ArriVent shares lose about half their value after lung cancer drug misses Phase 3 goal

ArriVent BioPharma said Tuesday that its lead drug, firmonertinib, failed to significantly delay the worsening of a rare type of lung cancer in a Phase 3 trial, and its shares lost about half their value.

The trial, called FURVENT, enrolled 398 previously untreated patients with advanced non-small cell lung cancer whose tumors carry EGFR exon 20 insertion mutations, a group the company says makes up about 9% of EGFR mutations. It tested two once-daily doses of the oral drug, 160 mg and 240 mg, each against platinum-based chemotherapy with pemetrexed, the current first-line standard. The main goal was progression-free survival, the time patients live without their cancer growing or spreading, as judged by independent reviewers who did not know which treatment each patient received. ArriVent disclosed the results in a Form 8-K filed before the market opened.

What the trial showed

On the higher dose, median progression-free survival was 11 months, compared with 9.5 months on chemotherapy. The hazard ratio of 0.75 points to an estimated 25% lower risk of progression or death, but the result fell short of statistical significance, with a p-value of 0.0654 and a confidence interval running from 0.55 to 1.02, which leaves open the possibility of no benefit at all. The 160 mg dose came in below chemotherapy on the median, at 8.4 months.

Other measures looked better. When the trial's own investigators read the scans, median progression-free survival was 11.1 months on the 240 mg dose against 7.1 months on chemotherapy, a hazard ratio of 0.61. By independent review, 60% of patients on the higher dose had a confirmed tumor response, compared with 33% on chemotherapy. Overall survival data are not yet mature, though the company said it saw a trend toward improvement. Severe treatment-related side effects, grade 3 or higher, occurred in 26% of patients on 240 mg and 40% of those on chemotherapy, and ArriVent said it found no new safety signals.

Bing Yao, ArriVent's chairman and chief executive, called the results "disappointing" and said the trial "did not show a meaningful improvement" in progression-free survival over chemotherapy. The company is evaluating the full data set before it decides on "the most appropriate development path for firmonertinib."

A stronger-than-expected comparison arm

By one analyst's account, the problem was the comparison arm rather than the drug. Jeet Mukherjee, an analyst at BTIG, said the trial appears to have failed mainly because the chemotherapy arm delivered 9.5 months of progression-free survival, against an expected 7.5 to 8 months, while firmonertinib's 11 months was in line with the expected 9 to 11 months.

A rival approach has posted stronger numbers in the same group of patients. Last month, Cullinan Therapeutics and its partner Taiho reported that zipalertinib combined with chemotherapy produced median progression-free survival of 14.5 months, against 8.5 months for chemotherapy alone, at a planned interim analysis of the REZILIENT3 trial. That study added a drug to chemotherapy rather than replacing it and used a different design, so the two trials cannot be compared directly.

What is left for ArriVent

Firmonertinib is ArriVent's lead drug candidate, and FURVENT was one of two pivotal trials meant to establish it as a first-line treatment for uncommon EGFR mutations. The second, also a global Phase 3 study, is testing it in patients with a different group of those mutations. Kaveri Pohlman, an analyst at Clear Street, called Tuesday's result "a meaningful setback" for the exon 20 opportunity but said the other program has clinical support. The drug is already approved in China for several lung cancer uses and holds a U.S. breakthrough therapy designation for this first-line setting.

ArriVent had $373.1 million in cash and investments at the end of June, which it said would fund operations into 2028, and it used $81.5 million of cash in operations in the first half of the year. It is also developing two early-stage antibody-drug conjugates, for gastrointestinal cancers and for ovarian and endometrial cancers.

ArriVent's shares, which trade on Nasdaq under the symbol AVBP, were down 48.5% at $14.65 at 3:24 p.m. ET, according to cnbc.com market data, after falling as much as 60% to $11.36, a 52-week low, earlier in the session. That gave the company a market value of about $722 million, roughly twice its June cash balance. An exchange-traded fund that tracks biotech stocks fell 3.6%, while the S&P 500 rose 0.7%.