Vertex Advances Inaxaplin (VX-147) into Phase 3 Portion of Adaptive Phase 2/3 Clinical Trial for the Treatment of APOL1-Mediated Kidney Disease

Rhea-AI Summary

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced the advancement of inaxaplin (VX-147) into Phase 3 of the global Phase 2/3 pivotal clinical trial in APOL1-mediated kidney disease. The trial will compare a 45 mg once daily oral dose to placebo, focusing on kidney function and proteinuria. The study has expanded to include adolescents aged 10-17 years. Positive Phase 2a results showed a significant reduction in urine protein to creatinine ratio (UPCR). Inaxaplin aims to address the underlying cause of AMKD, potentially transforming patient care.

Insights

Medical Research Analyst

Vertex Pharmaceuticals' advancement of inaxaplin into Phase 3 trials is a pivotal moment for addressing APOL1-mediated kidney disease (AMKD). The inclusion of a pediatric demographic widens the potential market and patient base, which is notable given the rarity of the condition. The Rare Pediatric Disease Designation and Breakthrough Therapy Designation by the FDA, alongside the EMA's PRIME and Orphan Drug designations, suggest a streamlined regulatory path and potential market exclusivity benefits.

From a medical research perspective, the statistically significant reduction in urine protein to creatinine ratio (UPCR) is promising. It indicates that inaxaplin could be a transformative treatment for AMKD, a disease with limited therapeutic options. Long-term, this could lead to a paradigm shift in treatment standards and improve patient outcomes. However, the success of the Phase 3 trial is not guaranteed and the safety profile will be closely monitored, especially with the inclusion of a younger cohort.

Financial Analyst

Investors will closely monitor Vertex's progress given the potential financial implications of a successful new therapy for a rare disease. The Breakthrough Therapy Designation could lead to an accelerated approval process and earlier revenue generation. Moreover, inaxaplin's expansion into the pediatric population may increase the addressable market size, which is typically limited for rare diseases.

Short-term, the announcement could positively influence Vertex's stock as it demonstrates progress in the company's pipeline. However, investors should consider the risks associated with clinical trials, as any setbacks could impact the company's valuation. Long-term, if inaxaplin is approved, it could provide a significant new revenue stream for Vertex, especially with the additional market exclusivity that orphan drug status confers.

Pharmaceutical Market Analyst

The progression of inaxaplin into Phase 3 trials represents a strategic move in the niche market of rare kidney diseases. The drug's potential to address an unmet medical need in AMKD could position Vertex as a leader in this space. The market for AMKD treatments is currently underdeveloped, which means a successful drug could command premium pricing and benefit from high demand.

In terms of market dynamics, the Orphan Drug and Rare Pediatric Disease Designations could grant Vertex certain incentives, including tax credits, fee waivers and market exclusivity upon approval. These factors could significantly affect Vertex's market positioning and competitive edge. The expansion to include adolescents also indicates a long-term strategic vision to capture a broader patient population.

– 45 mg once daily oral dose selected for Phase 3 –

– Results support trial expansion to lower age group and study will now include adolescents ages 10-17 years –

– If positive, pre-planned interim analysis at Week 48 may serve as the basis for accelerated approval in the U.S. –

BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that inaxaplin (VX-147) has advanced into the Phase 3 portion of the global Phase 2/3 pivotal clinical trial in APOL1-mediated kidney disease (AMKD), where a 45 mg once daily oral dose will be compared to placebo, on top of standard of care. The clinical trial is designed to assess the impact of inaxaplin on kidney function and proteinuria for people living with proteinuric kidney disease mediated by two variants in the APOL1 gene, known as AMKD. In addition, the trial has been expanded to include adolescents with AMKD ages 10 to 17 years.

Previously reported Phase 2a proof-of-concept data demonstrated that inaxaplin led to a statistically significant and clinically meaningful mean reduction in the urine protein to creatinine ratio (UPCR) of 47.6% at 13 weeks of treatment compared to baseline, providing the first clinical evidence that an oral small molecule APOL1 inhibitor can decrease proteinuria in people with AMKD.

“Inaxaplin, a first-in-class molecule that addresses the underlying cause of APOL1-mediated kidney disease, has already shown impressive results in the Phase 2a proof-of-concept study,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Advancing this trial into Phase 3 and broadening the trial to include younger patients is a critical step forward in bringing this potential therapy to patients who are waiting.”

“AMKD is a rapidly progressing condition and often remains silent until the disease reaches an advanced stage. We have no approved disease-specific therapies for this truly devastating condition, and inaxaplin has the potential to transform the care of AMKD and significantly improve the lives of patients,” noted Glenn M. Chertow, M.D., M.P.H., Professor of Medicine, Stanford University School of Medicine, and Chair of Vertex’s APOL1 Program Steering Committee. “The kidney community is strongly encouraged by inaxaplin’s potential, which energizes those of us caring for patients with AMKD.”

