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Beating Keytruda a big task, Exelixis and Roche find

  • A combination of Cotellic and Tecentriq failed to beat Keytruda monotherapy in newly diagnosed patients with non-mutated melanoma in a Phase 3 trial, according to an announcement from Cotellic’s developer, Exelixis.
  • Cotellic and another Roche drug, Zelboraf, are used in combination to treat melanoma patients whose tumors have a specific mutation, raising questions over why the partners were testing Cotellic in non-mutated patients.
  • A triple combination of Cotellic, Zelboraf and Tecentriq is in a Phase 3 trial that could yield results by the end of 2019. Success will be more essential for Roche and Exelixis in this trial as competitors are testing similar combinations in melanoma.

Merck & Co.’s immunotherapy Keytruda (pembrolizumab) is a tough competitor to beat. In this trial, Roche, Exelixis’ marketing partner, tested Cotellic (cobimetinib) and Tecentriq (atezolizumab) against Keytruda in first-line patients. Cotellic is already approved in combination with Roche’s Zelboraf (vemurafenib) in early-stage patients.

The difference is that the Cotellic-Zelboraf combination works in patients with specific mutations called BRAF V600E or V600K, and the Cotellic-Tecentriq trial did not specify whether patients needed to have that mutation.

Tecentriq is not approved in melanoma, although since it acts on the same immunological pathway as Keytruda, there is reason to believe it could have some benefit. The trial’s failure to show that adding Cotellic to Tecentriq could not delay disease progression or death compared to Keytruda by itself shows the potency of the Merck drug.

It is not the first time this combination has failed to best competitors. A trial last year failed to show improvement on Bayer’s Stivarga (regorafenib) in colorectal cancer.

Cotellic is not a big seller for either Roche or Exelixis. Roche reported global sales of 15 million Swiss francs and Exelixis $2.6 million in sales and licensing revenue in the first quarter of 2019.

That is revenue the two partners will be eager to protect, nonetheless. The combination of immunotherapies like Tecentriq and small-molecule kinase inhibitors like Cotellic and Zelboraf is being tested by a number of companies in melanoma, including Keytruda with the Novartis agents Tafinlar (dabrafeinb) and Mekinist (trametinib).

A combination of Tecentriq, Cotellic and Zelboraf is in a Phase 3 trial that could read out by the end of 2019, Stifel analyst Stephen Willey wrote in a June 20 note to clients. He characterized the trial as a “check the box” exercise to potentially protect rather than expand market share. In the event of a win, Willey wrote that the ongoing triple-combination trials of competitors will keep enthusiasm for Roche-Exelixis “appropriately muted.”