Rejection, withdrawal, delay: New PD-1 cancer immunotherapies have had a hard time reaching the U.S. lately. For Novartis and BeiGene’s China-approved contender, the roadblock results from COVID-related travel restrictions.
The FDA has delayed a decision for the companies’ tislelizumab in previously treated esophageal squamous cell carcinoma (ESCC), BeiGene said Thursday. The companies were quick to point out that the FDA only cited COVID-related travel restrictions that had stopped the agency from performing inspections in China.
“Our understanding based on the FDA guidance is that typically when a deferral is issued, there are no other issues with the data in the application package at that time,” a BeiGene spokesperson told Fierce Pharma.
A deferral isn’t a rejection, and the FDA has in the past issued complete response letters when it couldn’t conduct on-site inspections.
The decision was originally expected Tuesday, and the FDA hasn’t provided a new anticipated decision date, BeiGene said.
“The FDA stated that they are monitoring the public health situation and travel restrictions and actively working to schedule outstanding inspections,” the spokesperson said.
BeiGene recently started commercial manufacturing of tislelizumab for the Chinese market at its new biologics facility in Guangzhou. It also has a tislelizumab supply contract with Boehringer Ingelheim.
Meanwhile, BeiGene recently began building a large, 42-acre biologics manufacturing and R&D site in New Jersey to help produce tislelizumab for the U.S. market, but completion of the first phase isn’t expected until mid-2023.
Tislelizumab is the latest China-developed PD-1 to hit a setback in its bid to reach the U.S. In a high-profile rejection earlier this year, the FDA blasted Eli Lilly and Innovent Biologics’ Tyvyt (sintilimab) for using single-country pivotal trial that included an outdated comparator therapy for an application in newly diagnosed non-squamous non-small cell lung cancer.
Then in April, Coherus BioSciences and Junshi Biosciences’ toripalimab got its own FDA rebuff in nasopharyngeal carcinoma. After completing quality process changes requested by the FDA, the two companies have refiled the drug and last week received a new target action date for late December. But the companies warned that COVID travel constraints might trip up that timeline, noting that onsite inspections in China would be required.
Given those two recent rejections, “the decision to delay the application versus issuing a CRL and terminating the review cycle could be viewed as a positive,” SVB Securities analysts said about tislelizumab in a Thursday note.
It’s not just China-developed PD-1s that are facing challenges with the FDA. Agenus in October withdrew balstilimab in cervical cancer after a full go-ahead for Merck’s PD-1 king Keytruda effectively closed the accelerated approval pathway for that indication. Before that, the FDA had denied Incyte and MacroGenics’ retifanlimab in anal cancer, demanding more data.
For tislelizumab, Novartis in-licensed the China-approved PD-1 in 2021 with $650 million upfront as its own med failed to impress in clinical trials. The company plans to make tislelizumab the backbone for potential combinations with Novartis’ internal pipeline.
If eventually approved, tislelizumab would enter a highly saturated market of PD-1/L1 inhibitors, including in ESCC. During a recent interview with Fierce Biotech, BeiGene’s R&D chief, Lai Wang, Ph.D., acknowledged that the current second-line ESCC indication is a small one.
On top of that, Novartis has stated an intention to pursue additional indications in second-line non-small cell lung cancer and possibly nasopharyngeal carcinoma later this year. The pair has also reported positive pivotal trial results in frontline ESCC and newly diagnosed stomach cancer that could support potential filings.
“We were discussing with Novartis about next regulatory interactions as well as filing plans,” Lai said at the time.