Boehringer Ingelheim Reveals Battle Plans For Olmutinib
Executive Summary
Boehringer Ingelheim has revealed its Phase III plans for its third-generation EGFR inhibitor, olmutinib, a product that was recently approved in its first market, South Korea, but still faces significant competition in this crowded area.
Boehringer Ingelheim GMBH Boehringer Ingelheim has announced Phase III plans in non-small cell lung cancer for olmutinib, the third-generation epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor (TKI) it licensed from Hanmi Pharmaceutical Co. Ltd. last July.
Following the product's recent success in its originator's home market, South Korea, BI says it will comprehensively investigate olmutinib as a monotherapy in the ELUXA clinical trial program in a range of settings as well as in combination with investigational and existing anti-cancer drugs, including Merck's anti-PD-1 therapy, Keytruda (pembrolizumab).
Olmutinib is one of a number of drugs being positioned against non-small cell lung cancer (NSCLC) that has developed resistance to the earlier EGFR inhibitors such as AstraZeneca PLC's Iressa (gefitinib) and Roche/Astellas Pharma Inc.'s Tarceva (erlotinib). Most initial responders to these therapies develop resistance through secondary mutations, the most common is the T790M mutation, which occurs in about 60% of patients.
Two of the ELUXA studies will be Phase III trials set to begin this year; one comparing olmutinib in comparison to standard, platinum-doublet chemotherapy for patients with EGFR T790M mutation-positive lung cancer, whose disease progressed on one prior EGFR-TKI treatment (ELUXA 2). The other (ELUXA 3) will investigate olmutinib as a first-line treatment compared to BI's second-generation EGFR TKI, Gilotrif (afatinib), in patients with EGFR mutation-positive NSCLC.
Another smaller Phase I/II trial (ELUXA 4) to start in 2016 will test it in Japanese patients with EGFR T790M-positive NSCLC. And a further Phase II trial will be the first trial to prospectively use blood-based biomarker testing to select patients with EGFR T790M mutation-positive NSCLC where a needle biopsy may not be appropriate. This is important to reduce the need for repeat biopsies to determine resistance patterns.
The drug will also be tested in combination with a variety of other products, including Keytruda, Gilotrif, BI's IGF ligand-neutralizing antibody BI 836845, BI's triple angiokinase inhibitor Vargatef (nintedanib) and Roche's Avastin (bevacizumab).
Analysts at Datamonitor Healthcare said there are at least three other candidates targeting patients with the T790M mutation: Novartis's EGF816, Astellas's naquotinib (ASP8273), and Pfizer's PF-06747775 that will likely all initially target patients who progress on first-line EGFR tyrosine kinase inhibitors due to the T790M mutation. "Furthermore, these candidates have demonstrated little activity against wild-type EGFR, which reduces their toxicity in comparison to early-generation EGFR inhibitors and enhances their potential to be used in the first-line setting," analysts said.
While targeting the T790M mutation looks to be an effective strategy, they will still have to go up against AstraZeneca's newly launched third-generation EGFR inhibitor Tagrisso (osimertinib), although another rival, Clovis Oncology Inc.'s rociletinib, left the field in May in anticipation of an FDA approval rejection, after it was cast into the shade by Targrisso at its oncologic drugs advisory committee meeting in April. (Also see "Clovis Pulls Plug On Rociletinib On Expected FDA Rejection" - Scrip, 5 May, 2016.)
Hanmi has licensed the rights to olmutinib to Boehringer Ingelheim in all markets except South Korea, China, and Hong Kong, and its approval in South Korea will help accelerate the drug's clinical development and Boehringer Ingelheim will aim to gain approval by 2017. [See Deal]
But BI is not the only company to look to combination use to try to differentiate its early phase T790M inhibitor. For example, Novartis has begun two studies testing EGF816 with its c-Met inhibitor capmatinib (Incyte) and with Keytruda's rival immunotherapy from Bristol-Myers Squibb, Opdivo (nivolumab) in EGFR mutation-positive patients.