ODAC Continues to Make Revolutionary Drug Recommendations During COVID-19

The Oncologic Drug Advisory Committee (ODAC) comes to the aid of the FDA for purposes of offering a multidisciplinary view of safety and efficacy data for oncologic agents. In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the discussions around recommending drugs for FDA approval have moved to a virtual format, but the protocols remain the same.

In July 2020, ODAC was called to a hearing for belantamab mafodotin- blmf (GSK2857916; Blenrep), which was first granted Priority Review by the FDA in January 2020 as treatment of patients with relapsed or refractory multiple myeloma whose prior therapies included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. After reviewing data from the phase 2 DREAMM-2 study (NCT03525678), ODAC voted 12 to 2 in favor of the drug’s FDA approval. The FDA honored the recommendation and approved the drug on August 5, 2020.

During the August 13, 2020 ODAC hearing, the topic on the docket was remestemcel-L (Ryoncil), which was granted Priority Review by the FDA in April 2020 for use as treatment of children with steroid-refractory acute graft-versus-host disease (aGVHD). Results from 2 randomized clinical trials and a single-arm study were put before the committee, and they voted 9 to 1 in favor of the drug’s approval. The FDA is scheduled to make a decision on the approval on September 30, 2020.

In an interview with Targeted Oncology, Phillip C. Hoffman, MD, professor of medicine, University of Chicago, and chairperson of ODAC, discussed ODAC operations during the COVID-19 pandemic and the most recent meetings and decisions the committee has made to influence treatments options in oncology.

TARGETED ONCOLOGY: Since that COVID-19 pandemic, ODAC has held 2 virtual hearings. What was this experience like for yourself and others on the committee? How was it different from prior ODAC meetings?

Hoffman: Traditionally, ODAC only meets on an as-needed basis, and that’s typically 3 to 4 times per year. We are called in for the cases that the FDA considers challenging, due to non-traditional study end points, for example, but, may approvals occur without ODAC’s input.

These last 2 meetings were held virtually. The first one was, we were reviewing an approval in multiple myeloma. There were some technical glitches, and because of that, the meeting lasted longer than a half a day. Other than that, it was just a matter of getting all of the committee members on the call, and the rest was very straightforward.

One of the challenges we run into with the virtual format is figuring out how everyone can share their materials. During the hearing, an FDA member wanted to display a video with his slides, but our format did not allow for that.

For the second meeting, we went all day and there were no significant glitches. I was also pleased to see over 1,000 people listening in because for our in-person meetings, there were never more than 25 people in attendance aside from the people who were presenting.

Virtually, a lot more people can participate in the meeting.

I do still prefer in-person meetings, but, I think, as an adaptation considering the state of the world, I think they did it very well. I don't think anything was lost in translation.

TARGETED ONCOLOGY: How do you anticipate these hearing evolving as the country reopens?

Hoffman: In the next 6 to 12 months, I suspect our meeting will continue with the virtual format. There is going to be hesitation for many months because the people who are involved come from all over the country. I also presume it saves a lot of money for the FDA to hold these meetings virtually. I am curious to see if they will continue this in the future, even when there’s no risk of infection. The workforce in general is looking at the need for certain people to come into the office. Again, I'm sort of old fashioned, and I like seeing people that I'm meeting with, and there's something to be said for actually being face-to-face.

TARGETED ONCOLOGY: Going more in-depth into the purpose of these meetings, can you give a key takeaway from the data brought before ODAC in July for belantamab mafodotin in multiple myeloma?

Hoffman: Belantamab mafodotin was recently approved by the FDA, and of course ODAC was involved with giving advisory to the FDA on this. The vote was strongly positive and typically the FDA goes along with ODAC’s recommendation.

I was impressed with the data with regard to how useful the drug was. I also thought the sponsor did a good job in putting the eye toxicities into perspective. Because the FDA is savvy with who they select as temporary member of ODAC, we were able to speak to some of these toxicities. We had ophthalmologists on the committee for temporary voting, and they were reassuring as well that these were not certainly not life-threatening problems and they are the sort of thing that patients would be willing to put up with to have access to a drug that is effective.

Overall, things went exactly how I thought they would go when I was reading the materials. I thought that ODAC as a whole would vote in favor of approving the drug because it didn’t seem like the ocular toxicity was such a magnitude that patients would be unwilling to take the drug.

The interest and the buzz around the drug are quite positive. I think people are happy that it got the approval.

TARGETED ONCOLOGY: How do you think this approval will impact the myeloma treatment landscape in?

Hoffman: I don’t have an expert opinion on that. The have been approvals of quite a number of myeloma drugs in the last 10 years. If you’re not an expert in myeloma, the number of options, the combinations, and how to sequence can seem complicated.

I have a sense that myeloma has become a disease that people can live a long time with. I assume that the myeloma community will find the best way to fit this new drug into their overall plans. In fact, ODAC has actually had discussions in the past about how a new drug would compare to existing drugs and, ultimately, we decided that it’s not our purview to decide.

How the physicians use and sequence drugs is up to each individual physician. Our job is just to say yes, this is a safe and effective drug.

TARGETED ONCOLOGY: Moving on to the August 13th ODAC hearing, can you share your thoughts on the data presented for remestemcel-L?

Hoffman: This was a very complicated decision for the committee. The morning sessions had a lot of science in it that many of us clinicians are not familiar with. The sponsor did do a good job in presenting that science in a way that could understood.

The key takeaway from these data were that although there had been prior randomized trials that did not show benefit, it seemed that changes had been made in the product that could have accounted for differences in activity. The bottom line was that the drug did work.

The sponsor was smart in getting Joanne Kurtzberg, MD from Duke Health. She was very articulate about explaining what these children are suffering, how serious of a problem GVHD can be and her experience with seeing this drug make a big difference. Then, we had corroboration of that from some of the members of the committee.

This was a meeting I went into not knowing how it would. The afternoon presenters who were clinicians did an excellent job of addressing the question in a forthright way. I think everyone on the committee felt that, because there were no new safety signals with this drug that were of concern and there was a need, the drug should be approved.

TARGETED ONCOLOGY: What was the key reason for your positive vote?

Hoffman: I voted yes, and I was surprised that there were an overwhelming number of members who voted yes. One member changed their vote at the end, and the vote became 9 to 1 instead of 8 to 2. That was a testament to the sponsor’s job of presenting the data and addressing the uncertainties raised by the FDA.