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Expanded Access Using Named Patient Programs

Neelima Firth, M.B.A. Why should we consider utilizing expanded access programs for a product? The objective of this white paper is to provide you with key background information on expanded access programs so that you may decide if an expanded access program should be part of your prelaunch commercialization strategy. There are several reasons for manufacturers to choose to invest in expanded access programs. These programs are a useful component of a global commercialization strategy, they may contribute to new revenue streams and these programs can shape physician experience, insight, and relationships globally. This white paper delineates the following: The key features of expanded access programs The benefits of expanded access programs to manufacturers, patients and their physicians The legal and regulatory framework surrounding expanded access programs in Canada and, more briefly, in the United States, Australia and the European Union This white paper also includes best-in-class recommendations for the use of expanded access programs. Introduction Oftentimes, patients with serious or immediately life-threatening diseases or conditions, who have tried approved therapies without success, are interested in investigational therapies. These patients and their treating physicians are very interested in accessing drugs under development, especially if the early results of clinical trials are encouraging. Notably, several organizations, including the Abigail Alliance, have lobbied governments to make access to investigational medicines easier for these patients and their physicians. The most common way for a patient to receive an investigational medicine is as a registered participant in an approved clinical trial. However, many patients are not eligible to participate in a clinical trial due to the trial�s inclusion and/or exclusion criteria or because of geographic location. Through expanded access programs, drug companies can provide these patients with drug therapies that are still under investigation. What are Expanded Access Programs Expanded access programs provide patients with early access to investigational or unavailable drugs when they are not eligible for a clinical trial. These can be called early access protocols, �compassionate use� programs, named patient programs or single person INDs. Some expanded access programs allow for intermediate-size groups of patients with similar treatment need who do not qualify to participate in a clinical trial. A named patient program is a specific type of expanded access where a physician can access a product for a particular �named� patient. Each request is considered on a case-by-case basis, which is why this approach is referred to as a �named patient� program. In general, named patient programs are also known as expanded access programs. In this paper, we will use expanded access to refer to: Early access Named patient Compassionate use Single Person IND Physician The treating physician makes the clinical judgment that no comparable or satisfactory alternative approved therapy is currently available for a given patient and that the probable risks from the experimental drug are not greater than the probable risks from the disease or condition itself. Examples of potential benefits that might justify expanded access include the potential for longer survival or substantially improved quality of life. Disease These programs are generally intended for patients who present with a serious or immediately life threatening disease or condition who lack other therapeutic options and who may benefit from the investigational therapy. For this reason, expanded access programs are often associated with cancers or diseases that occur rarely or in very small patient populations. In reality, many serious diseases may be appropriate for an expanded access program. Drug manufacturer/Sponsor The drug manufacturer developing the medicine has the authority to decide whether to provide an investigational drug to a patient who is not enrolled in the clinical trial. The availability of such programs can be limited by the drug supply, patient demand, or other factors. The manufacturer may develop a protocol or create specific criteria for use of the product in an expanded access program. The drug manufacturer develops the criteria for approval or denial of expanded access requests and can require physicians to submit any documentation or clinical evidence that the manufacturer believes is appropriate. Reimbursement A country�s legal and regulatory framework permits drug manufacturers to charge for an investigational drug when it is provided through an expanded access or named patient program. The U.S. Food and Drug Administration (FDA) released two rules on August 12, 2009, regarding �expanded access to investigational drugs for treatment use� and �charging for investigational drugs under an investigational new drug application.