Vertex, after setbacks, moves forward with second-generation rare disease drug

Vertex Pharmaceuticals is trying again at developing a drug for the rare, genetic disease alpha-1 antitrypsin deficiency after two earlier efforts fell short.

The biotech announced Tuesday that it has received clearance from the Food and Drug Administration to begin a clinical trial testing a new treatment for the condition, which is caused by the misfolding of a protein called AAT and damages the lungs and liver of affected individuals.

The study, which will enroll healthy volunteers, is a Phase 1 trial designed to measure the drugs safety and find an appropriate dose for further testing.

In addition, Vertex said it will also begin a nearly year-long Phase 2 study of an earlier drug that wasnt potent enough to advance into late-stage testing. While technically positive, the magnitude of treatment benefit observed in a mid-stage trial last year wasnt as large as Vertex was looking for. Further analysis of the study showed the drug reduced levels of a liver polymer in the blood of patients, however.

The new study will assess the effect of longer-term treatment on polymer clearance and whether it also yields greater increases in functional AAT protein.

By simultaneously advancing new, more potent molecules into the clinic and assessing the impact of longer-duration treatment, we expect to have both the assets and the data necessary to progress our AAT corrector program in 2023, said David Altshuler, Vertexs head of research and chief scientific officer, in the companys Tuesday statement.

Alpha-1 antitrypsin deficiency is one of several conditions Vertex has targeted in its efforts to build a pipeline of medicines that go beyond its historical focus on cystic fibrosis. While the drugs Vertex has made for the lung disease are clinically and commercially successful, pressure has increased for the company to prove it can do the same elsewhere.

It has some recent successes in that quest, reporting positive results for drugs to treat pain, kidney disease and Type 1 diabetes. Those findings have helped Vertex shares climb to all-time highs this year. Alpha-1 antitrypsin deficiency has been harder, though. Vertex stopped testing its first compound for the disease after reports of an early safety signal.

"Given the performance of the previous-gen AAT molecules, we think this is still a show-me story where we need to see strong efficacy data before making any conclusions," wrote Michael Yee, an analyst at Jefferies, in a Tuesday note to clients.

Vertex is also nearing submission of approval applications for a gene editing medicine its developing with CRISPR Therapeutics for sickle cell disease and beta thalassemia.