Mixed outcomes for pharma in big week for FDA adcomms
This week, it was a case of mixed fortunes for pharma companies in FDA advisory committee meetings, as experts backed one cancer drug application from Johnson & Johnson but voted against three others from Roche, UroGen and Pfizer.
For J&J, there was a positive outcome as the Oncologic Drugs Advisory Committee (ODAC) voted six to two in favour of approval of its anti-CD38 antibody Darzalex Faspro (daratumumab/hyaluronidase) as a treatment for adults with high-risk smouldering multiple myeloma (HR-SMM).
The panel was assessing data from the phase 3 AQUILA trial of the drug, which showed a progression-free survival (PFS) rate of 63% and overall survival (OS) rate of 90% at five years, compared to around 41% and 87% in a comparator group who were simply monitored for progression. That data has also been published in the New England Journal of Medicine.
HR-SMM is a premalignant stage of the disease, usually with no symptoms, that is usually monitored every few months without any active treatment. If the FDA approves Darzalex Faspro for the indication, it will become the drug for the disease and could allow oncologists to "get in front of [the] cancer," according to J&J's head of oncology clinical research, Sen Zhuang.
It was a different story for Roche, as the ODAC considered data seeking to broaden the label for its CD20xCD3 bispecific antibody Columvi (glofitamab) in diffuse large B-cell lymphoma (DLBCL) and also convert an earlier accelerated approval to a full approval.
ODAC members voted eight to one against the filing to expand Columvi's use to include transplant-ineligible patients with relapsed or refractory DLBCL as a combination therapy with gemcitabine and oxaliplatin based on results from the STARGLO study, citing inconsistencies in the data and concerns with the patient cohort, which contained relatively few subjects from North America.
Columvi was approved by the FDA as a third-line or later therapy for DLBCL in 2023, but is vying to move up the treatment pathway and become a second-line option. Regulators in Europe have already approved the new indication based on STARGLO data showing that the Columvi regimen achieved a 41% reduction in the risk of death compared to Roche's anti-CD20 antibody MabThera/Rituxan (rituximab) plus chemo.
The ODAC also took a sceptical view of UroGen Pharma's application for UGN-102, an intravesical formulation of mitomycin, as a treatment for recurrent low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). Panellists voted five to four against approval on the grounds that the benefit/risk profile of the drug – which is intended to provide a minimally invasive treatment for the disease rather than surgery – had not been proven.
The filing was based primarily on findings from the single-arm phase 3 ENVISION trial, which showed an 80% complete response rate using URO-102 among patients with recurrent disease. Given the close vote, UroGen said it was still hopeful of a positive outcome from the FDA on its submission, which has an action date of 13th June.
Finally, Pfizer's attempt to expand the indications for its PARP inhibitor Talzenna (talazoparib) in prostate cancer was knocked back with a unanimous eight-to-nothing vote.
Already approved to treat adults with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) as a combination therapy with Pfizer's hormonal therapy Xtandi (enzalutamide), the company is hoping that data from the TALAPRO-2 trial will persuade the FDA to clear it for use in patients without the mutation.
The agency already rejected the application on one occasion, saying it was unconvinced by radiographic PFS data from the study, but Pfizer tried again after a late readout also handed an OS advantage to Talzenna plus Xtandi versus Xtandi and placebo. The panel was concerned by the design of the study, which failed to include a well-specified way to gauge efficacy in the HRR-negative patient population.
