preferred product that yields the desired outcome at the lowest possible cost. This opportunity has led many managed care organizations to require the use of their preferred formulary product in order to obtain coverage. As this becomes even more prevalent, pharmacies will be increasingly responsible for intervening when the prescription is not written for the preferred alternative. We must maintain focus on our role within pharmacy of assisting patients and payers in managing the costs associated with drug therapy.

	In the end, specialty pharmacy is at the center of some of the most exciting developments in health care. As pharmacists within the specialty pharmacy segment, we have established ourselves as a trusted source for delivering an increasingly complex level and quality of care. But our work has just begun, and just as with any segment of any industry, we must keep a keen eye on future needs and requirements to advance our value even further. While it will not be easy…I am an optimist.

Mr. Golding is the Executive Vice President of Specialty Pharmacy Services at CVS Caremark.

Viewpoints: The Last Word

Optimism and Opportunity

	Several new specialty medications are expected to be approved in the remainder of 2010. New, infused therapies to treat gout and lupus may enter the market. The FDA just approved the first oral, disease-modifying drug for multiple sclerosis and should soon approve the second. In addition, the first medication approved to treat HIV-related lipodystrophy is expected to gain FDA approval. More information about these specialty medications follow.

	Krystexxa (pegloticase) is a recombinant, pegylated formulation of porcine uricase (urate oxidase) that lowers levels of uric acid in the blood. Krystexxa was approved by the FDA on September 14, 2010. It is administered every 2 weeks as an intravenous (IV) infusion. Krystexxa is approved for the treatment of chronic gout in patients who are refractory to conventional therapy such as xanthine oxidase inhibitors (eg allopurinol). There are about 100,000 patients in the United States who will be candidates for treatment with Krystexxa.

	It’s estimated that Krystexxa will cost $50,000 per patient for one year of therapy. It was approved with a Risk Evaluation and Mitigation Strategy (REMS) that notifies patients and prescribers about the risks of severe infusion reactions and possible anaphylaxis.

	Benlysta (belimumab) may be the first medication approved to treat lupus in more than 50 years. It is a fully human monoclonal antibody that inhibits the biologic activity of B-lymphocyte stimulator (BLyS), a protein required for the development of B lymphocytes into mature plasma B cells. Elevated levels of BLyS are thought to contribute to the production of autoantibodies. After an induction phase, Benlysta is administered as a monthly IV infusion. It is in development to treat patients with systemic lupus erythematosus (SLE). Approximately 100,000 patients in the United States will be candidates for treatment with Benlysta. It is expected to cost between $25,000 and $50,000 per year. The FDA will likely approve Benlysta by December 10, 2010. The medication is also in earlyphase development for the treatment of rheumatoid arthritis.

	Gilenya (fingolimod) and Movectro (cladribine) are oral, disease-modifying drugs for the treatment of multiple sclerosis (MS). Gilenya was approved by the FDA September 22, 2010; Movectro is still in development. While the mechanisms for these medications differ, they are both very effective in reducing relapse rates in patients with relapsing remitting MS (54% to 60%). However, both Gilenya and Movectro do carry risks. Gilenya use has been associated with significant drops in heart rate, macular edema, and evaluations in liver enzymes. Movectro may suppress white blood cells, thereby increasing the the risk of serious infections. Gilenya was approved with a REMS program to inform patients and health care professionals about the risks of using it in the treatment of relapsing forms of MS. Movectro will also likely be approved with a REMS program due to its safety profile.

	Gilenya will cost cost as much as $48,000 annually. The FDA is expected to approve Movectro by December 8, 2010. It is possible that these medications will be used in the first-line setting before the injectable biologic medications that are currently on the market to treat MS.

	Egrifta (tesamorelin) is a growth hormone-releasing hormone (GHRH) receptor agonist in development for the treatment of HIV-related lipodystrophy. It works by reducing visceral fat tissue without reducing subcutaneous fat tissue. It is administered once daily by subcutaneous injection. Lipodystrophy, or abnormal fat accumulation, can be a side effect of HIV protease inhibitors. The HIV virus itself may also contribute to a patient’s lipodystrophy. Currently, there are no FDA-approved medications for this condition.

