The four reports include: (1) an Overview, summarizing the need for and major policy issues related to extending access to new long-acting products for HIV treatment and prevention; (2) From Laboratory to Marketplace, discussing the Food and Drug Administration (FDA) review and approval process and special considerations for long-acting products; (3) Assessing the Payer Landscape, exploring the laws and policies that shape pharmaceutical access in public and private insurance; and (4) Defining the Intended Market for New Products, addressing issues such as adherence to non-daily products, consumer and provider acceptability, and cost-effectiveness. In addition to the reports, there is also a chart of long-acting agents in development for HIV treatment and prevention.
Jeffrey Crowley opened the briefing by discussing the HIV landscape in the United States. Crowley noted that while we have made great strides in the fight against HIV, much work remains. There is more that we can do with the tools we have. We need to extend health care to more people. We need to test more. And we need to redouble our efforts to support people so that they are able to start and maintain PrEP for HIV-negative people at risk for HIV infection and antiretroviral therapy for those living with HIV. But we also must remain committed to investing in new and better tools to prevent infection and support viral suppression among people living with HIV.
Dr. Carl Dieffenbach, Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, discussed the science of long-acting HIV treatment and prevention. Long-acting products that do not require daily dosing could become available within the next few years. One product, Ibalizumab, is currently available, and several agents are in various stages of the research pipeline. While there are lessons learned from research on long-acting contraception, which has shown that less frequent dosing can lead to improved adherence, Dr. Dieffenbach remarked that long-acting products do not eliminate adherence challenges, but rather these products increase the urgency of getting individuals back for re-dosing.
Following Dr. Dieffenbach’s presentation, I provided an overview of the major policy issues related to extending access to long-acting products that are under development. These issues relate to how the Food and Drug Administration (FDA) will evaluate different products and the standard that new products will be required to meet for approval, how payers will make decisions about who has access to these products, and what impact products will have on adherence as well as what factors will influence demand for new products and the willingness of medical providers to prescribe the products.
FDA Review and Approval
Once a pharmaceutical manufacturer has a product to submit for review, the FDA will assess the safety and effectiveness of the product and consider relevant commercialization issues. The FDA will need to consider unique questions related to long-acting products, such as the potential to spur drug resistance. One circumstance in which resistance develops is when levels of the drug remain in the body for significant period of time, yet at a level below the level of effectiveness.
Within the FDA, drugs and devices are regulated by different centers. Given the variety of delivery mechanisms for long-acting products (pills, implants, injectables, rings), different products may be regulated by different, and in some cases, multiple parts of the FDA. While pills would be classified as drugs regulated by the Center for Drug Evaluation and Research, other products may contain both drug and device components and may be considered combination products. It will be important for policy makers and community stakeholders to prepare the FDA for prospective long-acting HIV treatment and prevention options, which will involve bringing together relevant parts of the FDA, and ensure expeditious review of new drug applications and that there is clear guidance for manufacturers and others on key issues.
Once a product is approved by the FDA, payers – meaning the various public and private programs that pay for health care, such as Medicaid, Medicare, the Ryan White HIV/AIDS Program (including the AIDS Drug Assistance Program or ADAP), private insurance and other programs – will have various levels of discretion to determine whether and when to make new products available. Each of these programs operates under different provisions of laws and has different rules regarding pharmaceutical coverage. Within the Medicare program, different long-acting products could be covered by different parts of Medicare and could have different access rules. The Medicare Part B program covers physician-administered drugs, and the Medicare Part D programs covers most outpatient prescription drugs; each has its own coverage requirements. Cost sharing in Medicare Part B can be significant, as beneficiaries are responsible for 20% of the Medicare approved amount for the drug and the Part B deductible applies ($183 in 2018). Unlike Medicare Part D, which has a low-income subsidy program, there is no program in Medicare Part B to provide cost sharing to low-income beneficiaries.
One issue that likely will confront ADAPs is demand that they assist clients with Medicare Part B cost sharing. As of last month, the Health Resources and Services Administration (HRSA), which administers the Ryan White HIV AIDS Program through its HIV/AIDS Bureau, released a policy clarification notice regarding ADAP coverage of Medicare Part B costs, clarifying that ADAPs can use Ryan White funds to pay for Part B premiums and cost sharing, but if ADAPs do so, they must also pay for Medicare Part D premiums and cost sharing. Previously, HRSA program guidance seemed to preclude using funds in this way, but the new guidance is good news for people living with HIV on Medicare. Various payers must consider in advance how they will evaluate new long-acting products, and federal agencies should consider how they could provide early guidance for purchasers, prescribers, and the public on how new products will be evaluated and integrated into drug formularies.
Defining the Market
Beyond FDA and payer issues, other issues relate to adherence to non-daily products, community and provider acceptability, and cost-effectiveness. It will be important to understand the range of critical issues that will influence demand for new products and the ability to adhere to therapy. A major rationale for introducing long-acting products is to support adherence. More research is needed to understand whether infrequent dosing actually strengthens adherence. Quality of life is of primary importance to many people living with or at risk for HIV, and it is important to understand how long-acting products affect quality of life. Considerations include therapeutic and non-therapeutic benefits, the possibility of side effects, injection site pain, affordability, privacy, and convenience, including the need for prescription refills, the frequency and duration of medical appointments, and whether the drug delivery can be through a doctor, nurse, or other medical provider or self-administered. Providers also have their own questions and concerns, including about drug resistance. Access to new products will be contingent on providers proscribing them. Federal agencies and others should fund efforts to actively engage with community partners and to assess attitudes, questions, and information needs among people living with or at risk for HIV and among health care providers well before products are marketed.
The views reflected in this expert column are those of the individual authors and do not necessarily represent those of the O’Neill Institute for National and Global Health Law or Georgetown University. This blog is solely informational in nature, and not intended as a substitute for competent legal advice from a licensed and retained attorney in your state or country.