BioPharma, Policy

bluebird, BMS hit roadblock as FDA delivers refuse-to-file letter for myeloma CAR-T

The FDA requested supplemental documentation related to chemistry, manufacturing and controls rather than new clinical or preclinical data. The companies plan to resubmit the application and request a priority review by the end of July.

By Alaric DeArment on May 13, 2020

Buildings 1 and 2 of the FDA campus

Two companies looking to market a CAR-T cell therapy for multiple myeloma encountered a delay as the Food and Drug Administration highlighted documentation issues in their regulatory application seeking approval of the therapy.

Cambridge, Massachusetts-based bluebird bio and New York-based Bristol-Myers Squibb said Wednesday that the FDA had sent them a refuse-to-file letter Monday night in response to their application for idecabtagene vicleucel, or ide-cel, which has potential to become the first approved CAR-T for multiple myeloma. The companies said they plan to resubmit their application no later than July.

In the letter, also known as an RTF, the FDA stated that upon preliminary review, it required more detail in the application’s chemistry, manufacturing and control, or CMC module in order to complete its review. The agency did not request further clinical or non-clinical data. In a financial regulatory statement, bluebird said that the FDA had told the companies that it needed supplemental information detailing the validation and control processes used in the lentiviral vector and drug product manufacturing processes for ide-cel.

Shares of bluebird were down more than 5.5% in premarket trading on the Nasdaq immediately following the news. BMS’ shares moved only slightly on the New York Stock Exchange. Bluebird’s shares remained down 4.6% in early afternoon trading, while BMS’ were down by three-quarters of a percentage point.

The news comes just two days after bluebird announced that BMS would pay it $200 million to buy out its milestone and royalty obligations for markets outside the U.S. The companies filed for FDA approval at the beginning of last month.

In a conference call with investment bank analysts, bluebird executives sought to reassure investors about ide-cel’s regulatory prospects.

“This was very specific to CMC, and there was no suggestion or discussion of any kind that relates to any of the clinical information or the clinical dossier,” bluebird CEO Nick Leschly said during the call, in response to a question of whether there was anything in the letter to indicate that the application could encounter further hurdles later on. “We have no reason to believe that there’s a ‘second shoe,’ if you will, out there.”

Leschly also said that the RTF would not affect bluebird’s regulatory filing plans for other product candidates.

In a note to investors, RBC Capital Markets analyst Luca Issi called the delay “unfortunate,” but wrote that the quick turnaround for refiling was a silver lining. And given that RBC doesn’t anticipate sales of ide-cel to start until the fourth quarter of next year, he added that the delay had no material impact on the bank’s model.

The companies’ approval application includes positive data from the Phase II KarMMa trial that were presented in December at the American Society of Hematology meeting in December. Updated data will be presented at the virtual American Society of Clinical Oncology meeting. Ide-cel works by targeting BCMA, an antigen widely expressed on the surface of myeloma cells. Johnson & Johnson is also developing a CAR-T cell therapy for multiple myeloma that targets BCMA.

In a note, Cowen analyst Yaron Werber wrote that the RTF for BMS and bluebird now “significantly” shrinks ide-cel’s lead in the race to the market relative to J&J’s therapy, JNJ-4528, which also showed strong data at the ASH meeting. J&J in-licensed its CAR-T from Nanjing, China-based Legend Biotech.

Photo: FDA (via Flickr, not copyright protected)