The clock’s ticking on the potential arrival of the first China-made PD-1 inhibitor in the U.S.
Tuesday, Innovent Biologics and partner Eli Lilly said the FDA had accepted their application for Tyvyt, or sintilimab, in combination with Lilly’s own Alimta and platinum chemotherapy for newly diagnosed nonsquamous non-small cell lung cancer.
Chinese regulators already cleared the regimen in the indication back in February, and, now, the FDA’s set to hand out its decision by next March.
As the first PD-1 drug developed by a Chinese company to have a clear FDA path, Tyvyt’s regulatory experience and, perhaps more importantly, pricing strategy will have implications for existing players such as Merck & Co. and Bristol Myers Squibb as well as many other Chinese competitors to come.
Clinical data caveat
While the FDA didn’t call out any immediate review issues, the agency did state that it intends to convene an advisory committee meeting to discuss Tyvyt’s application. No details are available at this point, but the discussion will likely center on results from the phase 3 Orient-11 trial, which Lilly and Innovent are using as the cornerstone of the filing.
Lilly originally teamed with Innovent on Tyvyt specifically for the Chinese market, but the pharma company expanded the deal to cover global rights last year after seeing results from Orient-11.
The trial was conducted only in China, which poses the first challenge for an approval in the U.S. But Richard Pazdur, M.D., director of FDA’s Oncology Center of Excellence, has publicly said that the FDA would consider PD-1 applications based solely on clinical data from China. In fact, the FDA set an example by approving BeiGene’s BTK inhibitor Brukinsa in mantle cell lymphoma in 2019 based primarily on data from a pivotal study conducted in China.
Orient-11 has only reported data on the regimen’s ability to stall cancer progression, showing it could slash the risk of disease progression or death by 52% over chemotherapy.
However, as the king in front-line NSCLC, Merck’s Keytruda already has gold-standard life extension data in combo with Alimta and platinum chemo in front-line nonsquamous NSCLC. In the famous Keynote-189 trial, the Keytruda regimen slashed the risk of death by 51% over chemo at initial analysis, and the benefit stood strong at 44% at final analysis.
Still, Tyvyt’s progression-free survival data look very similar to the Keynote-189 findings at that trial’s interim analysis. Patients on the Keytruda regimen lived a median 8.8 months without progression, compared with 4.9 months for chemo. The Tyvyt regimen turned in a progression-free survival finding of 8.9 months at median versus five months for those on chemo.
With that, the discussion at the anticipated advisory committee meeting might touch upon whether progression-free survival data from Orient-11 are a good indicator of overall survival—and hence Tyvyt’s approvability—given existing experience in the PD-1 drug class.
Pricing as a potential lever
Still, if eventually approved, Tyvyt will have a tough time challenging Keytruda from an efficacy data angle. But pricing is a strategy the China-made PD-1 could leverage.
In a recent open letter to Libtayo maker Regeneron’s CEO Len Schleifer, M.D., Ph.D., Bernstein analyst Ronny Gal urged the company to lower the PD-1 latecomer’s price quickly before Chinese companies and their U.S. partners go down that path.
The FDA's Pazdur has noted that “there are no differences in price” among existing PD-1/L1s available in the U.S. The arrival of low-cost Chinese options “could potentially be a great thing for everyone because we haven’t seen the major Western pharmaceutical companies moving on price,” he said at an American Association for Cancer Research meeting in 2019, according to BioCentury.
Although the FDA doesn’t have jurisdiction over drug pricing, Pazdur’s comment at a minimum underscores the agency’s oncology drug reviewers have a welcoming attitude toward China-developed checkpoint inhibitors.
In his analysis in April, Gal figured “Lilly would reasonably use price in its positioning.” In direct discussions with the analyst, the Indianapolis pharma said in the U.S., “there would be segments of the market” where Tyvyt could effectively compete, Gal said. That’s about as explicit as a big pharma company would get to suggesting the use of cost as a lever in at least some segments, such as cost-sensitive U.S. payers, Gal figured.
Lilly and Innovent weren’t hesitant to play the price card to win market share in China. In 2019, the pair cut Tyvyt’s price by 64% to get the drug listed on the country’s national reimbursement program, making it the first in the PD-1/L1 class to secure that coverage.