Vertex's big move beyond cystic fibrosis hits a wall with lung drug failure

Vertex Pharma
News that Vertex is canning VX-814 was “surprising and disappointing” for a program that “was widely thought to be the primary value driver” for Vertex outside of its cystic fibrosis drugs, JPMorgan analyst Cory Kasimov wrote Wednesday evening. (Vertex)(Vertex Pharma)

Vertex is pulling the plug on a treatment for a rare, inherited lung disease after the prospect caused abnormally high levels of liver enzymes in a phase 2 study.

It had been testing the drug, VX-814, against placebo in about 50 patients with alpha-1 antitrypsin deficiency (AATD), a genetic disorder in which low levels of the protein alpha-1 antitrypsin can cause liver and lung disease. With VX-814, Vertex sought to boost patients’ levels of that protein.

Investigators found “several patients” had elevated liver enzymes, with four of them having spikes more than eight times the upper limit of normal, the company said in a statement Wednesday afternoon. What’s more, data analyses showed that only small amounts of the drug went where it was supposed to go.

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"Based on the liver enzyme elevations observed, along with the determination that we would not be able to safely achieve targeted exposure levels with VX-814, we are discontinuing further development of this molecule," said Carmen Bozic, M.D., Vertex’s chief medical officer and executive vice president of global medicines development and medical affairs, in the statement.

Vertex’s stock dropped 9% in after-hours trading.

The news was “surprising and disappointing” for a program that “was widely thought to be the primary value driver” for Vertex outside of its cystic fibrosis drugs, JPMorgan analyst Cory Kasimov wrote in a note to clients Wednesday evening.

The company will continue a phase 2 study of a different drug, VX-864, in the same disorder, Bozic added. It has not made public how each of the drugs works, but Vertex said that VX-864 is “structurally distinct” from the discontinued compound. Vertex expects to see data in the first half of 2021.

“We acknowledge that the market may discount this next shot on goal; however, ‘864 is ‘structurally distinct’ from ‘814 and many times more potent, potentially offering a more optimal therapeutic window,” Kasimov wrote.

Vertex isn’t alone in the quest for an AATD drug. Just last week, Takeda bet $300 million upfront—with $740 million in promised milestones—on Arrowhead’s RNA interference treatment for liver disease linked to AATD.