New Data for Odronextamab

The medical journal Annals of Oncology published some updated data on the bispecific Odronextamab last week. It will be very interesting to see the implications.

You may remember Odronextamab being in the news a few months ago. It's a bispecific antibody, attaching to the CD20 protein on a Follicular Lymphoma cell and a CD3 protein on a T cell. (Read a little more about Bispecifics here as a reminder.)   In March, the FDA denied the application for Odronextamab to be approved, but only temporarily. The treatment had been granted accelerated review in October 2023, but in March, the FDA decided that it wanted to see more data. The application had been submitted with data from phase 1 and phase 2 trials.

The results from those trial were good. In the phase 2 trial, patients with Follicular Lymphoma had an Overall Response of 82% and a Complete Response of 75%. Durability was good, to, with a median duration of response of 20.5 months and median Progression Free Survival of 20 months. Safety was a potential issue, with 100% of the 131 patients with FL experienced side effects, with 78% of them experiencing grade 3 (serious) side effects, including Cytokine Release Syndrome (in over 50% of patients in the trial), low blood cell counts, diarrhea, fever, and joint pain. 

The article in Annals of Oncology is called "Safety and Efficacy of Odronextamab in Patients with Relapsed or Refractory Follicular Lymphoma," and the results are slightly different. It's looking at 3 fewer patients than the earlier data, with an ORR of 80% (vs 82%) and a CR of 73.4% (vs 75%). Meduan PFS is about the same, and the duration of CR is 25 months.

Still, the biggest concern seems to be safety. About 16% of patients had to stop the trial because of side effects, and the numbers for Cytokine Release Syndrome, Neutropenia (low whire blood ells), and Pyrexia (fever) are high. 

The advantage of having this published in a medical journal, even if the numbers haven't changed much, is that it has gone through peer review -- other experts have seen the data and confirmed it, and potentially approved the authors' assessment of their own data ("generally manageable safety.") The authors discuss safety issues in their conclusions, and point out that the trial happened during the Covid period before vaccines, which may have affected some patients results. They also say that, based on the safety data, they plan to conduct the trial on an out-patient basis. In other words, in the phase 2 trial, patients had to go to the hospital to receive the treatment and be monitored. They think side effects are manageable enough that hospitalization won't be necessary as they expand the trial to get more data.

So it looks like there isn't enough new data here to justify FDA approval. But having it all be reviewed by outside experts, and seeing the optimistic analysis from the authors, means that we might see another application soon -- within a couple of years, certainly, maybe sooner than that. (Assuming the phase 3 trial doesn't show any new safety issues.)

So this is overall good news, even if it's mostly old news.

 We'll definitely keep an eye on this one.