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Report: Vertex Overstated Cystic Fibrosis Drugs Benefit

(BuzzNewsTrends/flickr)
(BuzzNewsTrends/flickr)

The Boston Globe reports that Cambridge-based Vertex Pharmaceuticals overstated the benefits of a new drug combination to treat cystic fibrosis when it released interim clinical trial data earlier this month.

Rob Weisman writes:

Shares of Vertex Pharmaceuticals Inc. plunged more than 18 percent in the first hour of trading Tuesday after the company acknowledged interim clinical trial data it released earlier this month for an experimental drug combination treating cystic fibrosis was in error.

In a statement correcting its earlier report on an ongoing midterm study, Cambridge-based Vertex said the interim data — which sent Vertex’s stock up more than 55 percent on May 7 — showed relative improvements in breathing for patients taking the drug in a clinical trial, not absolute improvements as the company previously reported.

The error resulted from “a misinterpretation between Vertex and our outside statistical vendor” on the type of analysis performed in the trial, a company spokesman said.

Here's more detail from The Street:

Vertex Pharmaceuticals overstated the response to its two-drug cystic fibrosis therapy earlier this month due to a "misinterpretation" of interim data from a phase II study, the company acknowledged Tuesday.

Fewer cystic fibrosis patients in the study saw their lung function improve by more than 5% following treatment with VX-809 and Kalydeco than was previously disclosed, Vertex said...

Of the cystic fibrosis patients treated with the two-drug therapy, 35% experienced an absolute improvement in lung function of 5% or more, not the 46% of patients previously disclosed by Vertex in early May.

Likewise, only 19% of patients experienced an absolute improvement in lung function of at least 10%. That's corrected from May 7, when Vertex said 30% of patients saw this level of benefit.

Here's the statement on Vertex's website:

Vertex Corrects and Provides Additional Data from Recent Interim Analysis of Phase 2 Combination Study of VX-809 and KALYDECO™ (ivacaftor) in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
- Corrected Data: Responder analysis showed 35% of patients experienced an absolute improvement in lung function (FEV1) of at least 5 percentage points and 19% had at least a 10 percentage-point improvement when treated with VX-809 and KALYDECO -

- Additional Data: Patients treated with VX-809 and KALYDECO experienced an 8.5 percentage point mean absolute improvement in lung function compared to patients treated with placebo (p=0.002) -

- Vertex plans to start a pivotal study of this combination to treat the underlying cause of CF in adults with two copies of the F508del mutation, pending final data and discussions with regulatory agencies -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today a correction to the previously reported responder analysis, as well as additional data from, the recent interim analysis of an ongoing Phase 2 study of VX-809 and KALYDECO™ (ivacaftor) that showed significant improvements in lung function (forced expiratory volume in one second, FEV1) among adults with cystic fibrosis (CF) who have two copies (homozygous) of the most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, F508del. As previously announced, there was a statistically significant improvement in lung function (absolute change in percent predicted FEV1) across the combined treatment groups relative to baseline compared to placebo (p=0.002). Today's announcement provides a correction to the responder analysis (n=37) for the absolute improvement in lung function compared to baseline and, for the first time, provides the mean absolute improvement in lung function compared to placebo observed among patients who received VX-809 (200mg, 400mg, 600mg; QD) and KALYDECO (250mg; q12h). The data reported today and earlier this month are based on 37 patients who completed 56 days of treatment with VX-809 and KALYDECO and 11 patients with one or two copies of the F508del mutation who received placebo. Vertex will host a conference call for investors and media today, May 29, 2012 at 8:00 a.m. ET, to discuss the correction and additional data.

On May 7, 2012, the company announced that approximately 46 percent (17/37) of patients with two copies of the F508del mutation experienced an improvement in lung function (FEV1) of 5 percentage points or more and approximately 30 percent (11/37) experienced an improvement of 10 percentage points or more from baseline to Day 56 when treated with the combination of VX-809 and KALYDECO. These results were relative improvements, not absolute improvements as originally reported.

The actual absolute improvements in lung function for these patients are: approximately 35 percent (13/37) experienced an absolute improvement of 5 percentage points or more and approximately 19 percent (7/37) experienced an absolute improvement of 10 percentage points or more from baseline to Day 56. As previously announced, none of the patients treated with placebo (0/11) achieved a 5 percentage-point or more mean absolute improvement in lung function from baseline to Day 56.

