FDA Scrutinizes Cancer Drug Approval Bids from J&J, Pfizer, and Roche

In a pivotal moment for oncology drug development, the FDA’s Oncology Advisory Committee is set to convene on May 20 and 21, marking the first such meeting under new FDA Commissioner Marty Makary, M.D.. At the forefront of this meeting will be the consideration of approval bids from major pharmaceutical companies Johnson & Johnson (J&J), Pfizer, and Roche. A deep dive into the submitted clinical data is expected, especially as the agency raises significant questions regarding patient selection criteria and the effectiveness of the proposed treatments.

Johnson & Johnson: Seeking Approval for Darzalex Faspro

J&J is seeking to expand the indications for its drug Darzalex Faspro into the realm of high-risk smoldering multiple myeloma (SMM). However, the FDA has raised concerns about patient eligibility in J&J’s Phase 3 Aquila trial. Specifically, only 41% of participants were characterized as “high-risk” based on updated stratification guidelines. The FDA questions whether the trial’s findings can truly represent the current high-risk patient population.

One of the core issues noted by the FDA is that SMM is typically asymptomatic, and current medical guidelines recommend monitoring instead of immediate treatment. The FDA has expressed reservations regarding the implications of early treatment, suggesting that more mature survival data might be necessary to accurately assess the benefit-risk profile of the therapy. Although the Aquila trial met its primary endpoint for progression-free survival, it lacked the necessary power to demonstrate a statistically significant overall survival benefit, with only a 5% absolute survival difference reported at five years between treatment arms.

Pfizer: Challenges with the Talapro-2 Trial

Pfizer’s submission focuses on expanding the use of its PARP inhibitor Talzenna for initial treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the FDA has criticized the trial design, particularly in its handling of the biomarker-negative population. The Talapro-2 trial did not adequately define a formal analysis for patients without homologous recombination repair (HRR) gene mutations, creating a potential for misleading interpretations in this significant subgroup. The FDA has pointed to an exploratory subgroup analysis which found only a 12% reduction in death risk for these patients.

Further complicating matters, the FDA highlighted that the study was primarily designed to analyze HRR-mutated patients, casting doubt on whether the data can be extrapolated to all mCRPC patients. The agency expressed skepticism given previous trials for other PARP inhibitors have not demonstrated benefits for HRR-negative patients. Pfizer argues that its combination treatment with Xtandi might yield different efficacy compared to other combinations that utilize Zytiga.

Roche: Data Discrepancy in DLBCL Treatment

Roche faces scrutiny regarding its application for a combination therapy involving Columvi for patients with previously treated diffuse large B-cell lymphoma (DLBCL). The FDA has expressed concerns about the geographical representation in the Phase 3 Starglo trial, where approximately 50% of patients were enrolled outside the U.S. and Europe. The trial demonstrated a 38% improvement in overall survival; however, subgroup analyses revealed concerning trends, particularly among non-Asian patients, where a higher risk of death was noted.

The FDA’s review found a stark difference in survival outcomes, indicating a 61% reduction in death risk among patients from Asian countries, contrasting with an adverse outcome trend in North America and Europe. Roche contends that access to effective CAR-T therapies, which are typically available only at specialized centers, may explain these discrepancies in survival rates. The company argues for the continued necessity of its treatment in a context where high-access therapies are not universally available.

UroGen: Additional Considerations

Besides the three pharma giants, UroGen is proposing its intravesical chemotherapy solution Jelmyto for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. As no therapies currently exist in this niche, the FDA is seeking input on whether data from a single-arm trial demonstrating durable complete response can suffice for regulatory approval.

Conclusion: A Majestic Intersection of Innovation and Scrutiny

The upcoming FDA advisory committee meeting sheds light on the scrutiny facing novel oncology therapies as they strive for market approval amid rigorous evidence standards. The questions raised reflect transparency and an ongoing commitment to ensuring that treatment candidates meet modern safety and efficacy benchmarks. As stakeholders await the committee’s deliberations, these developments highlight the vital intersection between innovative drug development and the regulatory landscape that governs it. Investors should keep a close eye on these proceedings, as outcomes may substantially impact the stock performance of J&J, Pfizer, and Roche moving forward.