After TIGIT divorce, Novartis returns tislelizumab to BeiGene as PD-1 gains first European nod

Novartis has ended its major cancer immunotherapy collaboration with BeiGene more than two years after touting the benefits of having a PD-1 inhibitor.

BeiGene has regained full rights from Novartis for the PD-1 inhibitor tislelizumab, BeiGene said in a press release Tuesday. The Swiss pharma previously had co-development and co-commercialization rights to the drug in North America, Japan, the EU and several other countries under a $650 million upfront licensing deal signed in early 2021.

The news marks the end of a second immuno-oncology partnership between the two companies after they parted ways on BeiGene’s anti-TIGIT candidate ociperlimab about two months ago.

In a statement to Fierce Pharma, Novartis said a changing PD-1 inhibitor landscape led to the decision to terminate the tislelizumab agreement.

“This decision will provide Novartis with greater flexibility for development of its unique, potentially transformational pipeline assets, notably in markets where there are already approved PD-1 therapies in desired indications that can support development of our novel IO combination programs.”

Without a Big Pharma partner, BeiGene will face a lot of pressure entering the complicated and crowded PD-1/L1 space, in which eight other drugs are already approved across various tumor types in the U.S.

During an interview with Fierce Pharma, Josh Neiman, BeiGene’s chief commercial officer for North America and Europe, didn’t articulate whether BeiGene will look for a new partner, saying that “it’s always hard to predict all of the future with certainty.”

This is also the second time BeiGene regained tislelizumab from a foreign pharma. Back in 2019, Celgene returned the drug in the middle of its $74 billion merger with Bristol Myers Squibb because of conflict of interest with BMS’ Opdivo.

Also Tuesday, BeiGene said the European Commission has doled out its first approval for tislelizumab, to be sold under the brand Tevimbra. The indication is previously treated esophageal squamous cell carcinoma, the same one that’s suffering from a significant delay with the FDA.

With uncertainty hanging over the FDA’s review timeline for Tevimbra in the second line, BeiGene has filed a new biologics license application for first-line use. Tuesday, the company said the FDA had accepted the submission with a target decision date in the second half of next year. 

Neiman declined to comment on Tevimbra’s specific price in Europe but noted that BeiGene now has full control over pricing, while it was Novartis’ decision before. Typically, a drugmaker need to negotiate reimbursement with each European market.

“Consistent with BeiGene’s overall philosophy, bringing innovative medicines to patients with a focus on not only providing the medicine but doing it in a way that broadens accessibility and affordability, we will certainly take that approach with tislelizumab,” Neiman said.

The shift means that BeiGene will inevitably need to expand its commercial team, Neiman said. The company currently sells blood cancer drug Brukinsa in the U.S. But BeiGene has said in the past that hematology is more concentrated compared with solid tumors, which require larger commercialization forces.

Pointing to how BeiGene built its commercial team around Brukinsa first in smaller indications, Neiman said “there’s a really clear path for us to be able to build out [tislelizumab’s] team in a way that really meets the scale of our initial indications, and then expand that thoughtfully over time.”

As for the pipeline, there will be no changes to ongoing tislelizumab clinical trials on BeiGene’s part because of the termination, Mark Lanasa, M.D., Ph.D., BeiGene’s chief medical officer for solid tumors, told Fierce Pharma. These include a phase 3 trial that pairs tislelizumab with ociperlimab and chemotherapy in first-line metastatic non-small cell lung cancer (NSCLC) as well as a midstage study with a LAG-3 agent in colorectal cancer.

Under the original alliance, each party had freedom to develop tislelizumab with their own assets. For BeiGene, combinations with the PD-1 inhibitor “remain high priority,” Lanasa said.

Novartis has communicated that it wants to continue to use tislelizumab for some of its clinical trials, the BeiGene exec added.

“Ongoing studies may continue under the current sponsors. Tislelizumab will be made available to Novartis for this purpose,” a Novartis spokesperson said in a separate statement.

When asked about whether Novartis still plans to have an in-house PD-1, the spokesperson said the company “will not speculate on future pipeline decisions at this time.”

In addition to those clinical trials, Novartis has also agreed to continue to manufacture tislelizumab as a contractor.

Tislelizumab has had a rough patch since Novartis signed on. In early 2022, the FDA rejected Eli Lilly and Innovent Biologics’ PD-1 inhibitor Tyvyt (sintilimab) in NSCLC over China-only data and an inferior comparator arm. It marked a change of course as the FDA’s oncology department had previously welcomed data from China to support regulatory reviews.

This turn of events forced Novartis to rethink its regulatory plans given tislelizumab also has multiple China-only or predominantly China trials. Last summer, Novartis disclosed that it wouldn’t seek a monotherapy filing for tislelizumab monotherapy in newly diagnosed NSCLC in the U.S. after receiving feedback from the FDA.

Also last year, tislelizumab as a single agent matched up to Bayer’s aging Nexavar in front-line liver cancer. BeiGene has talked to the FDA about that study, Lanasa said, but, “based upon the regulation, having noninferiority rather than superiority makes it a tough discussion with the FDA.”