FDA Scrutinizes Approval Bids from J&J, Pfizer, and Roche Ahead of Oncology Advisory Committee Meeting

The upcoming two-day oncology advisory committee meeting organized by the FDA, scheduled for May 20 and 21, 2025, will mark the first such meeting during Dr. Marty Makary’s tenure as FDA Commissioner. This meeting is poised to bring key discussions around the approval pathways for several cancer drugs, with a sharp focus on data integrity and patient population selections presented by the pharmaceutical giants Johnson & Johnson (J&J), Pfizer, and Roche.

Johnson & Johnson’s Challenge with Darzalex Faspro

At the forefront of the discussion is J&J’s bid to introduce Darzalex Faspro for high-risk smoldering multiple myeloma (SMM). The FDA has raised concerns regarding the patient pool used in J&J’s phase 3 Aquila trial, stating that participants do not conform to the contemporary definition of “high-risk.” The agency is particularly interested in whether the study’s findings are applicable to real-world high-risk patients, given that recent guidelines suggest only 41% of trial participants would qualify as high-risk under the updated criteria.

Moreover, the FDA has indicated that for an asymptomatic precursor condition like SMM, more comprehensive survival data may be essential to accurately establish the drug’s benefit-risk profile. This hesitance to approve arises partly from the trial’s inability to demonstrate a statistically significant improvement in overall survival, which is deemed crucial for efficacy assessment. Despite J&J’s arguments in favor of early intervention, the FDA remains cautious regarding the potential implications of initiating treatment before a full-blown multiple myeloma diagnosis.

Pfizer’s Talzenna: Concerns Over Trial Design

Meanwhile, Pfizer is striving to expand the use of its PARP inhibitor Talzenna as a first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) in patients devoid of homologous recombination repair (HRR) gene mutations. However, the FDA has voiced reservations regarding the Talapro-2 trial design, criticizing it as “suboptimal.” The primary concern lies in the failure to pre-specify an analysis for the sizable HRR-negative subgroup, which constitutes a significant portion of mCRPC patients.

The lack of statistically powered testing raises concerns over the study’s ability to accurately depict outcomes for HRR-negative patients, posing a risk of drawing misleading conclusions. Furthermore, the exploratory analyses present an unclear benefit regarding overall survival, further deepening the uncertainty around approval.

Roche’s Application for Columvi: Divergent Outcomes

Roche’s application for its combination therapy, incorporating Columvi for patients with previously treated diffuse large B-cell lymphoma (DLBCL) who are not candidates for stem cell transplant, faces scrutiny as well. The FDA’s analysis of the phase 3 Starglo trial uncovered notable discrepancies in survival outcomes based on geographic patient distribution. While the overall results indicated a substantial improvement in overall survival globally, subgroup analysis has shown contrasting results for the U.S. and Europe, suggesting a mere 6% increased mortality risk compared to control.

Considering that the trial enrolled a significant number of participants from Asia, these geographic variances in outcomes warrant close examination, as they may reflect the efficacies of alternative therapies available in specific regions, such as CAR-T therapies in the U.S. and Europe, which could influence patient survival rates.

UroGen and Jelmyto’s Submission

In addition to the applications from the Big Pharma trio, the FDA is also considering UroGen‘s submission for Jelmyto, an intravesical solution addressing recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. The FDA seeks opinions on whether durable complete response data obtained in a single-arm trial is sufficient to demonstrate the drug’s efficacy, particularly in a context where no approved treatments exist.

Conclusion: A Defining Moment for Oncology Drug Approval

The deliberations at the upcoming advisory committee meeting are poised to reveal the FDA’s stance towards emerging cancer therapies amidst evolving clinical data standards and patient selection criteria. The scrutiny applied to J&J, Pfizer, and Roche’s trials indicates a rigorous approach to ensuring that any approved treatments genuinely deliver clinical value to patients.

As these Big Pharma entities navigate the FDA’s concerns, the industry watchers are poised for a potentially transformative meeting that could set the tone for future oncology drug approvals under the new FDA leadership of Dr. Makary. It remains pivotal for these companies to address the documented concerns comprehensively to secure approval and offer meaningful solutions to patients battling various forms of cancer.