REGN-5678

Dive Brief:Regeneron Pharmaceuticals said the Food and Drug Administration could approve a much-anticipated new version of its top-selling eye drug during the third quarter, a quicker-than-expected turnaround after the regulator rejected the therapy in June.The FDA turned back a high-dose form of Eylea over inspection findings at a Catalent facility that fills vials of the drug. In an earnings call Thursday, CEO Leonard Schleifer said required manufacturing data will be submitted by mid-August, and the agency plans to work expeditiously to complete a review before Aug. 20. The evaluation could also be extended if its not finished by then.The news caused Regeneron shares to climb and recoup some of the value they lost after news of the FDA rejection. But the stock price gains also helped mask some setbacks to Regenerons development pipeline, wrote RBC Capital Markets analyst Brian Abrahams.Dive Insight:When the FDA surprised Wall Street and rejected Regenerons application for high-dose Eylea, analysts expected the worst.At the time, some said that companies in similar situations faced delays as long as nine months something Regeneron could ill afford with biosimilar competitors looming and a new Roche drug, Vabysmo, grabbing market share from its long-dominant medicine.Regenerons announcement Thursday provided what RBCs Abrahams called much-needed partial clarity on the path forward for high-dose Eylea. Its still unclear exactly when the FDA might make a decision, as another manufacturing inspection may be necessary. But the potential worst case scenario of [a] long delay is less likely, he wrote.That news was delivered alongside quarterly sales of $1.5 billion for Eylea, which beat analyst expectations. The drug, which still accounts for the bulk of Regenerons revenue, delivered despite Roches commentary around Vabysmos share gains, added Piper Sandler analyst Christopher Raymond. Roches drug generated more than $1 billion in the first half of the year.Rumors of Eyleas demise have been greatly exaggerated, Raymond wrote.Yet Regeneron stumbled elsewhere. The FDA is requiring a second, positive Phase 3 result before the company can seek approval of its inflammatory disease drug Dupixent in a common lung disease, which is seen as a multibillion-dollar market opportunity. Regeneron previously discussed the possibility of an early approval in the condition, known as COPD, but will now have to wait for study results expected next year.Regeneron also reported a setback in its cancer drug portfolio. A second patient died in a study testing a prostate cancer medicine that has shown promise in early testing. Regeneron is changing its development plan for that drug, named REGN-5678, as a result.The company has several other prospects in development, among them the blood cancer drug odronextamab and linvoseltimab and the melanoma treatment fianlimab. Its also exploring a variety of drug combinations meant to help the company stand out from its peers.Still, Regeneron is behind competitors with similar drugs, and analysts have been skeptical as to whether it can succeed. It will take time and developmental nuance for these efforts ... to play out, Abrahams wrote. '

Regeneron's revised R&D road map includes the study of the bispecific as a monotherapy. Regeneron is rethinking development of its prostate cancer bispecific after two patients died in a clinical trial. The deaths prompted the Big Biotech to stop enrolling patients to receive REGN5678 and a full dose of its checkpoint inhibitor, but a reshaped bispecific development program is continuing.  REGN5678 is designed to bind to CD28 on cytotoxic T-lymphocytes (CTLs) and PSMA on tumor cells. By binding to the costimulatory T-cell-specific surface glycoprotein and tumor-associated antigen, the drug candidate could activate CTLs and direct them to attack cancer cells. Regeneron identified the targeting of CD28 on previously activated T cells as a way to reduce toxicity compared to CD3 bispecifics.  The candidate, which may synergize with anti-PD-1/L1 checkpoint inhibitors, came through the release of preliminary phase 1/2 data unscathed. But safety concerns have since come to light and prompted a shift in the R&D strategy. In its second-quarter results statement, Regeneron reported two immune-mediated deaths in a cohort of patients who received REGN5678 in combination with Libtayo, the company’s checkpoint inhibitor. The deaths drove Regeneron to stop enrolling patients to receive REGN5678 and a full dose of Libtayo. Regeneron is sticking with the candidate, though. The revised R&D road map includes the study of the bispecific as a monotherapy and in combination with lower doses of Libtayo and other immunotherapy modalities. Regeneron’s other costimulatory bispecific development programs, which include candidates against EGFR, MUC16 and CD22, are unaffected and are still making their way through dose escalation.  Even so, the removal of the option to pair REGN5678 with a full dose of Libtayo is a blow. Regeneron took the bispecific into the clinic in the belief the combination may be able to overcome the resistance of metastatic castration-resistant prostate cancer to PD-1 inhibition. Overcoming resistance could bring the benefits of checkpoint inhibitors to prostate cancer, a setting in which the drugs have had little impact. CD28 has a troubled history as a cancer target. The CD28 superagonist TGN1412 caused critical illnesses linked to cytokine storms in a phase 1 clinical trial in 2006. In recent years, companies including Johnson & Johnson and Sanofi have invested in candidates against the target, but fresh concerns emerged last year, when two deaths stopped trials of Alpine Immune Sciences’ conditional costimulator of CD28.