- Vertex has selected the three-drug cystic fibrosis treatment it intends to file for regulatory approval, with submissions in the U.S. and Europe expected later this year.
- The biotech has been testing tezacaftor and ivacaftor, active ingredients in its marketed therapy Symdeko, in separate combinations with two experimental drugs called VX-445 and VX-659. While both regimens scored positive Phase 3 data, Vertex said the one containing VX-445 is advancing because of several attributes, including a more favorable safety and tolerability profile as well as the ability to co-administer it with hormonal contraceptives.
- VX-659, meanwhile, is essentially shelved. In an email to BioPharma Dive, a spokesperson wrote that Vertex does not intend to move forward with the drug or out-license it.
Vertex has said around half of all cystic fibrosis patients are eligible to take one of its three marketed products: Kalydeco (ivacaftor), Orkambi (lumacaftor/ivacaftor) and Symdeko (tezacaftor/ivacaftor and ivacaftor). But an approved triplet would bump that figure up to around 90% by the company's estimates.
Such an approval could come as early as next year, since Vertex intends to file its combination of tezacaftor, ivacaftor and VX-445 — now called elexacaftor — in the U.S. during the third quarter and in the European Union in the fourth quarter.
Wall Street analysts foresee the triplet easily winning over regulators. More challenging, however, will be getting on payers' good side. While Vertex secured payer support for its products in many countries, there has been pushback in France and the U.K., two of the world's largest pharmaceutical markets.
"[W]e continue to expect negative pressure on price as the company transitions to products with even larger addressable patient populations," SVB Leerink analyst Geoffrey Porges wrote in a May 30 note. "This trend was a part of our recent downgrade of Vertex' stock, and remains our main concern about the company’s outlook and value."
Perhaps most notably, the U.K.'s National Institute for Health and Care Excellence has openly feuded with Vertex over the list prices set for Orkambi and Symkevi (Symdeko's branded name in Europe), which are in the high $200,000 range. On its end, Vertex maintains that the English government isn't evaluating drug value appropriately.
While the U.K. has been pain point, revenue from Vertex's drugs is still growing quickly. Combined net sales from Kalydeco, Orkambi and Symdeko hit $857 million during the first quarter, up about a third from the same period a year prior.
Vertex expects its triplet to also do well.
"Given the strength of the efficacy and safety data seen to date for the VX-445 triple combination regimen, and based on our experience with the launches of our other CF medicines in populations with significant unmet need, we would expect rapid uptake of the medicine, if approved," the Vertex spokesperson wrote.
The company's confidence stems from two late-stage clinical trials that each succeeded and will serve as the basis for the triplet's approval.
The trials, one larger and one smaller, tested two kinds of cystic fibrosis patients based on their alleles. The larger enrolled patients with a mutation called F508del on one allele and a minimal function mutation on the other, whereas the smaller study enrolled patients with F508del mutations on both alleles. F508del is the most common mutation found in cystic fibrosis.
Data from the larger, 24-week study showed that patients treated with Vertex's regimen had a mean absolute improvement of 14% from baseline in a measure of lung function called percent predicted forced expiratory volume in one second (ppFEV1). It also found a 63% reduction in the annualized rate of pulmonary exacerbations compared to the placebo group.
The smaller, four-week study also found patients treated with Vertex's regimen experienced a statistically significant improvement on ppFEV1.
Rates of discontinuation were low across both investigations. Serious adverse events were observed for 14% and 4%, respectively, of the patients in the experimental arms of the larger and smaller trials.
Vertex is looking to secure an approval for cystic fibrosis patients aged 12 and older who have one F508del mutation and one minimal function mutation, as well as those who have two F508del mutations.
The three-drug treatment that included VX-659 also performed well in Phase 3 testing, but Vertex said it sees more patients benefiting from the VX-445 regimen. The company didn't disclose additional data on VX-659 in its Thursday announcement.
"While we can't know for sure we'd doubt that a safety issue manifested for -659; instead, it appears to us that the totality of the -445 data, considered alongside other [non-Phase 3] variables, represents a very high bar," Stifel analyst Paul Matteis wrote in a note to clients.