	It is estimated that anywhere from 200,000 to 800,000 patients in the United States have HIV-related lipodystrophy. In June 2010, an FDA advisory panel voted unanimously in favor of the approval of Egrifta. The FDA is expected to approve this medication in late October.

Dr. Tharaldson is Senior Clinical Consultant, Emerging Therapeutics, at Express Scripts.

New Product Pipeline

Near-Term Specialty Pipeline Highlights October 2010

	Privigen, Immune Globulin Intravenous (Human), is available as a 10% liquid preparation of polyvalent human immunoglobulin. Indications include the treatment of primary humoral immunodeficiency (PI) associated with defects in humoral immunity, including but not limited to common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA), congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

	Privigen is also indicated to rapidly raise platelet counts to prevent bleeding in patients with chronic immune thrombocytopenic purpura (ITP).

 Mechanism of Action Privigen is an antibody replacement therapy for PI, and supplies a broad spectrum of opsonic and neutralizing immunoglobulin G antibodies against bacterial, viral, parasitic, and mycoplasma agents and their toxins.

The specific mechanism of action in the treatment of PI or the use of high doses of immunoglobulins in the treatment of chronic ITP has not been fully elucidated, however.

	Privigen has been studied in patients with both PI and chronic ITP.

 The efficacy, safety, and pharmacokinetics of Privigen in patients with PI was investigated in a prospective, open-label, single-arm, multicenter, phase III study.

 The study was performed involving 80 subjects with XLA or CVID who had been receiving intravenous immunoglobulin (IVIG) replacement therapy for at least 6 months prior to study entry.

Patients received Privigen at individually adjusted doses ranging from 200 to 888 mg/kg for 12 months.

 Efficacy was determined by the rate of acute serious bacterial infections (aSBIs). The annual aSBI rate during the 12-month study period was 0.08 per subject, and met the predefined success rate of less than one aSBI per patient per year.

	A prospective, open-label, single-arm, multicenter study evaluated the efficacy of Privigen in 57 subjects with chronic ITP and a baseline platelet count of 20 x 109/L or less.

 Subjects received a cumulative 2-g/ kg dose of Privigen, administered as two 1-g/kg intravenous infusions for 2 consecutive days and were observed for 29 days.

The primary end point was the response rate, defined as the percentage of subjects with an increase in platelet counts to at least 50 x 109/L within 7 days after the first infusion.

 Of the 57 subjects in the efficacy analysis, 46 (80.7%) responded to Privigen. Median time to response was 2.5 days.

	Safety and efficacy of Privigen have not been evaluated in nursing mothers. Privigen is listed as pregnancy category C.

 Privigen should be given to pregnant women only if clearly needed. The safety and effectiveness of Privigen has not been established in pediatric subjects with PI who are under the age of 3 years

or in pediatric subjects with chronic ITP who are under the age of 15 years.

	Privigen is available as a solution in the following strengths: 5 g in 50 mL solution, 10 g in 100 mL solution, and 20 g in 200 mL solution, and is intended for intravenous administration only.

	Recommended dosing for PI is 200 to 800 mg/kg intravenously (IV) every 3 to 4 weeks. The recommended initial infusion rate is 0.5 mg/kg/min (0.005 mL/kg/min) and, if well-tolerated, may be gradually increased to a maximum of 8 mg/kg/min (0.08 mL/kg/min.)

 Dosing for ITP is 1 g/kg IV daily for 2 consecutive days, for a total of 2 g/kg. Recommended initial infusion rate is 0.5 mg/kg/min (0.005 mL/kg/min) and, if well tolerated, may be gradually increased to 4 mg/kg/min (0.04 mL/kg/min). In patients at risk of developing renal insufficiency, do not exceed the recommended dose, and infuse Privigen at a rate less than 2 mg/kg/min (0.02 mL/kg/min).

