Vertex’s triplet win leaves price the only question

Vertex Pharmaceuticals’ grip on cystic fibrosis looks like it will get even tighter. The company’s emphatic phase III win with its first triplet yesterday will have disappointed any rivals hoping for a late-stage slip-up.

Competitors, including Abbvie and Proteostasis, are well behind Vertex in the race to develop a CF triplet, which could treat 90% of cystic fibrosis patients. With its massive head start Vertex might be emboldened to set the price of its triplet high, but with payers already pushing back against its existing CF drugs the group might have to tread carefully.

Cost conundrum

Leerink analyst Geoffrey Porges speculated that Vertex’s triplet could be priced similarly to its approved doublet, Symdeko, at $233,000 a year. Still, the US cost watchdog Icer concluded earlier this year that Symdeko would have to be $165,000 cheaper than this to be cost effective.

How a triplet stacks up in terms of cost-effectiveness will depend on what experts believe it adds in terms of efficacy. And the data reported yesterday showed an impressive clinical benefit with the first of Vertex’s two investigational triple combos to report: ivacaftor and tezacaftor – the components of Symdeko – plus VX-659.

Vertex carried out two phase III studies: one in patients homozygous for the F508del mutation in the CFTR gene, and the other in patients with one copy of the F508del mutation and one minimal function mutation (known as F508del/Min).

Vertex already dominates the homozygous population with its current therapies, Symdeko, Orkambi and Kalydeco, but it believes that it can improve on its existing drugs. F508del/Min patients, meanwhile, have no treatment options currently.

This looks likely to change soon. In the F508del/Min trial, patients on the Vertex triple saw a 13 percentage point improvement from baseline in ppFEV₁, versus a one-point decline for patients taking a triple placebo, after four weeks of treatment.

In the F508del homozygous study patients taking the triple saw a 10-point improvement in ppFEV₁ over a control group taking tezacaftor and ivacaftor alone, at four weeks.

The data are in line with phase II results, and Stifel analyst Paul Matteis described them as a “best case scenario” for Vertex.

The same cannot be said for the company’s rivals. Abbvie’s triplet, recently acquired in full from its partner Galapagos, has only just yielded phase I data, and these were lacklustre (Abbvie’s low-risk bet could challenge Vertex on price, 25 October 2018).

Meanwhile, Proteostasis is set to report phase III data with its own triplet later this year. However, recent results with a doublet comprising PTI-808 and PTI-801 – which are also part of its triplet – were confusing at best.

Vertex’s win could also be bad news for any patients hoping that the group’s monopoly in CF might be broken; the high price tags for its drugs have meant that payers in the UK, for example, have refused to fund the therapies.

Choices, choices

Vertex should have a straightforward path to approval, and could launch a triplet in 2020,  Leerink analysts estimate.

First, though, the company will choose which of its triplets to take forward. As well as VX-659 plus tezacaftor and ivacaftor, Vertex has another shot on goal: VX-445 plus tezacaftor and ivacaftor, due to report phase III results in the first quarter of 2019.

Leerink’s Mr Porges wrote that “it is hard for us to see” how the ‘445-based combination could be better than the one using ‘659, although he added that secondary endpoints, evaluations of patient histories, and effects on weight changes and overall hospital and medical costs would also enter into the calculation.

Vertex added $2bn to its market cap yesterday on the back of the triplet data, and its stock is not too far off a five-year high. It seems like the only thing that could challenge the group’s dominance in CF now is a pricing misstep.