Bristol Myers Squibb and 2seventybio, Inc. announced the U.S. Food and Drug Administration (FDA) will convene a virtual meeting of the Oncologic Drugs Advisory Committee (ODAC) on March 15, 2024. The ODAC is anticipated to review the overall survival (OS) secondary endpoint data from the Phase 3 KarMMa-3 study to support their supplemental Biologics License Application (sBLA), or in other words, drug approval, for triple-class exposed relapsed/refractory multiple myeloma patients.

What is an ODAC meeting and why are they necessary? 

According to the Friends of Cancer Research website, the Oncologic Drugs Advisory Committee, or ODAC, is the advisory committee responsible for making recommendations concerning new cancer drugs. Its membership includes experts in general oncology, pediatric oncology, hematologic oncology, immunologic oncology, biostatistics, and other related fields.

Not all drugs go through ODAC; in fact, it's only when there are data points that may be concerning, red-flag raising, or need to be explained that drug companies will request an ODAC before officially submitting their application for drug approval. Most therapies go straight to the FDA for possible approval. 

According to the FDA.gov website, the committee consists of 13 voting members including the Chair. For myeloma ODACs, members of the ODAC and the Chair are all selected by the Commissioner or designee from people knowledgeable in the fields of hematologic oncology, general oncology, pediatric oncology, and other related professions. Most of the chosen physicians will not be myeloma experts. 

The core of voting members can include one technically qualified member, selected by the Commissioner or designee, who is identified with consumer interests (in this case, BMS and/or 2seventybio, Inc. interests) and is recommended by either a group of consumer-focused organizations or other interested persons.

In addition to the voting members, the Committee may include one non-voting member who is identified with industry interests. Patient advocates can be part of multiple myeloma therapy investigating ODACs.

The committee reviews and evaluates data (in this case, the data they are to review is anticipated to be the secondary endpoint overall survival data) concerning the safety and effectiveness of the marketed and investigational cancer drug therapies and makes appropriate recommendations to the Commissioner of Food and Drugs. 

The FDA receives the recommendation (yes it should be approved, no it should not) but does not have to base its decision of approval on the ODAC committee's suggestion. It simply gives them more information to work with when considering the drug's approval or not. 

Patients can attend the meeting and speak for or against the drug. It is a public meeting and anyone can comment during the meeting, as most of it is a discussion between those who conducted the clinical trial and those who are reviewing the data. 

What is Abecma? 

According to the Bristol Myers Squibb website, Abecma is a CAR T cell therapy that recognizes and binds to the B-cell maturation antigen (BCMA) on the surface of multiple myeloma cells, leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Abecma is the first-in-class BCMA-directed CAR T cell immunotherapy approved by the U.S. FDA for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio. The companies’ broad clinical development program for Abecma includes ongoing and planned clinical studies (KarMMa-2, KarMMa-9) for patients with multiple myeloma.

Abecma was recently approved in Japan for patients with relapsed or refractory multiple myeloma who have received at least two prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody based on the KarMMa-3 study, making it the first CAR T cell therapy to receive regulatory approval for use in earlier lines of therapy for patients with relapsed and refractory multiple myeloma. 

Why does the Phase 3 KarMMa-3 study need an ODAC meeting? 

ODAC meetings are a great place to review data points from a clinical trial before going to the FDA for approval. In this case, the overall survival rates from the KarMMa-3 study are going to be reviewed. 

The KarMMA-3 study results were presented at the 2023 American Society of Hematology (ASH) meeting and included information regarding the overall survival rates.

The study found that the average survival time (median overall survival or OS) for patients who received Abecma was 41.4 months, and the other arm of patients who received the standard-of-care treatment had an average survival time of 37.9 months. 

The overall survival benefit did not seem statistically significant when looking at the data. 

Conclusion

Stay tuned to learn whether or not the ODAC recommends Abecma to be approved for myeloma therapy. Remember, whether or not the ODAC recommends Abecma for triple-class exposed myeloma patients, the FDA will still make an independent decision on whether or not the drug should be approved. 

If approved, Abecma (one of the CAR-T products for multiple myeloma) would be available for multiple myeloma patients who have been exposed to a proteasome inhibitor (such as bortezomib or carfilzomib), an immunomodulatory drug (such as lenalidomide or pomalidomide) and a monoclonal antibody (such as daratumumab).

We are in the golden age of myeloma research, and we look forward to seeing the continued progress and improvement of multiple myeloma treatment.