FDA Revokes Accelerated Approval of Bristol Myers Squibb’s Istodax (Romidepsin) for Peripheral T-Cell Lymphoma

Compiled by | Li Tom

On May 6, the U.S. FDA officially announced the withdrawal of the approval for Bristol-Myers Squibb's injectable Istodax (romidepsin) for the treatment of peripheral T-cell lymphoma (PTCL). Additionally, due to the failure of Teva's 505(b)(2) oncology drug in confirmatory trials, the FDA also revoked the drug’s application eligibility.

Despite the rejection of this accelerated application, Bristol-Myers Squibb's Istodax has still been approved for the treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy.

Notably, in August last year, after missing the primary endpoint of progression-free survival in a confirmatory Phase III clinical trial, Bristol-Myers Squibb announced the withdrawal of Istodax for the treatment of peripheral T-cell lymphoma from the U.S. market.

Romidepsin is a histone deacetylase inhibitor (HDACi), an epigenetic therapy, and belongs to the class of histone deacetylase inhibitor anticancer drugs. It was developed by Celgene Corporation and was approved by the FDA in 2009 and 2011 for patients with cutaneous T-cell lymphoma and peripheral T-cell lymphoma who have received at least one prior systemic therapy.

Among the drugs granted accelerated approval by the FDA, oncology drugs have always been the main force, while a large number of drug applications have been either forced or voluntarily withdrawn due to trial failures.

In February 2021, AstraZeneca's Imfinzi indication for bladder cancer was withdrawn by the U.S. FDA.

In March and July 2021, the indications for Merck's Keytruda in treating small cell lung cancer and gastric cancer were withdrawn by the U.S. FDA.

In June 2021, the indications for Bristol-Myers Squibb's Opdivo in treating small cell lung cancer and liver cancer were withdrawn by the U.S. FDA.

In March and August 2021, Roche's Tecentriq indications for the treatment of bladder cancer and breast cancer were withdrawn by the U.S. FDA.

In October 2021, the indication for balstilimab, developed by Agenus, to treat cervical cancer was withdrawn by the U.S. FDA.

Earlier this year, Gilead's Zydelig had its two lymphoma indications withdrawn as well.

Regarding the reasons leading to this outcome, these drugs initially received FDA accelerated approval but were ultimately rejected due to failed confirmatory trials. In particular, the Alzheimer's drug Aduhelm has been highly controversial since the day it was approved. Accelerated approval is a process used by the U.S. FDA to expedite the availability of drugs that treat serious conditions and have significant advantages over existing treatments, allowing patients to receive treatment as soon as possible. However, the U.S. health and pharmaceutical sectors have now expressed strong doubts about the FDA’s accelerated approval process.

After accelerated approval, pharmaceutical companies still need to conduct clinical studies to confirm the expected clinical benefits. If the confirmatory trial does not show that the drug provides clinical benefit, the FDA will remove the drug from the market. In some cases, post-marketing clinical validation trials proceed slowly or the drug is proven ineffective, and in many cases, the FDA takes a long time to make a decision to withdraw the drug (it took ten years for Istodax’s accelerated approval withdrawal), ultimately leading to patients receiving ineffective treatment and payers incurring significant financial losses.

An increasing number of failed cases suggest that the U.S. FDA needs to implement more significant reforms to the accelerated approval process, such as setting deadlines for confirmatory trials or revising the conditions for drugs entering the accelerated approval pathway.

Reference Source: Over 10 Years Later, FDA Officially Pulls a BMS Accelerated Approval, and a Teva Copycat Falls with It