 Privigen does not contain sucrose and is stabilized with the amino acid proline, which allows Privigen to remain stable for 36 months at room temperature.

	In clinical studies, the most common adverse reactions reported among patients receiving treatment for PI were headache (44%), pain (25%), nausea (13%), fatigue (16%), and chills (11%).

 Common adverse effects associated with treatment for ITP include headache (65%), pyrexia/hyperthermia (37%), and anemia (11%).

 Renal function should be monitored, including blood urea nitrogen, serum creatinine, and urine output, in patients at risk of developing acute renal failure.

 Patients should be monitored for hyperproteinemia, hyponatremia, hemolysis/transfusionrelated acute lung injury, hemolytic anemia, and pulmonary adverse reactions. Patients should also be monitored for thrombotic events, especially those patients with risk factors for thrombosis, including those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity.

 Caution should also be used because aseptic meningitis syndrome (AMS) may occur infrequently with Privigen and other IVIG treatments.

 AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of immune globulin intravenous products.

	Privigen is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin, in patients with hyperprolinemia, and in immunoglobulin A (IgA)-deficient patients with antibodies to IgA and a history of hypersensitivity.

	1.  Privigen Prescribing Information. CLS Behring Web site. Available at: www.privigen.com/pdf/Privigen_PI.pdf. Accessed September 27, 2010.

	2. Privigen IV Monograph. Medscape Web site. Available at: www.medscape.com/druginfo/monograph?cid=med&drugid=149963&drugname=Privigen+IV&monotype=monograph&print=1#Pharmacology. Accessed September 27, 2010.

	3. Privigen (human immunoglobulin g) liquid. National Institutes of Health Daily Med Web site. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=17108#nlm34090-1. Accessed September 27, 2010.

	4. Stein MR, Nelson RP, Church JA, et al. IgPro10 in PID Study Group. Safety and efficacy of Privigen, a novel 10% liquid immunoglobulin preparation for intravenous use, in patients with primary immunodeficiencies. J Clin Immunol. 2009; 29(1):137-144.

	5. Efficacy and Safety in Patients with Primary Immunodeficiency Disease (PIDD). CLS Behring Web site. Available at: www.privigen.com/Professional/Efficacy-Safety/Primary-Immunodeficiency.aspx. Accessed September 27, 2010.

	6. Efficacy and Safety in Patients with Immune Thrombocytopenic Purpura (ITP). CLS Behring Web site. Available at: www.privigen.com/Professional/Efficacy-Safety/Immune-Thrombocytopenic.aspx. Accessed September 27, 2010.

	7. Important Safety Information Regarding Privigen. CLS Behring Web site. Available at: www.privigen.com/Professional/default.aspx. Accessed September 27, 2010.

Ms. Terrie is a clinical pharmacy writer based in Haymarket, Virginia.

New Drug Review

CSL Behring's Privigen

The personal story of a specialty pharmacist and the growth of an industry. 

If you ask the question “What is specialty pharmacy?” you will receive many different responses.

	For payers, like the Centers for Medicare & Medicaid Services, the answer may involve cost. For manufacturers, it may involve benefit analysis and reimbursement assistance. But for me, “specialty pharmacy” means patient care.

	As a pharmacist and owner of an independent specialty pharmacy, one of the most rewarding aspects of my work is improving our patients’ quality of life. I think all of the stakeholders would agree that “specialty pharmacy” involves a hi-tech, hi-touch approach to effectively manage patients with chronic conditions requiring expensive medications that may need special handling, and also requiring additional patient support to keep patients compliant—and ultimately improve patient outcomes.

	Building a practice that goes beyond the traditional count, pour, lick, and stick mentality is a tremendous endeavor. It requires a great deal of infrastructure, knowledge, and capital. The cards are stacked against you with limiteddistribution pharmaceutical agreements, PBM-owned specialty pharmacies limiting patient access, and networks that only have a select few participating specialty pharmacies.

