Vertex’s rare lung disease drug hits phase 2 goal—but still winds up on the scrapheap

Vertex Pharma
Vertex announced the phase 2 data and program discontinuation eight months after it abandoned a different molecule, VX-814, because it caused abnormally high levels of liver enzymes in a phase 2 study. (Vertex Pharma)

It’s back to the drawing board for Vertex as the biotech ditches another prospect it was developing for alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder that can lead to liver and lung disease.

Patients with AATD have a mutation that causes them to produce abnormal forms of the alpha-1 antitrypsin (AAT) protein. These misfolded proteins get trapped in the liver instead of being released into the blood like normal AAT proteins. The buildup of abnormal AAT in the liver, coupled with low levels of AAT in the blood, can result in liver and lung disease.

Vertex’s VX-864 is a “corrector molecule,” designed to prevent the misfolding of AAT and increase plasma levels of AAT. After 28 days, three dose levels of VX-864 beat placebo at boosting patients’ plasma AAT levels in a phase 2 study. But even though the trial technically succeeded, the drug’s effect was so small that the company deemed it unlikely to “translate into substantial clinical benefit.”

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“As such, Vertex will not advance VX-864 into late-stage development and instead will advance novel small molecule correctors with the potential for increased clinical efficacy into the clinic,” the company said in a statement Thursday afternoon.

The company plans to start clinical trials for other drug prospects in 2022, according to the statement.

Vertex’s stock dropped as much as 14% in after-hours trading.

Vertex announced the phase 2 data and program discontinuation eight months after it abandoned a different molecule, VX-814, because it caused abnormally high levels of liver enzymes in a phase 2 study.

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 at the time. What’s more, data analyses showed that only small amounts of the drug went where it was supposed to go.

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The news was a blow 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 at the time.

Having culled VX-814, Vertex turned to VX-864, a compound that is “structurally distinct” from VX-814 and was already in a phase 2 study. Now, with VX-864 on the scrapheap, the company will turn to its preclinical pipeline.

“We are encouraged by the clear separation of AAT levels in the VX-864 treated groups versus placebo and the favorable safety profile,” Carmen Bozic, M.D., Vertex’s chief medical officer and executive vice president of global medicines development and medical affairs, said in the statement. “Based on these findings, we remain committed to developing transformative treatments for AATD and are working with urgency to translate the learnings from this study to optimize the next set of small molecule correctors so that we can fully realize the potential that this class of molecules may hold for people living with this disease.”