� These new rules clarify the circumstances under which a manufacturer can charge patients for an investigational drug and the types of costs for which manufacturers may charge patients. Canada has the Special Access Program which allows manufacturers to sell investigational products. Australia has the Special Access Scheme where physicians can proactively apply for investigational medicines. The EU has a general framework that allows access. However, each member states of the EU also have their own requirements, most require the patient, hospital, or national insurance system to pay the costs of investigational drugs provided through expanded access programs. An example is that in Spain, manufacturers are expected to provide the products free of charge to patients. In other member states, manufacturers can charge for product. Key Benefits Expanded access programs enable companies to provide early market access to important medicines before obtaining regulatory approval for these drugs. When a drug is in the prelaunch phase or has been approved and launched in the United States, the drug�s manufacturer is likely to receive requests for the drug from around the world. The company can fulfill this demand, when appropriate, by using an expanded access program. Expanded access programs can also provide a company with additional revenue, insight into the product�s value to physicians and patients, and new relationships with key opinion leaders across the globe. Legal and Regulatory Framework Most countries have a system to allow expanded access to investigational drug therapies and an authorization process for this system which is intended to protect patient safety. These programs are referred to as compassionate use, expanded use, or named patient supply programs. All countries institute substantial legal and regulatory requirements for the use these programs. Each country�s regulatory board decides whether sufficient evidence of a drug�s safety and effectiveness is available to support expanded access use. Regulatory agencies also ensure that the expanded access use will not interfere with the completion of clinical trials or approval of the product in that country. In the United States, expanded access programs have been available since 1987. In August 2009, the Food and Drug Administration clarified the circumstances under which investigational products can be made available to patients and the types of charges for these products that manufacturers can make. Canada�s Special Access Programme (SAP) provides access to non-marketed products. In some cases, these products are on the market in the United States or EU but, for business reasons, the manufacturer has decided not to market the product in Canada. The SAP gives physicians access to non-marketed products for patients with serious or life-threatening illnesses. The SAP also allows manufacturers to sell the products Australia�s Special Access Scheme, like the U.S. and Canadian programs, allows physicians to use unapproved products for life-threatening diseases. The EU has a regulatory framework (described in Article 5 of Direction 2001/83/EC) for the supply of unapproved medicines in response to unsolicited requests. In 2004, the EU added �compassionate use� programs in regulation 726/2004. Each European country has its own design for its compassionate use program and its own national regulations regarding the import of prelaunch medicines. The European Medicines Agency program approves prelaunch drugs through a centralized process. However, reimbursement decisions can take many months in some member countries, and this can sometimes delay patient access to drugs. In most cases, the physician is legally liable for the drug�s use. In some countries, such as the United Kingdom, the company is responsible for issues related to the product and the physician is responsible for patient clinical care issues. Special Access Program in Canada (SAP) Under Canada�s Food and Drugs Act, Health Canada is authorized to regulate the safety, efficacy, and quality of therapeutic products. Prior to market authorization, access to a drug is usually limited to clinical trials sponsored by a manufacturer and authorized by Health Canada through a clinical trial application (1). When a drug is not available through a clinical trial, Health Canada (the Canadian government�s health ministry) may allow an exemption from the Food and Drugs Act and its regulations to permit the sale of an unauthorized drug for a medical emergency. According to the Food and Drugs Act, companies may provide the drugs for free or they may charge patients for these drugs. Health Canada has permitted the sale of unauthorized drugs for medical emergencies since 1966. In the 1990s, Health Canada expanded the term �medical emergency� to include serious and life-threatening conditions. Special access to unauthorized drugs is intended for serious or life-threatening conditions for which conventional therapies have failed, are unsuitable, or are unavailable as marketed products or through enrollment in clinical trials. Emergency access is intended to be exceptional. Roles and Responsibilities Health Canada The SAP decides whether to authorize or deny SAP requests from doctors on a