Business Wire

Vertex Announces Primary Endpoint Achieved in Phase 2 Study of VX-864 in Alpha-1 Antitrypsin Deficiency

Share

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that in a Phase 2 proof-of-concept study, VX-864 achieved rapid, consistent and statistically significant increases in mean functional alpha-1 antitrypsin (fAAT) levels of 2.2 to 2.3 micromolar from baseline in people with alpha-1 antitrypsin deficiency (AATD) with the PiZZ genotype, across three dose groups of VX-864 compared to placebo. VX-864 was generally well tolerated in the Phase 2 study. These data provide clear evidence that an oral small molecule corrector designed to promote the proper folding of the mutant Z-AAT protein can increase plasma levels of fAAT in patients with AATD. Although results provide proof-of-mechanism, the magnitude of treatment effect observed in this study is unlikely to translate into substantial clinical benefit. As such, Vertex will not advance VX-864 into late-stage development and instead will advance additional novel small molecule correctors with the potential for increased clinical efficacy into the clinic.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210610005939/en/

To view this piece of content from mms.businesswire.com, please give your consent at the top of this page.

Figure 1: Statistically significant increase in mean functional and antigenic AAT observed at day 28 compared to placebo (Graphic: Business Wire)

“This is the first time that dosing of a small molecule corrector of the Z-AAT protein resulted in significant elevations in both functional and antigenic levels of AAT in people with AATD. We are encouraged by the clear separation of AAT levels in the VX-864 treated groups versus placebo and the favorable safety profile,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Based on these findings, we remain committed to developing transformative treatments for AATD and are working with urgency to translate the learnings from this study to optimize the next set of small molecule correctors so that we can fully realize the potential that this class of molecules may hold for people living with this disease.”

Efficacy Results

The study met its primary endpoint, with all VX-864 dose groups demonstrating highly statistically significant increases in plasma fAAT levels from baseline compared to placebo at day 28 of treatment. Treatment with VX-864 resulted in a mean increase of 2.2 to 2.3 micromolar in fAAT levels across the three dose groups studied compared to placebo. All dose groups showed a rapid increase in fAAT by day 7 which was sustained over 28 days of treatment. Similar statistically significant increases in antigenic AAT levels were observed compared to placebo, with a mean increase of 2.7 to 3.5 micromolar across the three dose groups studied. Plasma fAAT levels returned to baseline, in the 28-day safety follow-up period following VX-864 discontinuation, consistent with the half-life of native AAT protein and further confirming the biological activity of VX-864.

Safety Results

In this study, VX-864 was generally well tolerated. All but one patient completed treatment. There were no discontinuations due to adverse events (AEs) and there were no serious adverse events (SAEs) considered related to study drug. The majority of AEs were mild or moderate in severity and not treatment limiting. The most common AEs in VX-864 treated patients were diarrhea and nausea. Liver function test (LFT) results were similar between the placebo and VX-864 treated groups, and there was no evidence of any impact on LFT results with VX-864.

Next Steps

The results of the VX-864 study demonstrated proof-of-mechanism with a rapid, consistent and clear effect on functional and antigenic AAT levels and a safety profile consistent with no mechanism-related toxicity. The data collected are anticipated to enable optimization of Vertex’s small molecule corrector approach in AATD and the rapid progression of a portfolio of new molecules with the potential for greater clinical efficacy into the clinic in 2022. In addition, the learnings from the VX-864 study are expected to enable efficiencies in clinical trial design, enrollment and execution for future assets.

About the Phase 2 Study in People with AATD

The Phase 2 study was a randomized, double-blind, placebo-controlled study of the efficacy and safety of VX-864 in people with the PiZZ genotype. People were randomized to one of three dose groups of VX-864 or placebo for 28 days. In addition, there was a 28-day follow-up period after the last dose of treatment. The primary outcome measures were the mean change from baseline in plasma fAAT levels at day 28 compared to placebo as well as safety and tolerability of VX-864.

About Alpha-1 Antitrypsin Deficiency

AATD is a rare, genetic disease characterized by a protein folding defect which can lead to liver and lung disease. AATD is caused by changes in the SERPINA1 gene that encodes the AAT protein. In the most common form of AATD, which occurs in people with a PiZZ genotype, these changes to SERPINA1 cause the body to produce misfolded AAT protein that gets trapped inside the liver, where most AAT is made. This leads to low levels of AAT protein in the blood. Low blood levels of AAT can allow inflammation to proceed unchecked and damage the lungs. The accumulation of defective AAT in the liver can also lead to liver disease. There is currently no cure for AATD. There are also no treatments that target the underlying protein folding defect that is the cause of the disease.

Investor Webcast

The conference call will be webcast live, and a link to the webcast can be accessed on the Vertex website at www.vrtx.com in the “Investors” section. To access the call via phone, please dial (866) 501-1537 (U.S.) or +1 (720) 545-0001 (International). To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the companies’ website for approximately 30 days.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, (i) statements by Dr. Carmen Bozic in this press release, (ii) statements regarding the company’s plans to advance additional novel small molecule(s) for AATD into the clinic in 2022 and (iii) the statements set forth under the caption “Next Steps” in this press release. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, risks related to the company’s AATD research programs, that data from the company's research and development programs may not support registration or further development of its compounds due to safety, efficacy, or other reasons, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report filed with the Securities and Exchange Commission at www.sec.gov and available through the company's website at www.vrtx.com. You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

To view this piece of content from cts.businesswire.com, please give your consent at the top of this page.

