Talazoparib Tosylate

In a resounding 8-0 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) rejected Pfizer’s combination of Talzenna and Xtandi for treating mCRPC patients without HRR mutations (non-HRRm). This decision deals a blow to one of Pfizer’s high-profile oncology strategies, despite notable improvements in survival outcomes reported in the TALAPRO-2 Phase III trial.   According to final data, the combination extended radiographic progression-free survival (rPFS) to 33.1 months compared to 19.5 months in the control group. Overall survival (OS) improved by nearly 9 months, reducing the risk of death by over 20%. Among HRRm-positive patients, rPFS nearly doubled, and OS was prolonged by 14 months. However, the core issue lay with non-HRRm patients, where regulators questioned whether the observed OS improvement was statistically credible or the result of confounding variables.   ODAC members raised concern that over a quarter of patients lacked confirmed HRR mutation status at randomization, and many of them were later found to be HRRm-positive. This undermined the reliability of the subgroup analysis. The FDA emphasized that biomarker-driven approvals must be rooted in prospective stratification, not retrospective data that might skew conclusions.   While Pfizer argued the mechanistic rationale was strong—citing synergy between PARP inhibition and androgen receptor blockade—and manageable safety signals, including anemia and absence of MDS/AML, the advisory panel stood firm. Regulators warned this could set a dangerous precedent by encouraging biomarker-independent use of PARP inhibitors, a direction unsupported by past trials with olaparib and rucaparib in similar settings.

Today, a brief rundown of news involving Pfizer and Sarepta Therapeutics, as well as updates from UroGen Pharma, Altos Labs and BioNTech that you may have missed.A Food and Drug Administration advisory panel on Wednesday voted unanimously against expanding use of Pfizers Talzenna in prostate cancer. All eight committee members concluded Pfizers data werent strong enough to support Talzennas benefits in metastatic prostate cancer patients who dont have a specific set of genetic alterations called homologous recombination repair mutations. Talzenna, a so-called PARP inhibitor, was approved for use alongside Xtandi in that particular group of prostate cancer patients in 2023. Pfizer has been hoping survival data accrued since then might convince the FDA to clear treatment in all people newly diagnosed with metastatic disease. Ben FidlerAgency panelists also declined to endorse a drug Urogen Pharma has been developing for a form of bladder cancer. Urogenis seeking clearance of the therapy, a formulation of the chemotherapy mitomycin, in a recurrent type of non-muscle invasive bladder cancer. But by a slim, 5-4 margin, FDA advisers determined the drugs benefits didnt outweigh the risks of treatment. UroGen shares fell by more than 50% following the vote. The FDA will issue a verdict by June 13. Ben FidlerHealth authorities in the U.K. are allowing Sarepta Therapeutics to continue dosing in a trial called Envision, which is testing the companys gene therapy Elevidys in people with Duchenne muscular dystrophy who either cant walk or who still can, but are older. In March, Sarepta revealed a boy who received Elevidysdied from acute liver failure, which led to a pause in testing in Europe. Writing in a Wednesday note to clients,Brian Skorney, an analyst at Baird, described the decision by U.K. regulators as a favorable signal for how the Food and Drug Administration and the European Medicines Agency may view Elevidys. Ned PagliaruloBioNTech will invest up to 1 billion, or about $1.34 billion, in drug research in the U.K. over the next decade, the company said Tuesday. Alongside that commitment, BioNTech will receive as much as 129 million in grant funding from the U.K. government over 10 years, one of the largest grants the country has handed to a pharmaceutical company. That money will help BioNTech establish two new R&D centers, one of which will be based in Cambridge, England and focus on genomics, oncology and other research priorities. BioNTech will build a U.K. headquarters in London as well. Ben FidlerAltos Labs, a buzzy startup backed by billions of dollars in venture investment, has put some of its funds to use buying Dorian Therapeutics, a small privately held company based in San Carlos, California. In a LinkedIn post, Dorian CEO Maddalena Adorno wrote that Dorians cellular rejuvenation research will continue at Altos, which is studying the basis of aging and how that translates to disease. Dorians research started at the Stanford University School of Medicine years ago,Adorno wrote. Ned Pagliarulo '