case-by-case basis. The agency takes into account the nature of the medical emergency, the availability of currently marketed alternatives, and the safety and efficacy of the requested medicine. If Health Canada grants access to the requested drug, the physician agrees to report on the use of the drug, including any adverse events. The SAP grants access to only a limited quantity of the requested drug and for a limited time period only. Access to drugs that are currently undergoing regulatory review is also limited until the review is complete. Physician or Practitioner The physician initiates a request and ensures that the decision to prescribe the drug is supported by credible evidence from clinical publications, investigator brochures, or prescribing information from another country. They are required to account for all drug supplied and to report to SAP and the manufacturer the outcomes of usage and any adverse events. Manufacturer The key decisions are whether to sell the drug to physicians through the SAP. A manufacturer is under no obligation to sell an unauthorized drug and the SAP cannot compel a manufacturer to do so. The manufacturer also decides the price of the drug and may consult with Canada�s Patented Medicine Prices Review Board if necessary. They can also imposes conditions on the drug�s sale to ensure that it is used in accordance with the latest information available. Manufacturers may: Request additional information on the patient for whom the physician has requested the drug. Offer a protocol for using the drug. Provides all relevant and updated information to the physician, such as an investigator brochure or prescribing information. Process Consideration is the process by which the SAP reviews the request and decides whether to authorize it. The Consideration Matrix (Figure 1) summarizes the factors that the SAP takes into account to ensure that an emergency exists and credible data are available to support the request. Historic Examples of Applications of the Expanded Access Programs Erbitux� (cetuximab) was available through the SAP prior to its commercialization in Canada in October 2008. Although Health Canada approved the product in 2005, Erbitux did not enter the Canadian market at that time because the Patented Medicine Prices Review Board and Bristol-Myers Squibb could not agree on the price for the drug. While that discussion was ongoing, some patients had access to the product through the SAP (3, 4). A number of blood products, including Haemocomplettan� (fibrinogen), Factor VII concentrate, and Factor XI concentrate, are available through the SAP (5). Generex Biotechnology Corporation received SAP authorization from the Therapeutic Products Directorate of Health Canada for a patient-specific, physician-supervised treatment of type 1 diabetes mellitus with Generex Oral-lyn� (oral insulin ). Generex regarded this information as important enough to list in its U.S. Securities and Exchange Commission filing in May 2008 (6). In some cases, a product that is not licensed in Canada is routinely used in that country to treat serious diseases, such as cancers. An example is Eloxatin� (oxaliplatin), a chemotherapy drug that has become the standard of care for colorectal cancer. The manufacturer, Sanofi-Aventis, has distributed this product in Canada since 1999 through the SAP program. It was only in 2007 that Sanofi-Aventis decided to seek a license from Health Canada to market the drug (7). Thalidomide has been available in Canada through the SAP for treating multiple myeloma. Because the drug was not licensed and was only available in Canada through the SAP, the price was not regulated. In 2008, the price increased nine-fold. That same year, Canada�s Patented Medicine Prices Review Board ruled that it had jurisdiction over the drug and determined that its price was excessive. The board therefore imposed retroactive price controls on thalidomide (8 ). In 1990, Genzyme developed Ceredase� (alglucerase) for Gaucher disease and distributed the product outside the United States on a named patient basis. In 1991, Ceredase received marketing approval in the United States (9). Genzyme now offers Mozobil� (plerixafor), approved in the United States for non-Hodgkin�s lymphoma and multiple myeloma in December 2008, to patients in other countries through expanded access programs (10, 11) , Best-In-Class Recommendations and Challenges Expanded access programs can provide a number of important benefits to patients, physicians, and drug manufacturers. These programs offer early market access to potentially life-saving or life-improving drug therapies for appropriate patients before these therapies receive regulatory approval. The programs also provide market access to orphan drugs for patients with rare disorders. An expanded access program strategy should be considered as part of a market access strategy for a product or portfolio. A company�s decision to offer such a program needs to take into consideration the disease requiring treatment. An expanded access program is only appropriate for drugs used for serious, debilitating, and immediately