With its latest trial win, Eli Lilly and its Chinese partner Innovent Biologics are eyeing an all-important front-line non-small cell lung cancer approval in China for their PD-1 checkpoint inhibitor, Tyvyt. But competition with Merck & Co.’s formidable Keytruda lies ahead.
Adding Tyvyt (sintilimab) to Lilly’s Alimta and platinum chemo significantly extended the time to tumor progression or death in previously untreated nonsquamous NSCLC patients without EGFR or ALK mutations, the new data show. Presented at the International Association for the Study of Lung Cancer virtual presidential event Satuday, the results came from a phase 3 trial in China dubbed Orient-11.
Tyvyt's progression-free survival performance in Orient-11 was quite similar to Keytruda’s in the global phase 3 Keynote-189 trial, which earned Merck's PD-1 king its conditional first-line chemo combo nod in China last April and its full go-ahead in the U.S.
In the 397-patient Orient-11 study, patients who got the Tyvyt-chemo cocktail lived a median 8.9 months without their tumors progressing, versus 5.0 months in the chemo group. In comparison, in the 616-patient Keynote-189 study, the median PFS came in at 8.8 months for the Keytruda combo, versus 4.9 months for chemo.
What sets the two drugs apart could lie in the overall survival data, the gold standard when evaluating cancer drugs. Tyvyt only reported a “nominally significant” improvement in patients' lifespan.
Keytruda, on the other hand, is famous for its monster 51% reduction in the risk of death in Keynote-189. Even in a long-term follow-up, the overall survival benefit of the Keytruda-chemo pairing stood strong at 44%.
Innovent and Lilly’s application for Tyvyt in first-line nonsquamous NSCLC was accepted for review by Chinese authorities in April.
Lilly earned Chinese rights to Tyvyt through a pact the two signed in 2015, and the drug was first approved in December 2018 in third-line classic Hodgkin lymphoma. Starting from this year, Tyvyt officially became the first—and only—PD-1/L1 agent included in China’s National Reimbursement Drug List after a 64% price cut.
Industry watchers at that time argued that if such a steep discount could be offered for such a small indication as cHL, the price could be further lowered after the large NSCLC war begins.
Pricing is a key advantage Tyvyt—as well as other PD-1/L1 inhibitors home-grown in China—has over Keytruda. Without national reimbursement, and for patients eligible for assistance, the annual cost for Tyvyt, at roughly CNY 102,300 ($14,680), is nearly a third that of Keytruda’s CNY 286,600 ($41,132), according to data compiled by GBI Health. The national reimbursed price of Tyvyt almost matches that after patient assistance.
“Besides benefiting cHL patients, the listing provides a boost to [Tyvyt’s] general accessibility in hospital pharmacies over rivals,” GBI wrote in a recent report.
In the first half of 2020, Innovent reported Tyvyt sales of CNY 331.6 million ($47.6 million). In fact, Tyvyt was the biggest driver of Lilly’s 50% scripts volume growth in China last quarter, thanks to its addition to national coverage, Lilly CFO Joshua Smiley told investors on a conference call last week.
Keytruda isn’t Tyvyt’s only competitor, though. In April, local biotech major BeiGene said its former Celgene-partnered PD-1, tislelizumab, also hit the primary goal of progression-free survival in its own Alimta-platinum chemo cocktail in first-line treatment of nonsquamous NSCLC.
BeiGene's application for that indication was accepted by Chinese regulators in June. Tislelizumab was officially launched in third-line cHL in China in March at an estimated annual cost of CNY 106,900 ($15,340), according to GBI data.
The three meds were also up for a fight in first-line squamous NSCLC. In November, Keytruda nabbed its chemo combo squamous go-ahead in China based on data from the phase 3 Keynote-407 trial. Both BeiGene and Innovent have said their PD-1-chemo combo have hit trial goals in their respective phase 3s. About 70% of NSCLC cases in China are the nonsquamous subtype, according to Lilly.
Lilly only holds a stake in Tyvyt, a monoclonal antibody, within China. But through an expanded collaboration unveiled in October 2015, the company has ex-China rights to up to three anti-PD-1-based bispecific antibodies developed by Innovent.