AstraZeneca’s Imfinzi/tremelimumab will struggle to sit at first-line NSCLC table; Merck’s dominance, BMS’ niche biomarker offering generate preference, experts say

27 Aug 2018

AstraZeneca (LON:AZN) is unlikely to find a distinct spot for Imfinzi (durvalumab) combined with tremelimumab in the highly coveted first-line (1L) non-small-cell lung cancer (NSCLC) space due to competition with immunotherapy(IO) combinations with chemotherapy and a lack of biomarker or toxicity advantages over other IO-only combinations, said experts.

Merck’s (NYSE:MRK) Keytruda (pembrolizumab) is the frontrunner, with an estimated 80% market share in the 1L NSCLC space and NSCLC revenues potentially reaching USD 8.5bn by 2022.

On 27 July 2017, AstraZeneca announced that the Phase III MYSTIC trial (NCT02453282) of Imfinzi/tremelimumab failed on its progress-free survival (PFS) endpoint, resulting in a 15% stock drop. Overall survival (OS) endpoint data is expected in 2H. Prior to the MYSTIC announcement, analysts estimated USD 4bn peak sales for Imfinzi but now forecast USD 2.2bn by 2020. Other top NSCLC contenders include Bristol-Myers Squibb’s (NYSE:BMY) Opdivo (nivolumab) and Roche’s (SIX:ROG) Tecentriq (atezolizumab), estimated to make USD 3bn and USD 1.6bn, respectively.

Even if the Phase III MYSTIC study proves an OS improvement over chemotherapy, experts said the field has moved on to a Keytruda/chemotherapy combination as standard-of-care (SOC). This makes MYSTIC data interpretation tough, especially if any potential improvement is restricted to PD-L1 positive patients only, they said. Imfinzi is a PD-L1 inhibitor approved in the second-line for unresectable Stage III NSCLC and second-line metastatic urothelial cancer, while tremelimumab is an unapproved CTLA-4 inhibitor.

Experts said that Imfinzi’s uptake would be further hit by the inability to find a niche where Keytruda will not be applicable, as done by BMS with its tumor mutation burden (TMB) biomarker data for Opdivo/Yervoy (ipilimumab).

An AstraZeneca spokesperson declined to comment on the Phase III results or potential placement for Imfinzi/tremelimumab in the 1L NSCLC space.

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