life-threatening diseases (such as cancer, epilepsy, AIDS, and diabetes) in which an unmet need for therapy exists . Beef it up and ensure part of selling many products. Describe product portfolio. Elective not inclusion, constraints broad Once a company decides to create an expanded access program, it needs to establish clear business rules, such as which drugs to make available, the criteria for providing the drugs, and whether to charge for the drugs or offer them at no cost to patients. If a company plans to charge for a product, it must decide on the appropriate price as part of its worldwide pricing strategy. Any expanded access program exists in a highly regulated environment. Manufacturers must make important legal, regulatory, and clinical decisions for each drug. Companies therefore need standard operating processes for reviewing and approving product requests and shipping products. Because companies must review and approve product requests on a case-by-case basis, they need clear and adequate documentation at each step of the process. Companies that choose to utilize expanded access programs also need a distribution process for the products; such processes are often outside a company�s normal ordering and shipping channels. Because of the mandated legal, regulatory, and clinical framework, companies must report, monitor, and audit the processes on a regular basis to ensure that their processes are aligned with corporate strategy, clinical advancements, and regulatory requirements. Because of all of these requirements, manufacturers need to allocate adequate internal resources to their expanded access programs. Expanded access programs require significant management to establish. The decision to implement such a program must therefore take into account the company�s clinical, regulatory, and market access strategy for its products. Companies stand to gain many benefits from providing early access to a product, including the creation of a group of patients and physicians who are already aware of the product�s benefits and can support launch activities, as well as an early revenue stream. Conclusions An expanded access program is an important part of a manufacturer�s global commercialization strategy. The benefits of such programs to manufacturers include expanded global reach, the potential for the creation of new revenue streams, and the ability to gather important clinical experience and insight. Patients value these programs because they receive needed treatment for life-threatening or debilitating illnesses when all other therapies have failed. Countries encourage these programs to provide their citizens with access to life-saving treatments. regulatories The Aequitas Group is a consulting firm that can help companies develop global reimbursement and commercialization strategies. The Aequitas Group has expertise in evaluating and successfully executing a range of expanded access patient programs as part of global commercialization strategies. References 1. Health Canada. Special Access Programme for Drugs. Guidance Document for Industry and Practitioners. Effective date: January 28, 2008. http://www.hc-sc.gc.ca/dhp-mps/acces/drugs-drogues/sapg3_pasg3-eng.php#4 2. Health Canada. Special Access Programme. Special Access Request Form A, and Future Use Request Form B, Follow-up Form C. http://www.hc-sc.gc.ca/dhp-mps/acces/drugs-drogues/index-eng.php 3. Bristol Myers Squibb. BMS Canada Commercializes Erbitux for Advanced Colorectal Cancer. Press release. October 29, 2008 http://www.bmscanada.ca/bms/news/?news_id=2454 4. FiercePharma. BMS Swallows Canada�s Erbitux Price. April 29, 2008. http://www.fiercepharma.com/story/bms-swallows-canada-s-erbitux-price/2008-04-29#ixzz0PEvgqYNZ 5. Canadian Blood Services. Special Access Programme (Health Canada). February 24, 2009. http://www.bloodservices.ca/CentreApps/Internet/UW_V502_MainEngine.nsf/resources/CustomerLetters09/$file/SAPTable2009-02-24.pdf 6. Steffens RJ. Generex Biotech�s Oral-lyn granted special access authorization by Health Canada. Seeking Alpha. May 5, 2008. http://seekingalpha.com/article/75652-generex-biotech-s-oral-lyn-granted-special-access-authorization-by-health-canada 7. Priest L. Trade gambit doubles cost of cancer medicine. Reprinted from the Globe and Mail, May 25, 2007, by the Colorectal Cancer Association of Cancer. http://www.colorectal-cancer.ca/en/news-and-resources/trade-medicine/ 8. Priest L. Ottawa moves to reduce price of drug after cancer patients complain of gouging. Reprinted from the Globe and Mail, January 31, 2008, by Myeloma Canada. http://www.myelomacanada.ca/docs/ottawa%20moves%20to%20reduce%20price%20of%20drug%20013108.pdf 9. Genzyme. Ebook. http://www.genzyme.com/corp/anniversary/index.html 10. Genzyme. Genzyme receives positive opinion for European approval of Mozobil. Press release. May 29, 2009. http://www.genzyme.com/corp/media/GENZ%20PR-052909.asp 11. Genzyme. European commission approves Genzyme�s Mozobil. Press release. August 5, 2009. http://www.genzyme.com/corp/media/GENZ%20PR-080509.asp If you would like to learn more about The Aequitas Group, please contact us today.