Experts propose restricting trademarks on accelerated approval drugs to speed confirmatory trials

Manufacturers might be incentivized to speed up completion of confirmatory trials for their accelerated approval drugs if they are restricted from using a brand name until the drug is granted full regulatory approval by the US Food and Drug Administration (FDA), according to a recent Viewpoint article published in JAMA Health Forum.

“Under current regulations, manufacturers can begin marketing a product once it receives accelerated approval, even if its safety and efficacy have not been verified,” Catherine S. Hwang, of Oregon Health and Science University, and S. Sean Tu, of the West Virginia University College of Law, wrote in their paper. “From a business perspective, manufacturers lack sufficient incentives to complete these confirmatory trials.”

The authors called attention to the number of accelerated approvals where a negative confirmatory trial has led to the eventual withdrawal of the drug and said there is a “need to develop incentives for manufacturers to promptly complete their mandatory postapproval studies.”

Manufacturers currently have an incentive to keep a drug that has received accelerated approval on the market for as long as possible, and little incentive to complete confirmatory trials mandated by FDA, the authors said. (RELATED: Study: 'Little incentive’ for drugmakers to complete confirmatory trials for accelerated approvals, Regulatory Focus 29 August 2022)

Notably, FDA recently published a draft guidance that clarifies the agency’s position on when it considers a confirmatory trial underway. The agency said a confirmatory trial is considered underway when it has a completion date “consistent with diligent and timely conduct of the trial,” and plans for postapproval conduct by the sponsor offer “sufficient assurance to expect timely completion of the trial,” and the confirmatory trial has started enrolling patients. (RELATED: Accelerated approval: FDA explains when it considers confirmatory trials underway, Regulatory Focus 10 January 2025)

Restricting trademarks for accelerated approval drugs

Hwang and Tu said that creating an investigational drug name for an accelerated approval drug until it is granted full regulatory approval by FDA would make it clear that a drug is investigational, and prohibiting the manufacturer from using a brand name or generic name for the drug would make marketing the drug more challenging. The investigational name may also cause payers to think twice before paying a premium price for an accelerated approval drug.

“[T]he absence of a brand or generic name delivers a powerful message to clinicians, payers, and patients that the drug has not been fully approved by the FDA as safe and effective,” the authors said.

In the case of Biogen’s Aduhelm (aducanumab), the authors said, the drug was priced at $56,000 per year, and the drug’s manufacturer had 9 years to complete follow-up studies. Hwang and Tu argued that the manufacturer “may not have been able to justify such a high price” if they were forced to use an investigational drug name. (RELATED: FDA defends Aduhelm's accelerated approval, while others call for reform, Regulatory Focus 14 July 2021)

“This strategy would be especially effective for new molecular entities, defined as treatments entering the market for a primary indication under accelerated approval status, in which the brand and generic names would not yet exist,” the authors said, noting that 86% of unique molecular entities had primary indications that received accelerated approval. “For secondary indications, we propose that the drug be referred to by its investigational name solely for its new accelerated approval indication until full regulatory approval is granted.”

Hwang and Tu also called attention to how drugs granted accelerated approval continue to increase in price and noted that Medicare spent $11.1 billion on accelerated approval medications between 2012 and 2017. “These costly therapies raise ethical concerns about paying for medications that may not be safe or efficacious,” they said.

While manufacturers tend to have the financial responsibility for Phase 3 trials, “manufacturers using the accelerated approval pathway can begin profiting after receiving accelerated approval, even if the indication is eventually withdrawn,” the authors said. “Much of this cost is passed down to patients. This is particularly problematic if the patient derives no clinical benefit because the expensive treatment is later removed from the market.”

Solutions like fines and pledges to voluntary withdraw a drug prior to its approval do not motivate manufacturers to complete confirmatory trials, the authors said, and FDA has not issued a fine to a manufacturer for violating postmarketing requirements despite having the ability to do so.

“[T]he current regulatory process governing the use of these treatments carries important unintended consequences, leading to potential harm for medications subsequently deemed ineffective,” Hwang and Tu wrote. “Leveraging trademarks could encourage manufacturers to promptly complete postapproval studies, supporting the FDA’s mission to approve only safe and effective medications while minimizing exposure uncertainty and likely lowering costs for patients during the approval process. This approach would also make it clear to all stakeholders, including clinicians and patients, that the drug has yet to be proven safe and effective, thereby supporting an evidence-based approval process.”

Enough of an incentive for manufacturers?

The idea of giving a drug an investigative name and prohibiting use of a brand or generic name until full approval is interesting, offers “a major incentive for pharma to move forward in a timely fashion after accelerated approval, and “has a good chance of working,” Joel S. Perlmutter, , professor of neurology at Washington University School of Medicine in St. Louis, told Focus.

“Currently, pharma has almost no incentive to do so since they can market their drug and generate substantial revenue while ‘working’ on the mandated follow-up study,” he explained.

Perlmutter, who was one of three FDA advisors to resign from the Peripheral and Central Nervous System Drugs Advisory Committee in the wake of FDA’s controversial accelerated approval of aducanumab, said he agrees giving the drug an investigative name “more clearly identifies the drug as not fully approved with still uncertain safety and efficacy,” and that third party payers might give greater pause before paying for accelerated approval drugs prior to full regulatory approval. In turn, that would incentivize pharmaceutical companies to complete confirmatory trials.

“The revenue easily exceeds any potential penalty for lack of timeliness in completing the study and such penalties are not levied,” he said.

Concerning the cost of covering accelerated approval drugs through the Centers for Medicare & Medicaid Services (CMS), Perlmutter said coverage decisions seem to be on a case-by-case basis. CMS hesitating to cover a drug for Medicare beneficiaries, for example, would spur manufacturers to complete any subsequent studies, and private insurers would be likely to follow suit.

“The clearly defined investigat[ive] status would help counter-balance pressure from advocacy groups that are frequently influenced by pharma, but not always,” Perlmutter said. On the other hand, a drug that has a clear clinical benefit for patients in a dire situation would be impacted by slowing distribution of the drug. Drug distribution would also be “far less equitable,” he noted, and likely limited to people who could pay for the drug privately.

“If the need was truly critical and the potential efficacy outweighed the risk, the drug would still be available,” he said. “The bottom line is that I do believe that this would incentive pharma to complete the trials.”

JAMA Health Forum Hwang et al.

Experts propose restricting trademarks on accelerated approval drugs to speed confirmatory trials

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