Vertex's cystic fibrosis candidate exceeds hopes

Hugely encouraging preliminary pivotal data for Vertex Pharmaceuticals' VX-770 (Kalydeco) has prompted predictions that the first disease-modifying therapy for cystic fibrosis (CF) is nearing the market. Smashing prior expectations, the results were enough to send the already highly-valued Vertex shares rocketing 16% yesterday, to touch four-year highs of $44.50 (Event - Expectations building for Vertex's second pipeline shot, January 27, 2011)

As well as significantly improving patients' lung function, VX-770 also aided other physical symptoms such as weight gain. Vertex’ collaborator on the project, the Cystic Fibrosis Foundation, has called the findings “extremely exciting.” The company plans to file for approvals later this year while important data from a paediatric trial are due mid-year. The drug is only indicated for a very specific CF patient population, but analysts have already started pencilling in half-billion-dollar peak sales potential.

More than numbers

Two decades after discovering the key perpetrator of CF pathology as a mutated cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, a drug designed to restore that channel’s normal function appears to have passed muster.

Excitement is tempered by the fact VX-770 will probably only work patients with the G551D mutation – about 5% of CF sufferers. However the pill is being touted as a disease-modifier, as opposed to current treatment which addresses only symptoms.

“As a physician who has treated CF patients for many years, the VX-770 results are more than just numbers - they represent hope," said Dr Preston W Campbell III, executive vice president for medical affairs of the Cystic Fibrosis Foundation, in a statement. "These are important clinical outcomes, and the fact they were maintained through 48 weeks is very encouraging.”

The foundation will receive single-digit royalties on VX-770 sales.

Full data from the phase III Strive trial are expected at an upcoming conference. The first data showed lung function was improved much more than expected - double what some were predicting - and symptomatic exacerbations were alleviated. Patients said they felt “substantially better” on VX-770, with significantly more completely free of exacerbations than in the placebo group. Meanwhile the rate of side effects was in fact higher in the placebo arm.

The improvement in lung function is particularly significant since it comes on top of the other therapies patients continue to receive, Vertex pointed out.

Child data more important

Strive was conducted in patients over 12 years old, the average age being 25 years.

Vertex estimates more than half of all CF patients are 18 years or younger; average life expectancy is just 37 years.

Arguably more important, therefore, are upcoming data from Envision, a phase III programme in children aged 6-12 years old, expected mid-year.

"We believe it may be important to begin effective therapies with people as early in their lives as possible," Vertex's chief scientific officer Peter Mueller remarked.

Other mutations

Vertex plans to seek approval in the US and Europe later in the year, supported by data from Envision and third study called Discover. This ongoing phase II safety trial has recruited CF patients with the most common form of the disease – those that carry the F508delta mutation, incidentally the target audience of Vertex’ similar, mid-stage CF drug VX-809.

In fact, VX-770 and VX-809 are being studied as a combination therapy, and first clinical data is expected over the next few months. This will also be of great interest, in terms of the extra patients that could be treated, implying a much greater value for Vertex.

While VX-770 is not designed to treat F508delta mutations, which tend to be missing the CFTR channel rather than carrying a mutated form, a small but statistically significant decrease in the concentration of sweat chloride was seen, which is a marker of CFTR functionality. Vertex proposed that some carriers of the F508delta mutation may still have residual CFTR channels present. As such, VX-770 may be effective on a wider group of patients than previously thought.


If approved, VX-770 is likely to carry a high price tag, although the company would not be drawn on pricing strategy.

Mark Schoenebaum, analyst with ISI Group, noted yesterday that with an assumed price of $30-40,000 per year, VX-770 could generate $550m, pointing out that in the world of “ultra-orphan” drugs there is strong chance that price goes considerably higher. Writing today, Howard Liang of Leerink Swann echoed the sentiment, projecting peak sales in excess of $500m for Vertex’s entire CF franchise.

EvaluatePharma consensus, gathered prior to the news, was $220m in 2016 sales for VX-770.

A complete data set will be more telling of VX-770’s true potential. But if this efficacy is confirmed, and hepatitis C candidate telaprevir is approved in May, Vertex could have its two biggest growth drivers on the market by the end of 2012. 

Trial IDs Strive (Study 102) NCT00909532
Envision (Study 103) NCT00909727 
Discover (Study 104) NCT01117012
VX-809/VX-770 combination study NCT01225211

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