Vertex Falls After Announcing Key Asset for Rare Disease Will Not Advance

Vertex_Craig F. Walker/The Boston Globe via Getty

Craig F. Walker/The Boston Globe via Getty Images

Shares of Vertex Pharmaceuticals fell more than 13% in premarket trading after the company announced it will not advance a novel small molecule corrector of the Z-AAT protein into a Phase III study for a rare disease that can lead to complications of the liver and lungs.

On Thursday, Boston-based Vertex announced that treatment with VX-864 led to a statistically significant increase from baseline in plasma functional AAT levels compared to placebo in a Phase II study in people with alpha-1 antitrypsin deficiency (AATD) with the PiZZ genotype. 

While the results provided proof-of-mechanism, Vertex said the magnitude of efficacy observed in the mid-stage study was unlikely to translate into substantial clinical benefit for these patients. As a result, VX-864 will not advance into late-stage development.

Data from the study showed that all VX-864 dose groups demonstrated highly statistically significant increases in plasma fAAT levels after day 28 of treatment. Patients who received VX-864 saw a mean increase of 2.2 to 2.3 micromolar in fAAT levels across the three dose groups studied compared to placebo. The primary outcome measures were the mean change from baseline in plasma fAAT levels at day 28 compared to placebo as well as safety and tolerability of VX-864.

Carmen Bozic, executive vice president of Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex, said this was the first time researchers have shown that dosing a small molecule corrector of the Z-AAT protein resulted in significant elevations in both functional and antigenic levels of AAT in people with this rare disease. While the efficacy data wasn’t strong enough to advance this asset into Phase III for this indication, Bozic said the company remains committed to developing transformative treatments for AATD and will use the findings from this study to push forward into the next stages of research. 

“We… 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,” Bozic said in a statement. 

AATD is a rare, genetic disease characterized by a protein folding defect that can lead to diseases of the liver and lungs. AATD is caused by changes in the SERPINA1 gene that encodes the AAT protein. The most common form of AATD occurs in people with the PiZZ genotype. 

In those patients, SERPINA1 causes the body to produce misfolded AAT protein that gets trapped inside the liver, which can lead to unchecked inflammation. There is currently no cure for AATD. There are also no treatments that target the underlying protein folding defect that is the cause of the disease, Vertex said. 

VX-864 was well tolerated, and the drug candidate did demonstrate proof-of-mechanism with what Vertex has called a “rapid, consistent and clear effect on functional and antigenic AAT levels.” The company said the data collected in this study is expected to enable a future small molecule corrector approach in AATD. In addition, Vertex expects rapid advancement with its portfolio of new molecules that it believes have the potential for greater clinical efficacy. Vertex expects these small molecules can enter the clinic in 2022.

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