An Independent Data Monitoring Committee (IDMC) reviewed blinded and unblinded Phase 2 safety and efficacy data from the Phase 2/3 pivotal trial, which evaluated two different doses of inaxaplin compared to placebo for 12 weeks of treatment in patients ages 18 to 65 years and recommended the selection of a single inaxaplin dose of 45 mg once daily in the Phase 3 portion of the Phase 2/3 study. The IDMC also recommended enrolling adolescents with AMKD ages 10 to 17 years in the Phase 3 portion of the study.

The U.S. Food and Drug Administration (FDA) has granted inaxaplin Rare Pediatric Disease Designation (RPD) and Breakthrough Therapy Designation (BTD) for APOL1-mediated focal segmental glomerulosclerosis (FSGS). The European Medicines Agency (EMA) has also granted inaxaplin Priority Medicines (PRIME) and Orphan Drug designations for AMKD.

About the Phase 2/3 AMPLITUDE Study

Inaxaplin is a potential first-in-class, investigational small molecule inhibitor of APOL1 with the goal of targeting the underlying cause of APOL1-mediated kidney disease (AMKD).

The primary efficacy endpoint for the final analysis is estimated glomerular filtration rate (eGFR) slope in patients receiving inaxaplin compared to placebo. The secondary efficacy endpoint is time to composite clinical outcome, which will also be assessed at the final analysis and is defined as a sustained decline of ≥30% from baseline in the eGFR, the onset of end-stage kidney disease or death. The final study analysis will occur when subjects have at least two years of eGFR data and when approximately 187 composite clinical outcomes have occurred.

The study is also designed to have a pre-planned interim analysis at Week 48 evaluating eGFR slope, supported by a percent change from baseline in proteinuria in the inaxaplin arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval of inaxaplin in the U.S. for patients with AMKD.

Enrollment in the study is ongoing, with more than 200 sites open in the U.S. and internationally.

About APOL1-Mediated Kidney Disease

APOL1-mediated kidney disease (AMKD) is a form of chronic kidney disease caused by variants in the APOL1 gene. Approximately 100,000 people in the U.S. and Europe have two APOL1 genetic variants and proteinuric kidney disease. People who inherit two variants in the APOL1 gene have a course of disease that is far more aggressive than in the absence of APOL1 genetic variants. Inherited APOL1 genetic variants may lead to kidney cell injury, cell death and damage to the glomeruli (which filter blood in the kidney). This leads to protein in the urine (known as “proteinuria”) and decreased ability of the kidney to function, which can lead to dialysis, transplant or death.

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 approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency.

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Carmen Bozic, M.D., and Glenn Chertow, M.D., M.P.H., in this press release, statements regarding Vertex’s plans for and study design of the Phase 3 portion of the clinical trial for inaxaplin, including the study’s expansion to include adolescents with AMKD, expectations that the pre-planned interim analysis at Week 48 may serve as the basis for Vertex to seek accelerated approval in the U.S., and our expectations for the benefits of inaxaplin. 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 factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's research and development programs may not support registration or further development of its compounds due to safety, efficacy, and other risks listed under the heading “Risk Factors” in Vertex's annual report and in subsequent filings filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com and www.sec.gov. 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)

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FAQ

What is the ticker symbol of Vertex Pharmaceuticals Incorporated?

The ticker symbol of Vertex Pharmaceuticals Incorporated is VRTX.

What is the focus of the Phase 3 trial for inaxaplin (VX-147)?

The Phase 3 trial will compare a 45 mg once daily oral dose of inaxaplin to placebo, assessing its impact on kidney function and proteinuria in APOL1-mediated kidney disease.

What did the Phase 2a results for inaxaplin show?

The Phase 2a results demonstrated a statistically significant and clinically meaningful reduction in the urine protein to creatinine ratio (UPCR) of 47.6% at 13 weeks of treatment compared to baseline.

What designations has inaxaplin received from regulatory bodies?

Inaxaplin has received Rare Pediatric Disease Designation (RPD) and Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for APOL1-mediated focal segmental glomerulosclerosis (FSGS). It has also received Priority Medicines (PRIME) and Orphan Drug designations from the European Medicines Agency (EMA) for AMKD.

Who recommended the selection of a 45 mg once daily dose for the Phase 3 trial?

An Independent Data Monitoring Committee (IDMC) recommended the selection of a 45 mg once daily dose for the Phase 3 trial based on safety and efficacy data from the Phase 2/3 pivotal trial.