	Our practice is built around “improving our patients’ lives.” With this in mind, we leverage our relationships with physicians and health care professionals to offer a viable solution. We work closely with the medical offices that entrust us with these patients who require an array of different services.

	Our collaborative staff works vigorously to ensure that every new patient receives their medication, even if we are restricted because of insurance or manufacturer programs in providing the medication from our facility. We continue working with the referral, sending it to the mandated pharmacy and communicating with both the patient and provider.

	One of the most valuable and self-rewarding services we offer is injection-training and face-toface counseling for our patients and caregivers. We provide specialty patients, who require assistance, the opportunity to sit down in a private setting and learn about their condition and medication. We partner with local pharmaceutical representatives to provide starter kits and additional valuable information for our patients. We believe that communication is an important component of improving compliance, adherence, and ultimately outcomes, so we have an ongoing interaction with our patients and their physicians. Our specialty pharmacy services are integrated around the patient and their health care provider.

	I believe that community specialty pharmacies have a tremendous opportunity to make a difference for patients who require specialty medications. The process is not an easy one administratively, with just about every patient requiring a prior authorization, follow-up, and insurance verification. You need a dedicated staff with an in-depth understanding of the medications and their respective disease states.

	Specialty pharmacy is not an avenue for every community pharmacy; however, if you deliver high-quality service, physicians and patients will surely recognize that community specialty pharmacies are the most appropriate choice for their medication needs.

	When you think about it, most current providers of specialty medication are using a DVD for patient education, a nonlocal call center operator, and a UPS driver to deliver their services to their patients. Is this really the appropriate scenario for patients who require complicated care to ensure optimal outcomes?

Serving the Community, Growing Niche Services 

	Nicholas Karalis, RPh, has owned and operated 6 stores in the 20 years since he graduated from the Philadelphia College of Pharmacy and Sciences in Philadelphia, Pennsylvania. In a recent profile in RxNotes, published by Cardinal Health, his specialty pharmacy team at the Elwyn Specialty Care in Glen Mills, Pennsylvania, is pictured alongside “Nick” and his brother Jim, also a pharmacist. Obviously, the endeavor is a team effort. Founded in 2008, this specialty pharmacy and long-term care facility serves more than 5000 patients living in skilled/assisted living, intermediate care facilities, group homes, and prison systems in the community.

	Specializing in a wide range of disease states, Elwyn Specialty Care offers specialty pharmacy services in HIV, oncology, hepatitis C, multiple sclerosis, rheumatoid arthritis, Crohn’s disease, psoriasis, and other areas that require special-handling and self-injection medications. The extensive multiple sclerosis program is just one example of how this pharmacy handles patient care from start to finish—helping patients achieve the best results and optimum treatment for their condition. The process starts with reimbursement and prior authorization assistance and goes on to injection training by trained team members, and also includes refill reminders, delivery, and compliance/adherence and data outcome collecting and reporting.

Mr. Karalis is a specialty pharmacist and co-owner of Elwyn Specialty Care in Glen Mills, Pennsylvania. As an independent pharmacy owner, he has seen the field of specialty pharmacy evolve. A leading voice in community pharmacy, Karalis is a founding member and board member of the Community Specialty Pharmacy Network (CSPN), as well as a board member of the Cardinal Health National Home Health Care Advisory Board. 

welcomes him as an Editorial Board member with this first issue. 

Specialty Speaks

Life in a Specialty Pharmacy

Specialty pharmacists and related health care professionals can choose to attend a variety of meetings, conferences, and special events to enhance their professional practices and understanding of health care issues today. Here are some select upcoming meetings and conferences to consider:

74th Annual Scientific Meeting • November 7-11, 2010 • Atlanta, Georgia 

 Health care professionals can take advantage of the intimate “Meet the Professor” sessions and Workshops offered at the ACR Annual Meeting, as well as participate in guided tours of the many poster sessions. A host of clinical sessions and presentations will be presented, including the Innovative Therapies in Autoimmune Diseases Conference, which is presented every other year.