Contact information

Vertex Pharmaceuticals Incorporated

Investors:
Michael Partridge, +1 617-341-6108
or
Brenda Eustace, +1 617-341-6187
or
Manisha Pai, +1 617-429-6891

Media:
mediainfo@vrtx.com
or
U.S.: +1 617-341-6992
or
Heather Nichols: +1 617-839-3607
or
International: +44 20 3204 5275

About Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.

Subscribe to releases from Business Wire

Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from Business Wire

DC Secretary Announces Annual Determinations Committees Outcome28.3.2024 21:14:00 CET | Press release

DC Administration Services, Inc. has today announced the composition of five regional Determinations Committees (DCs), effective from April 27, 2024. Voting Dealers (for all regions): Voting Non-Dealers (for all regions): Bank of America N.A. Citadel LLC Barclays Bank plc Elliott Management Corporation BNP Paribas Pacific Investment Management Company LLC Citibank, N.A. Deutsche Bank AG Goldman Sachs International JPMorgan Chase Bank, N.A. Voting Dealer for the Americas, EMEA, AEJ, and Japan Determination Committees: Mizuho Securities Co., Ltd. The process for selecting DC members is specified in the DC rules. The DC rules, along with more information about the Determinations Committees and what they do can be found at the Determinations Committees website: https://www.cdsdeterminationscommittees.org/. View source version on businesswire.com: https://www.businesswire.com/news/home/20240328441002/en/Contact information Press Inquiries: Orlando Figueroa orlando.figueroa@citadelspv.com

LambdaTest Launches The Phoenix Project, an Employee Resource Group for Women28.3.2024 16:00:00 CET | Press release

LambdaTest, a leading cloud-based unified testing platform, announced the launch of The Phoenix Project, an Employee Resource Group (ERG) dedicated to supporting and promoting the success of its female employees. “LambdaTest is committed to fostering a diverse, inclusive, and equitable workplace where all employees feel valued and empowered to reach their full potential,” said Chandini Chopra, VP of People and Culture at LambdaTest. “The Phoenix Project is a critical step towards achieving this goal by providing a platform for professional development, networking, and mentorship, especially for our women employees.” The Phoenix Project Aims To: Offer professional development workshops, networking opportunities, and dedicated time off for women to participate in ERG initiatives. Provide mentorship programs connecting senior female employees with mentees. Promote leadership development among women within the company. Create a sense of community for women in the workplace. Leadership and

The reopening of the Yokohama Museum of Art adds another innovative and distinctive venue for events in Yokohama28.3.2024 16:00:00 CET | Press release

After extensive renovations, the iconic Yokohama Museum of Art has reopened its doors to visitors from all over the world. The museum’s reopening paves the way to new and closer collaboration with international events in Yokohama. This extraordinary venue is the ideal setting for a one-of-a-kind gathering, in part, supported by the Yokohama Convention & Visitors Bureau (hereinafter YCVB). The Yokohama Museum of Art Founded in 1989, the Yokohama Museum of Art collects over 14,000 works of art that reflect the many facets of life in Yokohama—past, present, and future. The reopening of the museum coincides with the Yokohama Triennale, an international exhibition featuring contemporary artists whose decentralized exhibits turn the entire metropolis into an art museum. The 8th Yokohama Triennale is being held from March 15 to June 9, 2024, with the Yokohama Museum of Art being a pivotal venue for the exhibition. With the museum firmly back on the map as Yokohama’s leading artistic venue, YC

Eight new sustainability-themed experiences—exclusive to Yokohama—for convention participants28.3.2024 16:00:00 CET | Press release

In a survey conducted by Yokohama Convention & Visitors Bureau (hereinafter YCVB), many convention attendees expressed particular interest in Yokohama’s culture, sightseeing spots, and local cuisine. In response, YCVB has developed eight new Yokohama Tours for event attendees to enjoy during their free time in Yokohama, keeping in line with our ethos of sustainability. Noge Area Bar-Hopping Tour, complete with guide Known affectionately by locals as Yokohama’s kitchen, Noge is a bustling nightlife spot that is home to over 600 izakaya (Japanese-style pubs). A knowledgeable local guide will lead participants to all the hidden gems in Noge, where they can indulge in distinctive, delicious pub-style food and drink. With easy on-foot accessibility, participants can rest assured this fun night out won’t impact their carbon footprint. Soto Zen Tour of Sojiji, head temple of the Soto Zen school As a prominent Zen sect in Japan, Soto Zen provides one of the best Zen wellness experiences. Durin

Nordson EFD Releases New 3-Axis Automated Fluid Dispensing Systems28.3.2024 15:00:00 CET | Press release

Nordson EFD, a Nordson company (NASDAQ: NDSN) and leading precision fluid dispensing systems manufacturer is proud to announce the new GVPlus and PROX families of automated fluid dispensing products. Both robotic solutions share a focus on motion, workspace, repeatability, payload, setup, and vision technology enhancements. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240305726899/en/ The GV Series offers market-leading dimensional positional accuracy and deposit placement repeatability. (Photo: Business Wire) The new GVPlus automated fluid dispensing solution offers improved repeatability, bigger payloads with simplified setup requirements, and superior vision capabilities. Repeatability is now best-in-class at 8 μm, improving repeatability to ±0.008 mm. Setting up the robot is easier due to a new dual mounting flange that enables a tool payload of up to 4.5 kg (10 lbs). When paired with the working area of 400 mm x 400 m

HiddenA line styled icon from Orion Icon Library.Eye