Vertex gets early okay for cystic fibrosis triple Trikafta in US

Vertex Pharma has claimed an ultra-fast approval in the US for Trikafta, its three-drug combination that provides a treatment option for up to 90% of patients with the genetic disease cystic fibrosis.

The FDA green light comes just three months after Vertex filed the breakthrough-designated triple as a treatment for patients 12 years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Trikafta is based on ivacaftor and tezacaftor – which feature in Vertex’ two-drug combinations Symdeko and Orkambi – as well as a new compound called elexacaftor (VX-445) which was one of two add-on compounds put through their paces in phase 3 testing.

It’s widely held as a pivotal drug that could transform treatment for many patients with CF, and accelerate Vertex’s financial growth.

Approval had not been due until early 2020, and the early go-ahead plus a list price ($311,000 per year) roughly in line with the older drugs has analysts predicting rapid growth to blockbuster sales levels.

Some analysts had expected Vertex to pitch the price of Trikafta a little lower, given its broader reach, but of course the list price doesn’t take into account discounts and rebates that may be negotiated with healthcare payers in the US.

Vertex’ first CF drug Kalydeco (ivacaftor) was introduced in 2012, and was suitable for around 4-5% of patients with CF. Additional two-drug combinations Orkambi (lumacaftor/ivacaftor) and Symdeko/Symkevi (tezacaftor/ivacaftor) in 2015 and 2018, respectively, have extended the coverage to around half of the CF population.

Those therapies are already bringing in blockbuster sales – estimated to be on track to reach $2.6 to $3.7 billion this year – but Trikafta’s expanded coverage could make it a $6.6 billion product in its own right by 2025, according to SVB Leerink analyst Geoffrey Porges.

That will inevitably involve cannibalisation of Vertex one- and two-drug CF therapies, but investors saw the net positive and lifted shares in the company by 4% yesterday after the news came in and another 2% in after-hours trading.

Analysts at William Blair predicted earlier this year that Vertex’s overall CF franchise would bring in more than $10 billion a year in peak sales, representing around 80-85% of the total CF market.

The approval of Trikafta will make “a novel treatment available to most cystic fibrosis patients, including adolescents, who previously had no options,” said acting FDA Commissioner Ned Sharpless.

Vertex estimates that around 6,000 new CF patients will be eligible for treatment with Trikafta in the US, adding to the 12,000 already in line for treatment with its older drugs.

The importance of the new drug is reflected by the fact that the FDA gave it the full-house of tools used to speed up approval, including priority review, fast track, breakthrough therapy, and orphan drug designations, said Sharpless.