Bristol Myers pulls an Istodax lymphoma use 10 years after FDA accelerated approval

Amid FDA pressure on immuno-oncology drugs that have failed confirmatory studies, Bristol Myers Squibb recently pulled two uses from Opdivo’s U.S. label. Now, the New York pharma is following suit on an aging Celgene cancer drug.

Bristol Myers has decided to withdraw Istodax’s indication as a monotherapy for peripheral T-cell lymphoma (PTCL) after at least one prior therapy, the company said Monday.

Istodax won accelerated approval in the use back in 2011 based on cancer clearance data from two single-arm clinical trials. But the legacy Celgene drug recently flopped a confirmatory phase 3 trial in newly diagnosed patients.

Bristol Myers’ move comes as the FDA works through an industrywide review of checkpoint inhibitors with accelerated approvals that haven’t proven their benefits in confirmatory trials.

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As part of the agency's campaign, Bristol Myers a few days ago said it’s voluntarily withdrawing Opdivo’s conditional nod in liver cancer patients who previously received Bayer’s standard-of-care Nexavar. An FDA advisory committee previously voted to strip the PD-1 inhibitor of that indication. Before that, the company in late December started removing an Opdivo indication in third-line small cell lung cancer after the drug failed two confirmatory studies.

It’s not immediately clear whether Istodax also fell within the scope of the FDA evaluation now that the agency has dealt with all the immuno-oncology indications it had found to be questionable.

“The company took this action in accordance with the FDA’s requirements for evaluating accelerated approvals that have not demonstrated sufficient clinical benefit,” Bristol Myers said in a statement Monday.

As for Istodax, a combination of the HDAC inhibitor and the standard four-drug chemo-containing regimen CHOP failed to outdo CHOP alone at staving off cancer progression or death in treatment-naïve PTCL patients. Patients who received the Istodax-CHOP regimen lived a median 12 months without disease progression compared with 10.2 months for the CHOP group. That improvement translated into a risk reduction of 19%, which wasn’t statistically significant.

Investigators presented the Istodax phase 3 results at last year’s American Society of Hematology annual meeting.

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As Bristol Myers points out, the PTCL space has seen more treatment options arrive since Istodax’s introduction. In 2018, Seagen’s antibody-drug conjugate Adcetris, used in combination with chemo, became the first FDA-approved drug for newly diagnosed PTCL.

Pulling the PTCL use won’t affect Istodax’s original FDA nod in cutaneous T-cell lymphoma. The removal also won’t hurt Bristol Myers’ topline in any notable way. Before the megamerger, Celgene reported that Istodax sales declined 17% year-over-year in 2018 to just $63 million. Bristol Myers doesn’t break out the drug’s sales.

Investigators have also tried to pair Istodax with Opdivo in PTCL. But that approach appears to be a dead-end after researchers noted several patients in a phase 2 trial had dramatic disease progression while on the combo.