CAMBRIDGE, Mass. (
two-drug therapy significantly improved lung function in patients with the most common genetic mutation causing cystic fibrosis, according to final results from a mid-stage study announced Thursday.
The new data on the combination of Vertex's experimental VX-809 and currently marketed Kalydeco are culled from all 109 cystic fibrosis patients in the phase II study and build upon
released in May.
Based on these results, a pivotal phase III study utilizing the highest, 600 mg dose of VX-809 and Kalydeco in cystic fibrosis patients with two copies (homozygous) of the F508del gene will begin in early 2013, Vertex said.
Vertex also said it would conduct "additional studies" of the VX-809-Kalydeco combination therapy in cystic fibrosis patients with a single copy (heterozygous) of the F508del gene based on improvements in lung function seen in the phase II study.
Vertex shares are up 65% since the interim results from the VX-809-Kalydeco study were announced, in large part because projected peak sales from the company's cystic fibrosis drug business could reach $4-6 billion. Vertex closed Wednesday at $61.11.
From the start of the study through day 56, patients treated with high dose (600 mg) of VX-809 and Kalydeco experienced a 6.7% improvement in lung function compared to placebo and a 3.4% improvement within the drug treatment group. Both results were statistically significant.
Over the same time period, placebo-treated patients saw their lung function fall by 3.3%.
, which encompassed half the patients in the VX-809-Kalydeco study, the placebo-adjusted and within-group improvements in lung function were 8.6% and 4%, respectively. These interim results combined patients treated with three different doses of VX-809.
Vertex did not disclose final lung function results from the phase II study Thursday for all patients across the three different doses of VX-809. The company did say that patients treated with the low- and mid-doses of VX-809 plus Kalydeco also experienced statistically significant improvements in lung function compared to placebo although the improvements were lower than what was seen with the highest dose of VX-809.
Lung function was assessed by FEV1, which measures the amount of air a patient can forcibly exhale in one second. FEV1 is the measure of clinical benefit accepted by FDA and European regulators for the approval of new cystic fibrosis drugs.
Cystic fibrosis is a progressive disease that causes patients to typically lose about 1-2% of their lung function each year. Yet in Vertex's phase II study, the loss of lung function was accelerated in all patients in the first stage of the study.
From the start of the study through day 28, placebo patients lost almost 1% of their lung function but patients treated with high dose VX-809 alone lost almost 3% of their lung function in the same time period. In other words, VX-809-treated patients were faring worse than placebo.
In the second 28-day stage of the study, the lung function of placebo patients deteriorated by a further 2.5% but patients treated with Kalydeco added to high dose VX-809 rebounded dramatically with an improvement in lung function of 6.1%.
Further evidence supporting the synergistic benefit of combining high dose VX-809 and Kalydeco was seen in the study's responder analysis. In the first 28 days of the study, 10% of cystic fibrosis patients treated with the high dose of VX-809 experienced an improvement in lung function of 5% or more. But when Kalydeco was added to VX-809 in the second 28 days of the study, the percentage of 5% or greater lung function improvers grew to 55%.
Likewise, 5% of high dose VX-809 patients recorded a 10% improvement in lung function during the study's first stage, increasing to 25% when Kalydeco was added to VX-809 in the study's second stage.
Vertex did not disclose responder analyses for patients treated with low- and mid-dose VX-809 plus Kalydeco.
Wall Street expectations for the final results from the phase II study of VX-809 and Kalydeco appear to be largely met, based on a survey of institutional investors recently conducted by ISI Group bio-pharma analyst Mark Schoenebaum.
The 119 investors surveyed, on average, expected to see a 6.7% improvement in placebo-adjusted lung function from the high dose VX-809 arm of the study. This is precisely what Vertex delivered.
Combining the pooled drug arms of the study, investors polled by Schoenebaum were looking for a 6.1% improvement in lung function, adjusted for placebo. Vertex did not provide the actual result Thursday.
Vertex stands to grow its nascent cystic fibrosis business substantially if a VX-809-Kalydeco combination therapy is ultimately approved since about half of the 70,000 cystic fibrosis patients worldwide carry two copies of the F508del gene. Kalydeco was approved in January as a single-drug therapy for about 4% of cystic fibrosis patients carrying the G551D genetic mutation. First-quarter Kalydeco sales totaled $18.4 million.
Cystic fibrosis is caused by genetic mutations that result in a malfunctioning or missing protein known as CFTR required for the regulation of sweat production, mucus and certain aspects of digestion. Defective or missing CFTR proteins in lung cells results in the formation of thick, sticky mucus that leads to restricted airflow, chronic infections and lung damage.
Patients with the most common F508del mutation have missing or insufficient CFTR protein on the surface of cells. VX-809 is designed as a "corrector" drug that increases the amount of CFTR protein on the cell surface. Kalydeco, on the other hand, is a "potentiator" designed to improve the function of the damaged CFTR proteins.
Kalydeco was approved in January for cystic fibrosis patients with the G551D mutation. These patients have sufficient CFTR proteins on the surface of cells but the proteins are damaged and don't work correctly.
The phase II combination study treated cystic fibrosis patients with the F508del mutation with four weeks of VX-809 alone to increase the amount of CFTR protein, followed by another four weeks of VX-809 combined with Kalydeco to improve the function of the new CFTR protein. Three doses of VX-809 were studied along with a higher dose of Kalydeco.
--Written by Adam Feuerstein in Boston.
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