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

The U.S. Food and Drug Administration (FDA) is raising questions about the clinical data provided by Johnson & Johnson, Pfizer, and Roche for their respective cancer drugs ahead of an upcoming oncology advisory committee meeting. The agency's concerns primarily revolve around patient selection and data applicability, potentially creating hurdles for the pharmaceutical giants in their pursuit of new indications or expanded use of existing treatments.

J&J's Darzalex Faspro for Smoldering Multiple Myeloma

The FDA is questioning whether patients enrolled in J&J's phase 3 Aquila trial for Darzalex Faspro in high-risk smoldering multiple myeloma (SMM) match the current definition of "high-risk." Only 41% of participants in the study are categorized as high-risk according to new standards, prompting concerns about the applicability of the findings to real-world populations.

J&J argues that while risk stratification criteria have evolved since the trial's design in 2015, the risk of progression to multiple myeloma appears consistent across risk models. The company maintains that high-risk SMM patients can benefit from proactive therapy, especially given the lack of approved treatments in this setting.

The FDA also raised concerns about the implications of early treatment in asymptomatic SMM patients and whether more mature overall survival data are needed to determine the drug's benefit-risk profile.

Pfizer's Talzenna Expansion Bid

Pfizer is seeking to expand the use of its PARP inhibitor Talzenna in combination with Xtandi for first-line treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients without homologous recombination repair (HRR) gene mutations. The FDA noted that Pfizer's Talapro-2 trial did not define a prespecified formal analysis for the HRR-negative patient population, which represents the majority of mCRPC patients.

The agency criticized the study's "suboptimal design," highlighting the lack of a statistically powered test in the biomarker-negative population. An exploratory subgroup analysis found only a 12% death-risk reduction for patients with HRR-negative or unknown tumors, with survival curves crossing and overlapping multiple times.

Pfizer contends that preclinical models suggest Xtandi might better synergize with PARP inhibition compared to other combination therapies that have not demonstrated benefits in this patient subgroup.

Roche's Columvi Combination for DLBCL

Roche's application for a combination incorporating Columvi in previously treated diffuse large B-cell lymphoma (DLBCL) patients who are not candidates for stem cell transplant is facing scrutiny due to geographical disparities in trial results. The FDA voiced concerns about the representation of U.S. patients in the phase 3 Starglo trial and noted that the study's positive readout appeared to be entirely driven by patients outside the U.S. and Europe.

Prespecified subgroup analyses revealed potential unfavorable survival outcomes in white patients and those enrolled in Europe or North America. The FDA found a marked difference between Asian and non-Asian regions, with the Roche regimen cutting the risk of death by 61% in Asian countries but showing a 6% higher risk of death in the non-Asian group.

Roche argues that despite the availability of CAR-T therapies in the U.S. and Europe, there remains a significant unmet need for immediately available, effective treatment options to rapidly control this aggressive disease.