	AMERICAN SOCIETY OF CONSULTANT PHARMACISTS (ASCP)

41st ASCP Annual Meeting & Exhibition • November 10-13, 2010 • Gaylord Palms & Resort Convention Center, Orlando, Florida 

 The ASCP invites pharmacy professionals to attend this meeting to gain education and training, view hands-on, in-person demonstrations, and network with their colleagues. The meeting offers presentations on the latest trends, research, clinical practice, and products.

Scientific Sessions 2010 • November 13-17, 2010 • Chicago, Illinois 

This educational convention offers health care professionals with a wide variety of cardiovascular sessions, with tracks in Diabetes, Nursing, General Cardiology, and Interventional Cardiology among the themes. Attendees will have the opportunity to attended 16 Late-Breaking Clinical Trial reports, visit the exhibition floor, and attend clinical sessions. An e-book of the 2010 AHA Advance Program is available online to review the meeting’s sessions and events.

 www.scientificsessions.americanheart.org

	THE WORLD CONGRESS LEADERSHIP SUMMIT ON THE PATIENT CENTERED MEDICAL HOME

November 17-19, 2010 • San Diego, California 

 Health care reform promotes the Patient Centered Medical Home as the future of care delivery in the United States and as a model to achieve better outcomes and cost savings through effective coordination of care. This meeting focuses on this new trend.

	AMERICAN SOCIETY OF HEALTHSYSTEM PHARMACISTS (ASHP)

45th ASHP Midyear Clinical Meeting & Exhibition • December 5-9, 2010 • Anaheim Convention Center, Anaheim, California 

 The focus of this meeting is on improving patient care and medication safety. Attended by more than 20,000 pharmacy professionals from 86 countries, it provides health system pharmacy practitioners with a venue for updating their knowledge, networking with colleagues, enhancing their skills, and learning about the latest products and innovations. 

	THE 7TH ANNUAL AMERICAN HEALTH CARE CONGRESS (AHCC)

Integration Strategies to Address Health Care Reform Implementation Strategies • December 7-8, 2010 • Irvine, California 

This executive forum is designed to educate health care executives on integration strategies post-health care reform and offer strategies to identify operational changes needed for increased reimbursement, develop aligned incentives across the network, and leverage health care IT.

Conference Calendar

Upcoming Fall/Winter Meetings

Current trends in the marketplace dictate new approaches and analyses. 

	There’s a tsunami of specialty pharmaceuticals headed our way. It is estimated that approximately 57 million working age Americans live with diabetes, asthma, rheumatoid arthritis, cancer, HIV, and other serious diseases.

 Many of these people are able to continue working and be productive members of their communities due, in large part, to the introduction of these highly effective specialty pharmaceuticals.

	For the first time since the pharmacy industry began tracking such things, the consensus forecast is that by 2014 the top-selling drugs by revenue in the United States will move from so-called “small molecule oral solids” to larger molecule injectable specialty medications, including several new oncology products.

	For example, the consensus forecast for 2010 sales is:

	1. Lipitor (cholesterol)* $11.7 billion Pfizer

	2. Plavix (anti-clot)* $9.6 billion Sanofi/Bristol

	3. Advair (asthma/COPD) $9 billion GlaxoSmithKline

	In comparison, the top 3 pharmaceuticals in 2014 will be specialty or oncology drugs—forecasted to represent $25.4 billion in sales:

	2. Humira (arthritis) $8.5 billion Abbott

	3. Enbrel (arthritis) $8 billion Pfizer/Amgen

	While the definition of specialty continues to evolve, most classifications include nearly 400 different drugs across 25 therapeutic categories. Specialty pharmaceuticals now represent more than 25% of the total drug spend, with estimates that this will climb to more than 40% by 2030. In such an environment, where the pipeline is filling up with specialty drugs, it will be even more challenging to ensure that payers, employers, and their members receive affordable, clinically sound treatment options.

	Adding the 12-year exclusivity for biologics in the new Patient Protection and Affordable Care Act only heightens the importance of thoughtfully addressing the delivery and clinical management components for these often highly effective, yet most expensive prescription medications.

