Dive Brief:

• Vertex will begin late-stage testing of one of its top drug prospects later this month, announcing on Tuesday plans for a Phase 2/3 clinical trial that will test the treatment in a genetic form of kidney disease.

• While the trial will run for approximately two years, Vertex designed it to have an interim analysis after 48 weeks that, if results are positive, could support an approval application to the Food and Drug Administration for the drug, known as VX-147.

• Vertex’s decision to advance VX-147 was based on recent data from a small study that showed the drug could treat a kidney condition called focal segmental glomerulosclerosis, or FSGS, by targeting proteins encoded by a gene known as APOL1. With the new, larger trial, Vertex will test VX-147 more broadly in patients with kidney disease and two mutations in the APOL1 gene.

Dive Insight:

VX-147 is one of Vertex’s most advanced experimental drugs and represents a test of the company’s efforts to prove itself outside of cystic fibrosis, the genetic lung disease for which it developed four now-approved therapies.

Research setbacks elsewhere have increased the pressure on Vertex to deliver, even as those cystic fibrosis medicines earn it billions of dollars in sales.

Promising results for VX-147 in December were a needed win and helped to back up Vertex’s belief that targeting APOL1 could be a way to treat kidney disease. Data from the trial, which enrolled 16 patients with FSGS, showed treatment with the drug could significantly lower urine protein levels, which typically rise as scarring hinders the kidney’s ability to filter blood.

Girish Nadkarni, a kidney disease doctor at Mount Sinai hospital in New York City, told BioPharma Dive at the time that the study was an “attractive proof-of-concept.”

The newly planned trial is designed to prove that VX-147 can lead to better patient outcomes, rather than just lower protein levels, and will assess the drug in APOL1-mediated kidney disease instead of FSGS specifically. The main objective will be to show treatment reduces the rate of decline in kidney function, measured by estimated glomerular filtration rate, versus placebo at two years.

But investigators will also measure the difference in eGFR rate at 48 weeks, alongside changes in protein levels. The earlier interim analysis could give Vertex an opportunity to seek accelerated approval should results show a strong benefit.

In a March 22 note to clients, RBC Capital Markets analyst Brian Abrahams described the trial’s design as a “middle ground” between seeking approval on protein levels alone — an aggressive “best case” scenario — and requiring Vertex to wait the full two years.

“In essence, we believe this keeps the door open for accelerated approval of ‘147, but the bar will likely be higher, as it is less certain whether 48 weeks will be long enough to demonstrate a clinically relevant difference in eGFR function across [APOL1-mediated kidney disease] indications unless the drug’s activity is very robust,” Abrahams wrote.

Vertex indicated in its statement that it had obtained the FDA’s buy-in on its trial plans, noting discussions with the agency.

The trial’s first, Phase 2 portion will enroll 66 patients between 18 and 60 years old who will be given a range of doses of VX-147. Once a dose is selected, the trial will advance into a Phase 3 stage and enroll an additional 400 patients.

Vertex estimates approximately 100,000 people in the U.S. and Europe have two APOL1 mutations and kidney disease marked by elevated protein levels. People with two mutations are likelier to have more aggressive disease than those who don’t.