Abstract
Bristol Myers Squibb's acquisition of Mirati Therapeutics is poised to strengthen the former's position in the targeted therapy market, not only with the KRASG12C inhibitor adagrasib but also with Mirati's other assets, including a potential first-in-class PRMT5 inhibitor.
The global KRAS inhibitor market is looking robust, with strategic analysis company Precedence Research, for instance, valuing it at $102 million in 2022 and projecting that it will exceed $165 million by 2032. In an effort to compete with other pharmaceutical giants and capture market share, Bristol Myers Squibb (BMS) has acquired San Diego, CA–based Mirati Therapeutics for $58 per share in a buyout valued at more than $4.5 billion.
“The transaction, which is consistent with BMS's capital allocation strategy, strengthens and diversifies our oncology portfolio and augments our growth profile for the second half of the decade,” said BMS's Chief Medical Officer and Head of Global Drug Development Samit Hirawat, MD.
That growth is likely to be driven in the short term by Mirati's flagship drug, adagrasib (Krazati), the second KRASG12C inhibitor to receive accelerated FDA approval for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring the KRASG12C mutation. Adagrasib's main competitor is first-in-class sotorasib (Lumakras; Amgen); recent news that the FDA's Oncologic Drugs Advisory Committee found progression-free survival data from CodeBreaK 200, a confirmatory phase III trial for sotorasib, to be uninterpretable bolsters the prospect that BMS can take advantage of adagrasib's position in the market.
Even though neither adagrasib nor sotorasib has full approval yet, BMS has some advantages in the KRASG12C inhibitor space beyond no history of regulatory setbacks. Findings from the phase II KRYSTAL-7 trial and a cohort of KRYSTAL-1, a phase Ib study, have demonstrated the feasibility of combining adagrasib with the PD-1 inhibitor pembrolizumab (Keytruda; Merck) as first-line treatment for NSCLC, with an objective response rate (ORR) of 49% among 53 evaluable patients. Furthermore, in 19 patients from KRYSTAL-1 with central nervous system metastases who were radiographically evaluated after treatment, the ORR was 42% and the median overall survival was 11.4 months (J Clin Oncol 2023;41:4472–7), whereas patients with new or untreated brain lesions were excluded from Amgen's sotorasib trials.
It's not just adagrasib that played a role in BMS's decision to buy Mirati, but the biotech's other targeted therapy candidates as well. For instance, MRTX1719 is a potential first-in-class agent designed to exploit synthetic lethality by selectively inhibiting PRMT5 in the presence of MTA, which is elevated in MTAP-deleted cancers. It's now in phase I development, and current Mirati shareholders will get a voucher for an additional $12 per share upon an accepted FDA filing. Two other Mirati candidates of interest are MRTX0902, a SOS1 inhibitor (also in phase I), and MRTX1133, which targets the KRASG12D mutation.
“We believe Mirati's assets have the potential to change the standard of care in multiple cancers, both as stand-alone therapies and in combination with our existing pipeline,” explained Hirawat. In particular, the patent for MRTX1133 represents an opportunity for BMS, given that there is no effective KRASG12D inhibitor as yet and this mutation is predominant in pancreatic and colorectal cancers.
BMS's “resources will likely assist in expanding the patient subsets these compounds are tested in, which may improve the chance of finding a tumor subtype that will benefit,” said Timothy Burns, MD, PhD, of the University of Pittsburgh in Pennsylvania. “The downside of BMS acquiring Mirati is that its oncology focus has not traditionally been in the targeted therapy space, so they will need to lean on the knowledge of the company they acquired,” he concluded. –Myles Starr
For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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