The Vertex Advances program targeting alpha-1 antitrypsin deficiency

BOSTON–(BUSINESS WIRE)–Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the advancement of its research program targeting alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder characterized by a misfolding of proteins that can lead to liver disease and lungs.

Vertex announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for VX-634, allowing the company to initiate a first-in-man clinical trial for this concealer. of small molecule AAT in healthy volunteers. VX-634 is the first in a series of next-wave molecules under investigation with significantly improved potency and drug-like properties over previous Vertex AAT correctors, enabling the potential exploration of response to full dose.

Additionally, Vertex will initiate a 48-week Phase 2 study of VX-864, a first-generation AAT corrector, to assess the impact of longer-term treatment on polymer clearance by the liver, as well as the resulting functional AAT levels (fAAT) in plasma. The hypothesis that VX-864 can remove hepatic polymer stems from recently concluded exploratory analyzes of the initial 28-day Phase 2 study, which showed that VX-864 treatment reduced Z-polymer levels in the blood of patients with AATD by about 90% on average. % from baseline on Day 28 at the highest dose. The previous Phase 2 study of VX-864 showed that the corrector AAT was generally well tolerated and demonstrated evidence of mechanism, with increases in plasma fAAT over the 28-day study period. However, the magnitude of the treatment effect was insufficient to advance it to pivotal development. Additionally, the previous Phase 2 study did not address the effects of VX-864 therapy on hepatic polymer levels, an important clinical parameter. The current study is being conducted to determine if longer-term treatment with VX-864 will lead to clearance of hepatic polymers and, if so, whether longer-term treatment might also lead to greater increases in levels. plasma levels of fAAT.

“AATD is a serious disease aligned with our research and development strategy, and we remain committed to developing transformative small molecule medicines for patients with AATD to treat both the hepatic and pulmonary manifestations of this disease. disease,” said David Altshuler, MD, Ph.D., Executive Vice President, Global Research, and Chief Scientific Officer of Vertex. “By simultaneously advancing new, more potent molecules into the clinic and evaluating the impact of longer duration treatment, we hope to have both the assets and the data necessary to advance our AAT correction program in 2023.”

In line with its portfolio approach for all programs, Vertex is offering additional new wave AAT correctors, with the next molecules expected to enter the clinic starting in 2023.

About Alpha-1 Antitrypsin Deficiency

AATD is a rare genetic disorder characterized by a misfolding of proteins that can lead to liver and lung disease. AATD is caused by changes in the SERPINA1 gene that codes for the AAT protein. In the most common form of AATD, which occurs in people with the PiZZ genotype, these changes SERPINA1 cause the body to produce a 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 continue unchecked and damage the lungs. Accumulation of faulty AAT in the liver can also lead to liver disease. There is currently no cure for AATD. Nor is there a treatment that targets the underlying protein folding defect that causes the disease.

About the VX-634

VX-634 is an experimental small molecule that promotes the correct folding of the Z-AAT protein and is being evaluated for the treatment of alpha-1 antitrypsin deficiency. VX22-634-001 is a Phase 1, first-in-man, single-dose and multiple-escalating-dose study of VX-634 in healthy participants. The key endpoints will be the safety, tolerability and pharmacokinetics of VX-634.

About the 48-Week Phase 2 Study of VX-864 in People with AATD

This is a 48-week, open-label, phase 2 study of the efficacy and safety of VX-864 in approximately 20 participants with AATD and the PiZZ genotype. All participants will receive 500 mg of VX-864 every 12 hours for 48 weeks and will undergo periodic clinical evaluations. Ten participants will undergo a liver biopsy before receiving VX-864 and will undergo a second liver biopsy at week 24 or week 48. The primary endpoint will be the mean change from baseline in blood levels of functional alpha-1 antitrypsin at week 48.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has several approved drugs that treat the underlying cause of cystic fibrosis (CF) – a rare and life-threatening genetic disease – and has several ongoing CF clinical and research programs. Beyond cystic fibrosis, Vertex has a strong portfolio of experimental small molecule, cellular and genetic therapies in other serious diseases where it has in-depth knowledge of the causal human biology, including sickle cell disease, beta-thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, alpha-1 antitrypsin deficiency, and Duchenne muscular dystrophy.

Founded in 1989 in Cambridge, Mass., Vertex’s global headquarters are now located in Boston’s Innovation District and its international headquarters are in London. Additionally, the company has research and development sites and sales offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the best places to work in the industry, including 12 consecutive years Science the magazine’s list of Top Employers and one of Seramount’s 2022 Top 100 Companies. For company updates and to learn more about Vertex’s innovation history, visit or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

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, statements made by Dr. David Altshuler in this press release and statements regarding expectations regarding the clinical trial of VX-634, including trial design and potential benefits of VX-634, plans to initiate a Phase 2 study of VX-864, including timing of initiation and design of the study, expectations and potential benefits of VX-864, and expectations that the next AATD molecules will enter the clinic beginning in 2023. While Vertex believes the forward-looking statements contained in this release statements 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. These risks and uncertainties include, among others, that data from a limited number of patients may not be indicative of the final results of clinical trials, that trials may not be initiated or completed within the expected timeframe, or at all, that data from the Company’s development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, and other risks listed under “Risk Factors” in Vertex’s most recent annual report filed with the Securities and Exchange Commission (SEC) and available on the company’s website at and on the SEC website at You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.


Ryan H. Bowman