Vertex, one of the world's largest biotechnology companies, has been trying to prove it can succeed outside of cystic fibrosis, a disease that's become treatable thanks to four approved drugs it has developed.

So far, though, the Boston-based company has run into setbacks, with the latest coming Thursday in the form of fresh data from a highly anticipated clinical trial. Technically, the trial was positive, as it found Vertex's experimental drug, VX-864, was able to significantly boost a protein vital to liver and lung health in patients with a rare, genetic disease that leaves them without much of it. Vertex said the results validate the company's underlying theory on how to treat the disease, known as alpha-1 antitrypsin deficiency.

However, the company also said the data, while positive, suggest its drug isn't potent enough to substantially benefit patients. Vertex has therefore decided not to move it forward, and instead focus on getting more potential treatments for AAT deficiency into clinical testing next year.

"We believe we know why the magnitude of response wasn't where we thought it would be, so now we need to find the more potent and efficacious molecule that drives transformative therapeutic benefit," a Vertex spokesperson wrote in an email to BioPharma Dive.

An estimated 100,000 people in the U.S. have AAT deficiency. No treatments have been approved specifically for the disease, but a few companies are working to change that. Aside from Vertex, U.K.-based Mereo BioPharma expects to have data from a mid-stage clinical trial of its AAT drug later this year. And at Arrowhead Pharmaceuticals, executives are hoping regulators can give a speedy review to ARO-AAT, an experimental drug also in mid-stage development.

For Mereo and Arrowhead, more positive data could propel the companies closer toward their first approved products. But for Vertex, a victory in AAT deficiency would be symbolic.

Vertex is a proven powerhouse in cystic fibrosis drug development, creating products that can treat 90% of the patient population. Last year, the biotech recorded $6.2 billion in revenue, and expects another almost $7 billion for 2021. Yet, that track record has investors questioning where Vertex could find success next.

On that front, Vertex has run into obstacles. For example, the company stopped work on an earlier AAT drug because of safety issues. And in pain, the company is still looking for a breakthrough moment after two candidates didn't deliver promising enough results in clinical tests.

Vertex does think it's heading in the right direction in AAT deficiency, though. In the study of VX-864, all the tested doses of the drug showed "highly statistically significant increases" in functional levels of the protein compared to placebo.

Specifically, patients treated with Vertex's drug had a mean increase of 2.2 to 2.3 micromolars in functional protein compared to placebo. But the improvement was too small to increase patients' protein levels above what Vertex thinks will be protective against disease, about 11 micromolars.

After treatment was withdrawn, per the study plan, protein levels in treated patients returned to baseline, which Vertex says is evidence of its drug's activity. 

And unlike its predecessor, VX-864 didn't elicit safety issues. Vertex said the drug was generally well tolerated, with all but one patient completing treatment. The company noted how no patients discontinued treatment due to adverse events, and that there were no serious adverse events tied to its drug.

Still, with VX-864 now shelved, Vertex may find itself under greater pressure to make sure other programs pan out, including a gene editing treatment for blood disorders that it's co-developing with CRISPR Therapeutics.

Vertex recently amended its partnership with CRISPR so that, in the event their treatment gets approved, it will get a larger split of any resulting profits. The revised deal, which Vertex spent $900 million to secure, suggests the biotech sees a multibillion opportunity for the program, according to analysts.

Shares in Vertex fell by more than 10% in postmarket trading on news of the study data, while Arrowhead climbed by more than 5%. 

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