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Second Vertex triple combo succeeds in cystic fibrosis, setting up crucial choice

  • An experimental triplet of drugs from Vertex Pharmaceuticals significantly improved lung function in people with cystic fibrosis across two Phase 3 studies, showing similar efficacy to another triple combination of the biotech’s that succeeded late last year. 
  • In one study, Vertex’s regimen of VX-445, tezacaftor and ivacaftor delivered a mean absolute improvement over triple placebo of 13.8 percentage points in patients with one F508del mutation and a minimal function mutation, the company announced. In the other, enrolling individuals with two F508del mutations, the combination improved lung function by 10 percentage points over placebo plus tezacaftor and ivacaftor. 
  • Vertex will wait, however, until it has final 24-week data from both combination regimens before it decides which to submit to regulators, a step expected to occur in the U.S. by the third quarter. Tezacaftor and ivacaftor are currently marketed as a doublet regimen under the brand name Symdeko. 

Vertex has a consequential choice to make. Triple combination therapy is a central part of the biotech’s strategy to expand the population its drugs can treat to nearly all cystic fibrosis patients. 

But the new data on its regimen containing VX-445 looks similar to earlier Phase 3 results for the triple containing VX-659. Vertex only plans to submit one to regulators for approval, so it will wait for final 24-week data to determine if one presents a more attractive clinical profile. 

The company characterized both regimens as generally well-tolerated and plans to later disclose more detailed data on whichever combination with which it decides to proceed. 

“We were previously of the belief the company would move forward with VX-659, as the VX-445 regimen did not look as clean in the Phase II in our view,” wrote Jefferies analyst Michael Yee in a note to clients. “However, with the data looking similar between the two regimens to date, we think it is a prudent move by the company to wait for more data.”

Investors, however, appeared disappointed by Vertex’s caution, sending shares in the company down nearly 4% Wednesday. 

Vertex enjoys a strong competitive position in cystic fibrosis, a genetic disease marked by defective or missing CFTR proteins. Success with a triple combination would help to keep that advantage, although rivals remain. AbbVie, for example, recently took full control of cystic fibrosis drugs it developed with Galapagos and plans to advance triple combination regimens, too. 

Over time, whichever triple combo Vertex chooses could eventually replace Orkambi (lumacaftor/ivacaftor) if approved.