The FDA’s Oncologic Drugs Advisory Committee (ODAC) is planning to host its first meeting under new agency commissioner Marty Makary, M.D.
As head of the FDA’s oncology department, Richard Pazdur, M.D., represents the only FDA center director on the pharmaceuticals side left from the prior administration. The biopharma industry will be looking eagerly for signs of policy consistency from the upcoming public meeting.
The next meeting will take two days on May 20 and 21, according to a Federal Register notice (PDF). Roche’s application to move Columvi up in the treatment sequence of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) for transplant-ineligible patients and Johnson & Johnson’s bid to expand Darzalex Faspro to high-risk smoldering multiple myeloma will be featured on the first day.
On the second day, external advisers to the FDA will discuss UroGen Pharma’s intravesical version of its chemotherapy Jelmyto in low-grade intermediate-risk non-muscle invasive bladder cancer and Pfizer’s request to expand the label of PARP inhibitor Talzenna to include a broader population in metastatic castration-resistant prostate cancer (mCRPC).
For Roche, the phase 3 Starglo trial showed that combining Columvi with the chemotherapy regimen GemOx significantly reduced the risk of death by 41% compared with Rituxan and GemOx in DLBCL patients who had tried at least one prior line of therapy and were not eligible for a stem cell transplant.
However, an exploratory analysis found that Columvi’s life extension benefit was entirely driven by patients outside the U.S. and Europe, and that there were more deaths within patients in the U.S. and European subgroup in the Columvi arm than those in the control.
One possible explanation could be pegged to the availability of highly efficacious later-line treatments such as CAR-T therapies. But the trial’s principal investigator, Jeremy Abramson, M.D., from the Massachusetts General Hospital Cancer Center, argued that the number of patients in that subgroup was too small to draw any conclusions.
The European Commission has approved Columvi’s Starglo regimen in April, and the National Comprehensive Cancer Network has added it to its treatment guidelines for certain second-line DLBCL patients, including its highest category 1 recommendation for patients who have relapsed late and are not candidates for transplants, Roche noted in a statement (PDF) Wednesday.
As Roche pointed out, Starglo is the first randomized phase 3 study in second-line transplant-ineligible DLBCL to show an overall survival improvement.
The FDA is expected to deliver a decision on Columvi’s second-line use by July 20, 2025.
As for Pfizer, the focus will likely be on the combination of Talzenna and Astellas-partnered Xtandi in first-line mCRPC who do not have homologous recombination repair (HRR) gene mutations.
The FDA in 2023 approved the cocktail in HRR-mutated patients, and Pfizer’s plan is to use a longer follow-up of the overall survival data to cover HRR-nonmutated tumors, for which PARP inhibitors like Talzenna have shown less efficacy.
A subgroup analysis of the phase 3 Talapro-2 trial linked Talzenna-Xtandi to a 12.6% reduction in the risk of death versus Xtandi alone among patients whose tumors were HRR-non-deficient or unknown.
On Darzalex, J&J’s target indication, smoldering myeloma, isn’t considered a cancer, but it can develop into myeloma.
In the phase 3 Aquila trial, patients who received Darzalex Faspro experienced a 51% lower risk of progression or death versus simple monitoring. The drug also had a higher rate of grade 3 or 4 treatment-emergent adverse events, at 40.4%, versus 30.1% for control.
During the review, the FDA will likely focus on the benefit-risk calculation of introducing an active drug in an early-stage condition where active monitoring is the standard practice, especially as Darzalex has proven highly effective in first-line multiple myeloma.
The industry will know more about the FDA’s intentions soon, as the agency is expected to publish its internal review reports two days before the ODAC meeting. In announcing the gathering, the FDA flagged that it was unable to publish its notice 15 days prior to the meeting due to “technical issues.”
The agency “concluded that there are exceptional circumstances that support holding this meeting without the customary 15-day public notice,” it said.
Industry watchers have been worried about potential delays at the FDA following recent mass layoffs at the agency. Although critical drug reviewers were spared from the downsizing, reductions affecting supporting roles have raised concerns of operational hiccups.
Further, there's an industry concern about possible drug policy changes under Makary. Alongside the job cuts, senior FDA leadership has undergone almost a complete makeover. Pazdur, who has been with the FDA for nearly three decades, has not publicly commented on the oncology office’s agenda since Makary ascended to the office in March.
In a short speech for accepting the 2025 AACR Enduring Impact Award for Transformative Service to Cancer Science and Medicine at the American Association for Cancer Research annual meeting on April 27, Pazdur recounted past advancements in cancer drugs and the dawn of the precision oncology era.
“I firmly believe that the next 25 years will bring even more transformative advances than the last,” he said.
Editor's Note: The story was updated to show that Richard Pazdur, M.D., represents the only FDA center director on the pharmaceuticals side left from the prior administration