Novartis, Coherus PD-1 drugs finally set for FDA manufacturing inspections after COVID delays

After months of COVID-related delays, the FDA’s reviews of two China-made PD-1 cancer immunotherapies are finally moving forward.

The FDA has scheduled a manufacturing inspection for Novartis and BeiGene’s tislelizumab in the second quarter, a Novartis spokesperson told Fierce Pharma. Meanwhile, the pair is still awaiting confirmation of timing for a clinical site inspection, which is also required for an approval, the spokesperson added.

Separately, Coherus BioSciences reported earlier this month that the FDA will conduct a manufacturing inspection for its Junshi Biosciences-partnered toripalimab in the second quarter.

The planned preapproval inspections offer a clearer timeline of the FDA’s regulatory plan for the two PD-1 latecomers, which aim to crack into a multibillion-dollar market years after their approvals in China. Previously, the reviews of tislelizumab and toripalimab were put on hold because FDA staffers couldn’t travel to China to perform required inspections.

In tislelizumab’s case, Novartis and BeiGene are seeking an approval in previously treated esophageal squamous cell carcinoma. BeiGene has proposed to produce the drug initially from a Boehringer Ingelheim site in China. In 2021, Novartis in-licensed the drug from BeiGene for $650 million upfront plus royalties and milestones.

Originally, the FDA was expected to deliver a verdict on the tislelizumab application by July 12, 2022. But, when that day came, BeiGene said the agency couldn’t make a decision because of COVID-related travel restrictions. As tislelizumab languished in regulatory limbo, Bristol Myers Squibb in May 2022 followed Merck into newly diagnosed esophageal cancer with a pair of FDA approvals for Opdivo combinations with chemotherapy or Yervoy.

As for toripalimab, Coherus and Junshi are angling for a niche U.S. indication at first. They're hoping to make their medicine the first PD-1 approved in recurrent or metastatic nasopharyngeal carcinoma, a rare type of head and neck cancer.

But the FDA in May 2022 rejected toripalimab’s application, asking the company to make a quality process adjustment. At that time, the FDA also flagged the pandemic-related lockdown in China as a potential problem for any resubmission.

After Coherus and Junshi quickly made the change and resubmitted their application, the agency set Dec. 23, 2022, as its new target action date. The review was then stalled again because FDA staffers couldn’t inspect the manufacturing facility by that time.

Given the drugs’ protracted review timelines and the lack of a complete response letter in either application, the FDA has likely already reviewed all relevant data and is only waiting on the outcome of the inspections as the final piece in its reviews.

Both drugs are vying to become the first China-made PD-1 inhibitor to be available in the U.S., a goal Eli Lilly failed to accomplish in its former collaboration with Innovent Biologics. 

The FDA rejected Innovent’s Tyvyt a year ago over China-only clinical trial data. The decision sent shock waves across all Chinese PD-1/L1 players and their U.S. partners. Novartis, for example, scrapped U.S. filing plans for some indications, including for tislelizumab monotherapy in non-small cell lung cancer and another one for front-line nasopharyngeal cancer.

Now, Novartis is also planning additional filings for tislelizumab in front-line esophageal cancer and stomach cancer.

For its part, Coherus has recently worked with Junshi to adjust its toripalimab development plan based on the FDA’s position on multiregional clinical trials, Theresa LaVallee, Coherus’ chief development officer, said during the company’s fourth-quarter earnings call earlier this month.

Besides the clinical trial supporting the current nasopharyngeal cancer application, Coherus is focusing on a small solid tumor study currently underway in the U.S., she said.

In addition, both Novartis and Coherus are working with their partners to explore their PD-1s’ combinations with investigational TIGIT inhibitors.

Meanwhile, with a Wednesday approval for Incyte’s Zynyz, the FDA has greenlighted altogether eight PD-1/L1 antibodies for various cancer types.