The necessity to update and alter the FDA’s now-contentious rapid approval strategy is highlighted by the protracted, complicated FDA process to discontinue commercialization of medications that do not demonstrate safety and efficacy in mandated post-approval confirmatory studies. Over the past 30 years, this endeavour has been successful in delivering a number of critical therapies to patients more quickly. However, the recent decision by the advisory committee to recall Makena from the market as a result of its inability to show advantages for patients demonstrates how challenging it is for the regulators to make sure that such medications promptly record safety and efficacy.
A confirmatory trial was unsuccessful in verifying earlier findings after Makena was authorised more than ten years ago as a therapy to reduce the risk of premature delivery in individuals thought to be at miscarriage risk. Covis Pharma, the manufacturer and distributor of Makena, has opposed removal despite this, claiming that some high-risk patients still require the treatment. The FDA’s independent expert panel, however, voted 14-1 in favour of the agency’s decision to cease sales of the therapy, paving the way for the agency to move forward with its protracted quest to remove an accelerated drug from the market that has failed to demonstrate effectiveness.
The FDA’s approval of Biogen’s Aduhelm to treat Alzheimer’s disease in 2021 served as the spark for the discussion over accelerated approval. This choice led to a number of reform recommendations to make sure sponsors carry out necessary confirmatory research and publish their findings. At meetings in April 2021 and September 2022, the FDA’s Oncologic Drugs Advisory Committee (ODAC) also brought up the problem, criticising dangling approvals for cancer therapies. This led a few makers to pull back certain clear signs and others to redouble their efforts on confirmatory studies.
In a report released in September 2022, the Office of Inspector General (OIG) of Health and Human Services (HHS) discovered that more than one-third of early authorizations missed deadlines for concluding confirmatory studies. Additionally, the FDA had trouble getting some therapies taken off the market, which resulted in significant costs to insurers, Medicare, and Medicaid. According to the OIG, Medicaid recently spent $700 million on Makena, so it is critical to provide the FDA with the resources it needs to manage the rapid approval programme.
In response to FDA concerns, Congressional leaders put up legislation requiring funders to have confirmation trials underway before receiving an early approval. Additional changes are intended to make it easier for the FDA to revoke an approval if new study data fails to prove efficacy within a specific time frame. In order to satisfy strict deadlines for Congress to pass the funding measure, these and other measures that were initially incorporated into the bill to renew FDA user fees were removed. On Capitol Hill, efforts to include faster approval changes in proposed legislation continue, although the likelihood of adopting regulatory reform measures is dimmed by the constrained Congressional schedule.
However, given that drug pricing and benefits continue to be in the news, more control of the fast approval procedure seems imminent. Health plans and insurers are now closely examining the costs and use of treatments with provisional approval status after Medicare decided to restrict coverage of Aduhelm. The cancer community and many patient illness groups are eager to keep the rapid approval programme, but they understand that the FDA should have the authority to eliminate drugs whose backers are either unable or unwilling to prove initial efficacy. The Project Confirm effort of the FDA’s Oncology Center of Excellence (OCE) intends to put pressure on sponsors to deliver post-approval data promptly and to remove drugs from the market when post-approval trials fall short of confirming benefit or are not properly carried out.
The FDA is under pressure to stop marketing Makena despite the fact that there is no effective alternative treatment for pregnant women who are at risk of miscarriage. This is done in order to preserve confidence in the accelerated approval programme, which was formed 30 years ago and is attributed with facilitating access to more than 300 cancer and serious condition treatments. Recently, the FDA has acted to withdraw the approvals of about 35 medications, the majority for particular indications. It is opposed to keeping Makena on the market, even for a brief period of time, as doing so may persuade other sponsors to postpone confirmatory tests and disregard agency guidelines in order to preserve profitable sales.
FDA Commissioner Robert Califf recently acknowledged the broad advantages of the FDA’s rapid approval approach in developing treatments to cure critical rare diseases in a presentation to the National Organization for Rare Disorders (NORD). Additionally, he pushed for quick action to lessen ambiguity around the genuine dangers and benefits of treatments that were permitted based on biomarkers and small clinical trials. Califf said more cooperation is required to create a system of evidence production that gives the verification of benefits and hazards across years.