Summit Lung Cancer Drugs Insufficient Key Survival Targets in Global Research, Questions about FDA Approval
A carefully observed summit drug for lung cancer has improved in a pivotal study measure of the measurements among patients treated with the treatment, but the final analysis of Western patients is not enough to be statistically significant, a shortage that may lead to blockbusters hoping to obtain regulatory approval from the United States and Europe.
The results are important because they are Phase 1 3 data for emerging drug classes, namely bispecific antibodies designed to block two targets PD-1 and VEGF. The results are also noteworthy, as Ivonescimab stood out from data a year ago, a monoclonal antibody that blocked PD-1 in head-to-head studies. Ivonescimab's dual approach can help patients whose disease cannot respond adequately to PD-1 inhibitors.
The positive results reported last year came from patients admitted in China, based on Akeso, the inventor of Ivonescimab. Summit has the drug in most parts of the world. Global drug test results for global drug tests at the World Conference on Lung Cancer in Barcelona on Sunday.
The third phase of the study recruited 438 patients with locally advanced or metastatic non-small cell lung cancer. Ivonescimab was tested with chemotherapy and compared with placebo plus chemotherapy. The trial, called Harmoni, has two main goals: measuring progression-free survival, which is the long lifespan of the patient, and the overall survival rate, which is the time after the patient starts treatment.
In the scheduled data analysis reported in May this year, the median progression-free survival of Ivonescimab and chemotherapy was 6.8 months compared with 4.4 months in the control group, which was statistically significant. The main analysis also shows a positive trend in overall survival. The statistical significance of this measure is key, as the FDA says achieving this goal is a requirement for regulatory approval.
At the primary analysis, the median number of Asian patients was 30 months. The latest results include the long-term appearance of Western patients to increase their follow-up time, but the median follow-up for these patients was only 13.7 months. The final analysis showed that the median overall survival of these Western patients was 16.8 months, participants who received ivonescimab and chemotherapy, and 14.0 months of placebo plus chemotherapy. But among North American patients, especially in the study drug department, the overall survival was not achieved, with the placebo group being 14.0 months. Summit said the safety and tolerance of the drug were consistent with earlier drugs tested with chemotherapy and no new safety signals were reported.
In a note sent to investors, Daina Graybosch, an analyst at Leerink Partners, said Harmoni's trial design failed to test whether the signals observed in Chinese patients would be converted globally.
“We don't think the FDA will be likely to be approved by Harmoni, nor will it give Summit a large valuation that investors expect – over $15 billion upfront, more than half of upfront,” she said.
Graybosch added that readers confirmed the hypothesis that patient survival data reported in China would degrade the drug in patients in North America and Europe. However, judging from the limited information provided at the conference, it is not clear what the driver of this degradation is. For Leerink, more information is needed to appreciate the relevance of the Harmoni study as a benchmark for other bispecific antibodies performed after PD-1 (or PD-L1) and VEGF.
Bispecific antibodies against PD-(L)1 and VEGF are considered as potential as a backbone of novel cancer drug combinations. Other companies developing bispecific antibodies for both targets include Bristol Myers Squibb and Biontech, which announced a wide range of partnerships in June. Biontech acquired its competitor BNT327 from its acquisition of China Biotheus. Other companies developing bispecific antibodies to PD-(L)1 and VEGF include Merck, Instil Bio and Pfizer, all of which have obtained drugs from Chinese companies.
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