	The cost of a biologic agent for just one patient averages between $1000 and $1500 per month,

 with certain treatments vastly exceeding these averages. Despite the cost challenges, the substantial demand by patients and the push for new discoveries by drug companies will drive increasing utilization of these treatments. Thus, employers’ health plans and government stakeholders must explore new methods to control the cost/benefit equation of these drugs and therapeutic regimens. While costly, their value must not be underestimated. Specialty drugs can improve clinical outcomes, productivity, and quality of life for millions of patients with chronic illnesses.

Meaningful Total Health Outcome Analytics 

	While cost-effective treatments and regimens have always been the stated goal of any payer or health care provider, these new drugs bring increasing attention to the overriding desire to control health care costs while providing optimal outcomes, particularly in the post—health reform era. It is currently the payers and most recently the FDA— through Risk Evaluation and Mitigation Strategies (REMS) controls over pharmaceutical manufacturers&mdash;that are driving the requirements of products and services included in the specialty pharmacy sector.

	These distinct stakeholders are the catalysts for new and enhanced specialty pharmacy services. Such services are employed to maximize the value of medications to patients who need them, with an eye toward meaningful total health outcome analytics not widely or sufficiently available today.

	While exceptions do exist across the pharmacy industry, payers are increasingly viewing most traditional pharmaceutical delivery systems as being challenged by the rapidly shifting dynamics associated with specialty pharmaceuticals. Payers will continue to establish requirements and influence business models that can achieve the total health outcomes and costs controls that must be achieved. To date, selected models have included open and limited networks, partnerships, management agreements, payer in-sourcing, and variations of these.

	One size may not fit all, and the best-fit model will depend on a complex set of factors, including a fair amount of trial and error over time. However, the current trend is for payers to move away from the traditional community pharmacy networks in search of systems that can better achieve the overarching goals. Likewise, pharmaceutical manufacturers driven by REMS requirements and the need to have better controls over their products and related services are narrowing their contacting networks.

	With these forces coming to bear, what are some of the differentiated aspects of a sophisticated specialty pharmacy that will drive the business models of tomorrow?

	As a baseline, traditional, efficient delivery systems with high-quality service to consumers and payers at competitive prices are and will be mere “table stakes” when competing in the specialty sector.

	• “High touch” proactive care management systems; sophisticated data collection, reporting and analytics; and effective and evidence-based adherence and persistency programs along with protocol driven clinical management programs, to name but a few.

	• The ability to address and solve for the differences in pharmacy versus medical drug benefits relative to provider networks, reimbursement, and regulatory requirements.

	• Participation in REMS programs and associated pharmaceutical company service agreements.

	These and other aspects of specialty pharmaceuticals have resulted in new business and pharmaceutical care models that exist today, with further evolution and change expected going forward. The ultimate goal is an integrated system of evidence-based total health outcomes where rational and timely product and service decisions can be made. Only systems that can contribute to this goal will be able to participate in the future.

	While this exciting and rapidly evolving segment of pharmaceutical care offers great opportunity for the pharmacy services industry, all participants will be significantly challenged by the dynamics driving the specialty business models of tomorrow.

	1. Center for Studying Health System Change. 2003 community tracking study household survey.

October 2010

Biosimilars: Could This Be a Pearl in the Patient Protection and Affordable Care Act?

Introducing Specialty Pharmacy Times: Seizing the Moment

Risk Evaluation and Mitigation Strategies in the Specialty BioPharma Market

The Special Definition of Average Manufacturer Price

Optimism and Opportunity

Near-Term Specialty Pipeline Highlights October 2010

CSL Behring's Privigen

Life in a Specialty Pharmacy

Upcoming Fall/Winter Meetings

What Will Drive the Specialty Pharmacy Models of Tomorrow?

Current Trends in IG Therapy

Navigating the Perils of Fair Market Value

Continuing Education for the Specialty Pharmacist

Rheumatoid Arthritis Watch

Oncology Watch

Multiple Sclerosis Watch