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Setback for Vertex’s cystic fibrosis challenger Proteostasis

Unlikely to match market leader's triple therapy


Proteostasis Therapeutics has suffered a major blow to its challenge to Vertex and its portfolio of cystic fibrosis medicines.

The company is attempting to seize some of the market share in cystic fibrosis (CF), a field which Vertex has carved out by developing a series of groundbreaking disease-modifying products, Kalydeco, Orkambi and Symkevi/Symdeko.

Vertex has a triple therapy in advanced development, and investors hoped that Proteostatis’ own combination could challenge Vertex.

However, yesterday Proteostasis unveiled disappointing phase 1 data for its triplet therapy for cystic fibrosis patients of PTI-801 (a CF transmembrane conductance regulator corrector), PTI-808 (CFTR potentiator) and PTI-428 (CFTR amplifier).

Y. Katherine Xu, an analyst at William Blair, says the results in relation to patients' lung function and other measures are disappointing, and doesn’t expect the company to match the high bar set by Vertex in its own triplet trials.

The underwhelming results from Proteostasis are further good news for Vertex, which saw AbbVie and Galapagos also post disappointing results for their triple therapy candidate.

This gives Vertex a clear run at being the first to market and best in class, with the triple therapy opening up 90% of the world’s CF population to treatment.

Vertex is running two parallel triplet studies, VX-659 + Symdeko and VX-445 + Symdeko, with one expected to emerge as superior, and be selected for filing.

One study was carried out in CF patients with one F508del mutation and one minimal function mutation, with a 14% improvement over placebo, while the other involved patients with two F508del mutations and showed a 10% improvement.

The chosen candidate is then expected to gain approval in the US market in the first half 2020, followed by Europe in the first half 2021.

In contrast, Proteostasis’ triplet therapy failed to show a significant improvement in the measure of patients' lung function referred to as ppFEV1.

The data also included readouts from separate studies of PTI-801 and PTI-428 as add-on treatments to Vertex’s Symdeko/Symkevi (tezacaftor/ivacaftor) therapy in patients with cystic fibrosis.

The news sent Proteostasis shares crashing down 63% yesterday - while analysts upgraded forecasts for Vertex’s own franchise.

Based in Boston, Mass like its bigger rival, Proteostasis plans to evaluate optimal doses of PTI-801 and PTI-808 as part of longer studies in cystic fibrosis patients who are not in the harder-to-treat group predisposed to rapid pulmonary decline.

This would match the exclusion criteria used in Vertex’s trials, but Y. Katherine Xu believes its chances of equalling its rival’s results are very slim.

William Blair says the news bolsters Vertex in a number of ways, and has remodelled its forecast accordingly. It is increasing its forecast peak market share of a Vertex triple reaching the market in the US and EU to 85% and 80%, up from 80% and 70%, respectively; and now predicts the company will be able to maintain its prices in both markets, rather than have to drop them slightly to see off competition.

Vertex and UK access row

The news of another failure for rivals to Vertex will come as a disappointment to healthcare payers in the US and Europe, which have hoped for competitors to help them drive the company’s prices down.

In the UK, Vertex has been at loggerheads with NHS England over access to dual therapy Orkambi, and the company’s chief executive Jeff Leiden appeared before the health select committee alongside his NHS counterparts to explain the three year impasse.

The chair of the health select committee Dr Sarah Wollaston MP wrote to the health secretary suggesting the government could refer Vertex to the Competition and Markets

Authority for “what appears to us to be the exploitation of a monopoly position in the supply of drugs for the treatment of cystic fibrosis”.

NHS England, NICE and Vertex have now resumed negotiations, and a deal struck in Scotland has added extra impetus to an agreement being reached in England.

Article by
Andrew McConaghie

26th March 2019

From: Research



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