Additional data from the interim analysis are provided today for people with two copies of the F508del mutation. A mean absolute improvement in lung function of 8.5 percentage points was observed among those who were treated with VX-809 and KALYDECO compared to placebo (p=0.002). In addition, the within-group mean absolute improvement from baseline to Day 56 was 4.0 percentage points (p=0.002) for patients treated with the combination. From baseline to Day 56, those treated with placebo experienced a mean absolute decrease in lung function of 4.6 percentage points (p=0.04).

These data are from a planned interim analysis that was conducted after approximately half of the patients completed 56 days of treatment. Evaluation of patients with one copy (heterozygous, n=21) of the F508del mutation is ongoing. All patients have now completed dosing. Analyses are ongoing and complete data, including statistical analyses for all patient groups, will be available mid-year. Vertex plans to start a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation, pending final study results and discussions with regulatory agencies.

Interim Lung Function Data
VX-809 alone (200mg, 400mg or 600mg; QD) for 28 days followed by the addition of KALYDECO (250mg, q12h) for 28 days (n=37) Placebo
(n=11)
Mean absolute change in FEV1 from baseline to Day 56 compared to placebo 8.5 (p=0.002) N/A
Mean absolute change in FEV1 from baseline to Day 56 for pooled treatment and placebo groups 4.0 (p=0.002) -4.6 (p=0.04)
≥ 5 percentage point absolute improvement from baseline to Day 56 35% (13/37) * 0%
≥ 10 percentage point absolute improvement from baseline to Day 56 19% (7/37) * 0%
* On May 7, 2012, Vertex announced that approximately 46 percent (17/37) experienced an improvement from baseline to Day 56 in lung function of 5 percentage points or more, and approximately 30 percent (11/37) experienced an improvement from baseline to Day 56 of 10 percentage points or more. These results were relative improvements, not absolute improvements as originally reported.

"The improvements in lung function seen to date in this study exceeded our expectations. We're continuing to move forward as quickly as possible toward a pivotal study of VX-809 and KALYDECO in people with two copies of the F508del mutation," said Chris Wright, M.D., Ph.D., Vertex's Senior Vice President, Global Medicines Development and Medical Affairs.

Safety results are the same as those announced on May 7, 2012 and include data from all patients who had started treatment prior to this interim analysis. VX-809 was generally well tolerated alone and in combination with KALYDECO. The most common adverse events were pulmonary in nature. Most adverse events were mild or moderate in severity and comparable between treatment and placebo groups. The rate of serious adverse events was similar between treatment and placebo groups.

About this Phase 2 Study

Data from the first part of this study were announced in 2011. The interim data announced this month are from the second part of the ongoing Phase 2 randomized, double-blind, placebo-controlled study. This part of the study enrolled 108 people with CF ages 18 and older with one or two copies of the F508del mutation who were divided into five treatment groups of approximately 20 patients each. Three groups of homozygous patients were randomized to receive VX-809 alone (200mg, 400mg or 600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. One group of heterozygous patients received VX-809 alone (600mg) for 28 days and then in combination with KALYDECO (250mg) for an additional 28 days. The improvements in lung function were primarily observed following the addition of KALYDECO from Day 28 and maintained through Day 56. The placebo group includes both homozygous and heterozygous patients.

Cystic fibrosis is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. Located at the surface of cells, CFTR proteins act as channels to regulate the flow of salt and water into and out of the cells. In people with the F508del mutation in the CFTR gene, little to no CFTR protein reaches the cell surface. As a result, thick, sticky mucus builds up and blocks the passages in many organs, leading to a variety of symptoms. In particular, mucus builds up and clogs the airways in the lungs, causing chronic lung infections and progressive lung damage. VX-809, known as a CFTR corrector, is believed to help CFTR proteins reach the cell surface. KALYDECO, known as a CFTR potentiator, keeps the CFTR protein channels open longer to increase the flow of salt and water into and out of the cell.

VX-809 and KALYDECO were discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

This program aired on May 29, 2012. The audio for this program is not available.

Rachel Zimmerman Twitter Health Reporter
Rachel Zimmerman previously reported on health and the intersection of health and business for Bostonomix.

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