- Bristol-Myers Squibb presented further data from its CheckMate-026 trial of Opdivo (nivolumab) in first-line non-small cell lung cancer (NSCLC) patients who expressed more than 5% of the PD-L1 biomarker in their tumor.
- Results showed that these low-expressing patients on Opdivo has a progression-free survival (PFS) of 4.2 months compared with 5.9 months for those on chemotherapy. The overall survival in this patient population was 14.4 months in Opdivo patients compared with 13.2 months for chemo patients.
- Unlike competitors that tested their PD-1 inhibitors in patients with high-expressing levels of the biomarker, Bristol used this study to see if the highly touted checkpoint inhibitors could work regardless of PD-L1 expression. The failure could put Merck & Co's Keytruda (pembrolizumab) ahead in the large market.
After a close start where Bristol-Myers Squibb's Opdivo had pulled ahead of Merck's Keytruda in the checkpoint inhibitors sales race, it now looks like Opdivo has lost ground to Keytruda. Back in August this year, Bristol faced a sharp fall in share price when the topline results from CheckMate-026 were announced. The more detailed analysis at ESMO has knocked the company back again, with a slump of around 8% in stock value.
In contrast, Merck had a more cheerful time at ESMO, which has lifted its stock by around 2% when the markets opened. In KEYNOTE-024, which studied Keytruda in high-expressing patients, Keytruda monotherapy cut the risk of disease progression by half and the risk of death by 40% in comparison with chemotherapy.
The FDA has granted Keytruda Breakthrough Therapy designation and priority review, and the PDUFA date is December 24, 2016 in first-line lung cancer for PD-L1-expressing patients.
Merck also presented some combination data for Keytruda, showing greater efficacy in lung cancer patients regardless of PD-L1 status when compared with chemotherapy alone. Jefferies analysts predict a larger market potential for PD-L1 drugs in combination with chemotherapy, based on current data and data due to read out during 2017.
Bristol remains hopeful that Opdivo still has potential in combination therapy, and the ongoing CheckMate-227 study, which combines Opdivo with Yervoy (ipilimumab), is in active recruitment at all levels of PD-L1 expression. The study will include over 2,000 patients, with Bristol management suggesting at ESMO that the study has been expanded and accelerated.
"The CheckMate -026 trial results strengthen our belief that the majority of previously untreated NSCLC patients may require combination therapy in order to experience an improved benefit versus chemotherapy," said Fouad Namouni, head of oncology development at Bristol-Myers Squibb. "With our broad lung cancer development program, which includes a robust Phase 3 trial evaluating the combination of Opdivo and Yervoy as first-line therapy, we will continue to aim for transformative options for the majority of lung cancer patients."
The lung cancer market is a huge one. WHO data shows that lung cancer is behind over 1.5 million deaths a year worldwide. NSCLC is one of the most common forms of the disease, making up around 85% of lung cancers overall. Opdivo is approved in pretreated NSCLC, and has a market dominance in second line treatment, with 60-70% share in squamous and 50-60% share in non-squamous NSCLC, according to Bristol.
However, Roche's Tecentriq, which could be approved in lung cancer this week, and Keytruda's approval in first line therapy in high PD-L1 expressors could have quite an impact on this market share. Bristol remains optimistic, citing its breadth of indications, established reimbursement from payers, and simple companion diagnostic as differentiators for the product.