Bristol Myers takes a write-off of $ 470 million and waives the Orva-Cel CAR-T program
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Earlier this week, the U.S. Food and Drug Administration (FDA) approved Bristol Myers Squibb‘s Breyanzi (Lisocabtagene maraleucel; liso-cel) for adults with relapsed or refractory (r / r) large B-cell lymphoma (LBCL) after two or more systemic lines of therapy. Liso-cel is a CD-19 targeted chimeric antigen receptor (CAR) T-cell therapy.
The company also has a PDUFA date of March 31, 2021 for its Biologics License Application (BLA) for ide-cel, a B-cell maturation antigen (BCMA) targeted CAR-T therapy.
So it’s a bit of a surprise when Bristol Myers Squibb reported It abandoned a second BCMA CAR-T therapy, Orva-Cel, and took a $ 470 million write-off. Orva-cel was originally developed by Juno Therapeutics, which Celgene acquired for $ 9 billion before Celegene was acquired by Bristol Myers Squibb for $ 74 billion in late 2019.
The company’s head of drug development Samit Hirawat told analysts on a conference call last week that the decision would be to work with the best drugs, especially in a crowded field like BCMA.
“We have ide-cel as the front runner who has the data and has been submitted for review and approval in both the US and the EU,” said Hirawat. “If we look at the orva-cel development of the data and also look at it from the outside in relation to the landscape and the development of data, we believe that ide-cel fits perfectly with regard to further development. And the orva-cel platform will be very important for the next generation of CAR cell development and not for this particular drug itself. Therefore, we did not advance orva-cel as it is in its current form and would use the platform for the evolution of cell therapies. “
Orva-cel, short for Orvacabtagene Autoleucel, became rated in a Phase I / II EVOLVE study in mid-2020 to investigate different dose ranges of CAR T cells in patients with relapsed / refractory multiple myeloma (RRMM). Previous studies at lower doses showed an acceptable safety profile and promising clinical behavior.
At the time, Sham Mailankody, a medical oncologist at Memorial Sloan Kettering Cancer Center, said Helio, “BCMA has shown promise as a promising treatment target in myeloma, and Orva-cel is a novel CAR T-cell therapy with an optimized manufacturing process that enriches a central memory phenotype and could result in more sustained and hopefully more effective treatment in it Attitude. Initial data from the ongoing EVOLVE trial have shown promising efficacy for Orvacel treatment in patients with relapsed or refractory multiple myeloma. “
Liso-cel has been approved under the brand name Breyanzi. CAR T therapies like Breyanzi are live therapies in which T cells are taken from the patient, developed in a laboratory specifically for the patient’s cancer cells, and then re-infused into the patient where they grow and attack the cancer. It has a target lead time of 24 hours, with inpatient or outpatient management options. It is planned to roll out the therapy in a wide network of treatment centers that are certified for risk assessment and risk reduction strategy (REMS). Cytokine Release Syndrome (CRS) is as common as neurological toxicities, which is why the clinics that perform the treatments are REMS-certified so they are trained to deal with the potentially fatal side effects.
A Celgene Contingent Value Rights (CVR) of $ 9 as of December 31, 2020 Payout period passed. It was one of three required milestones for the CVR. Bristol Myers Squibb said at the time that the CVRs would then be terminated, meaning that they would no longer be solvent and could no longer be traded on the New York Stock Exchange. There were about 715 million CVR notes in circulation. If the three milestones had been met, the Notes would have paid out $ 6.4 billion to investors.
The CVR was based on FDA approval of three drugs, Zeposia, Ide-Cel and Liso-Cel. Ceposia (ozanimod) for the treatment of multiple sclerosis was approved in March 2020. The FDA accepted the approval application for biologics for ide-cel, a B-cell maturation antigen (BCMA) targeted CAR-T therapy, in September 2019 with a target deadline of March 31, 2021.
Liso-celo was originally supposed to be approved by November 16, 2020, but the pandemic blew the schedule. In November 2020, Bristol Myers Squibb stated that the COVID-19 pandemic was delaying travel for FDA inspectors to inspect a third-party manufacturing facility in Texas before the scheduled action date. But they couldn’t, a possible approval of Liso-Cel was delayed until the inspection could be completed.