Roche/Exelixis' Cotellic fizzles in pivotal melanoma study
To little surprise, Exelixis’ Cotellic — known chemically as cobimetinib — in combination with Roche’s Tecentriq, has failed a late-stage study as a frontline treatment for patients with a form of advanced melanoma.
The Alameda, California-based company’s $EXEL kinase inhibitor — out-licensed to Roche — was approved in 2015 in combination with the Swiss drugmaker’s Zelboraf (vemurafenib) for patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Cotellic generated roughly $61 million in global sales last year.
Results of the IMspire170 study were disclosed in a filing on Thursday. Exelixis said that Genentech (Roche), which sponsored the study, had found that cobimetinib + Tecentriq (atezolizumab) did not reduce the risk of disease progression or death compared to standard-of-care Keytruda, Merck’s flagship PD-1 immunotherapy, in treatment-naïve patients with BRAF V600 wild-type advanced melanoma.
Last year, in the Phase III IMblaze370 study, cobimetinib + Roche’s PD-L1 Tecentriq failed to significantly help patients with colorectal cancer live longer.
The likelihood of cobimetinib enhancing the impact of checkpoint inhibitor therapy in this melanoma tumor type (and others) was greatly diminished following last year’s disclosure of IMblaze370 data, Stifel’s Stephen Willey wrote in a note. “We don’t view this news as thesis-changing (i.e. cobimetinib is not part of our, or anyone’s, near- or longer-term EXEL thesis) and continue to view the displacement of 1L immunotherapy in this setting as unlikely.”
BMO Capital Market’s George Farmer said the data were inconsequential to his overall Exelixis investment thesis. “Phase 3 success (in the IMspire170 study) would only provide upside to existing cobi sales, which was not factored into our model.”
Another cobimetinib late-stage trial, called IMspire150 TRILOGY, is expected to read out before the end of this year. The study is evaluating a triplet combination of vemurafenib/cobimetinib/atezolizumab versus the doublet combination of vemurafenib/cobimetinib in patients with firstline BRAF mutant advanced melanoma. “(T)his triplet vs. doublet trial as more of a ‘check the box’ vs. an ‘expand the market’ exercise and, like IMspire170, don’t view IMspire150 topline results as a key catalyst for the stock,” Willey wrote.
“We also believe the ongoing evaluation of other triple-therapy combinations (BRAF/MEK/PD-1) in 1L BRAF-mutant melanoma by other, more-entrenched competitors would likely keep any enthusiasm related to a potential TRILOGY win appropriately muted.”
Exelixis’ fortunes largely rest on the potential of its TKI Cabometyx (cabozantinib) in the treatment of renal cell and hepatocellular carcinoma. Top-line results from the Checkmate-9ER trial, evaluating cabozantinib plus Bristol-Myer’s $BMY PD-1 Opdivo, versus Pfizer’s $PFE sunitinib, are expected in the first half of 2020.
But competition is fierce. Merck’s $MRK Keytruda has been approved in combination with Pfizer’s TKI Inlyta for RCC patients, as has German Merck’s checkpoint inhibitor, Bavencio, (in combination with Inlyta) for the patient population.
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