The FDA is tightening its act around checkpoint inhibitor approvals. But to hear Novartis Oncology president Susanne Schaffert tell it, the company’s BeiGene-partnered PD-1 inhibitor tislelizumab has a differentiated profile that could meet FDA’s high demand.
In the past, BeiGene has had a robust proportion of clinical trials patients enrolled outside China, which gives Novartis confidence in a decent population representing U.S. patients, Schaffert said during an interview on the virtual sidelines of the J.P. Morgan Healthcare Conference.
The partners already have tislelizumab’s first U.S. application in esophageal squamous cell carcinoma under FDA review, with a decision expected by July 12. The phase 3 trial used to support the filing, dubbed Rationale 302, included multiple sites in the U.S.
Wrinkles appeared in the FDA path for China-developed PD-1/L1 drugs after Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence, blasted repetitive PD-1/L1 development activities in a recent opinion piece published in the New England Journal of Medicine.
As part of what Pazdur called a clinical development “Wild West,” the FDA official singled out China-made PD-1/L1s, noting that some of the sponsors are using China-only—or predominantly China—data from trials duplicating those by existing drugs to seek U.S. approvals. If the drugs were developed in the U.S. for an approved indication, they would have had to run head-to-head noninferiority studies with an approved PD-1/L1 therapy.
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“Trials conducted outside the United States must address the additional regulatory hurdle of demonstrating their results’ generalizability to the U.S. population,” Pazdur and a colleague wrote in the article.
That could pose a problem for the second U.S. indication Novartis and BeiGene are pursuing for tislelizumab: previously treated non-small-cell lung cancer. There, BeiGene has life extension data over chemotherapy from the phase 3 Rationale 303 trial, which, although a global study, doesn’t include any U.S. sites.
Still, Schaffert said she’s confident that the companies will find a good regulatory path with the FDA in NSCLC.
From here on, all the new development programs that Novartis is running with tislelizumab alongside novel Novartis assets will all be “truly global trials,” Schaffert said. “The idea is to leverage Novartis’ network on clinical trial sites worldwide—we can make sure the FDA requirements are considered and respected.”
These include combinations of tislelizumab with BeiGene’s investigational anti-TIGIT antibody ociperlimab, which Novartis just signed on for $300 million upfront plus a $700 million option exercise fee to be paid before late 2023.
BeiGene currently has two phase 2 trials of the TIGIT drug expected to read out later this year. Before making a full commitment to the drug, Novartis wants to see “a clear benefit” of the PD-1/TIGIT combo over PD-1 alone in terms of better response rate, efficacy and effect durability, Schaffert said.
An FDA decision for tislelizumab and potential option-in of ociperlimab are just two of several important milestones for Novartis’ oncology department in 2022. The Swiss pharma could also see results from two postsurgery studies in early cancers that carry billion-dollar implications: canakinumab—sold as Ilaris in inflammatory diseases—in NSCLC and Kisqali in HR-positive, HER2-negative breast cancer.
Neither of those indications are going to be easy wins for Novartis. The company has kept canakinumab’s hope in the so-called adjuvant setting alive despite two failures in metastatic disease. As for Kisqali, Eli Lilly’s rival drug Verzenio recently became the first CDK4/6 inhibitor to be approved in adjuvant breast cancer, though Novartis is targeting a broader patient population.
Moreover, radioligand therapy 177Lu-PSMA-617 is currently under FDA priority review in pretreated metastatic castration-resistant prostate cancer.