REGENXBIO Announces Completion of Enrollment in Cohort 2 and Additional Positive Interim Data in AFFINITY DUCHENNE® Trial

Rhea-AI Summary

REGENXBIO Inc. (Nasdaq: RGNX) has completed enrollment in cohort 2 of the Phase I/II AFFINITY DUCHENNE trial of RGX-202, demonstrating strong microdystrophin expression across a wide range of patients. The third patient at dose level 1 showed the largest increase in microdystrophin expression at 83.4% of control. The company is on track to initiate a pivotal trial in the second half of 2024 and plans to discuss the new results in a conference call. Enrollment has been completed at dose level 2, and RGX-202 has been well tolerated with no drug-related serious adverse events in five patients. The company expects to make a pivotal dose determination in mid-2024 and share initial strength and functional assessment data for both dose levels. The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability, and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne.

Insights

Medical Research Analyst

REGENXBIO Inc.'s announcement on the completion of enrollment for cohort 2 of the Phase I/II AFFINITY DUCHENNE trial and the subsequent data on RGX-202 microdystrophin expression levels presents several significant points for analysis. Firstly, the reported 83.4% microdystrophin expression relative to control in a 6.6-year-old patient is a promising indicator of the therapeutic's potential efficacy. This high level of expression, coupled with a 93% reduction in serum creatinine kinase (CK) levels, suggests a robust biological response to the treatment. CK levels are a critical biomarker for muscle injury and are typically elevated in Duchenne muscular dystrophy patients, indicating muscle degradation. A significant reduction in CK levels post-treatment could imply a reduction in muscle damage, which would be a substantial clinical improvement.

From a research perspective, the utilization of both western blot and liquid chromatography-mass spectrometry (LC-MS) methods for measuring microdystrophin levels adds credibility to the data due to methodological triangulation. The trial's design, which includes proactive immunosuppression to mitigate potential immunologic responses, reflects a thoughtful approach to addressing safety concerns. The expectation to use microdystrophin expression as a surrogate endpoint for a Biologics License Application (BLA) filing under the accelerated approval pathway could expedite the treatment's availability to patients, assuming continued positive results.

Financial Analyst

The strategic implications of REGENXBIO's progress in the AFFINITY DUCHENNE trial for investors are multifaceted. The company's ability to meet enrollment targets and report positive interim results can be seen as a positive indicator of management's execution capabilities and the potential of RGX-202 as a product candidate. These developments could impact REGENXBIO's stock valuation, as the market often responds to clinical trial milestones and efficacy data. The anticipation of a pivotal trial in the second half of 2024 and the discussion of a BLA filing using the accelerated approval pathway suggest a clear roadmap for RGX-202's clinical development and potential market entry.

However, investors should be cognizant of the inherent risks in biotech investing, especially at the clinical trial stage. While the data is encouraging, the sample size is relatively small and further data from larger cohorts will be necessary to confirm efficacy and safety. The market potential for Duchenne muscular dystrophy treatments is significant and if RGX-202 continues to demonstrate positive results, it could capture a substantial market share. The financial implications of successful commercialization could be considerable, given the high unmet need and the potential for premium pricing of novel gene therapies.

Biotech Industry Analyst

The gene therapy landscape for rare diseases such as Duchenne muscular dystrophy is rapidly evolving and REGENXBIO's RGX-202 represents a significant advancement within this space. The use of adeno-associated virus (AAV) vectors to deliver an optimized transgene for a novel microdystrophin is a cutting-edge approach, leveraging the latest developments in genetic medicine. The reported data indicates that RGX-202 could emerge as a competitive player in the Duchenne treatment market, which has historically been limited in terms of effective therapies.

The company's engagement with key opinion leaders and the Duchenne community in trial design demonstrates an understanding of the importance of stakeholder collaboration in rare disease drug development. The focus on specific DMD gene mutations and the selection of meaningful clinical endpoints, such as the North Star Ambulatory Assessment (NSAA), aligns with current industry norms for patient-centric drug development. The potential for RGX-202 to serve as a one-time treatment contrasts with existing therapies that often require ongoing administration, which could lead to a paradigm shift in patient care and market dynamics.

• Completed enrollment in cohort 2 of the Phase I/II AFFINITY DUCHENNE^® trial of RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin
• New three-month assessment in third patient at dose level 1 demonstrates largest increase in microdystrophin expression
  • Patient aged 6.6 years old had expression level at 83.4% of control
• On track to initiate pivotal trial in second half of 2024
• Company plans to discuss these new results as part of a full rare disease program update on its conference call today, Wednesday, February 7, 4:30 p.m. ET

ROCKVILLE, Md., Feb. 7, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced that enrollment has completed at dose level 2 and reported additional interim safety and efficacy in the Phase I/II AFFINITY DUCHENNE^® trial of RGX-202 in patients with Duchenne muscular dystrophy (Duchenne) ages 4 to11 years old.

"We are thrilled to see that RGX-202 is demonstrating strong microdystrophin expression across a wide range of patients," said Kenneth T. Mills, President and CEO, REGENXBIO. "RGX-202 microdystrophin is differentiated with important biology most similar to naturally occurring dystrophin that protects from the muscle degradation associated with Duchenne. All boys with Duchenne are in need of new treatment options that can meaningfully impact disease, and we are working with great urgency to accelerate RGX-202 as an option for them."

Safety Update
As of February 6, 2024, RGX-202 has been well tolerated with no drug-related serious adverse events in five patients, aged 4.4 to 12.1 at dose level 1 (1x10¹⁴ genome copies (GC)/kg body weight) and dose level 2 (2x10¹⁴ GC/kg body weight). Time of post-administration follow up ranges from approximately three weeks to over nine months. All patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol.

Biomarker Data
In new data from the third patient, aged 6.6 years, who received RGX-202 at dose level 1, RGX-202 microdystrophin expression was measured to be 83.4% compared to control at three months. A reduction from baseline in serum creatinine kinase (CK) levels of 93% was observed at ten weeks.

All three patients, at dose level 1, who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin and reduction from baseline in serum CK levels, supporting evidence of clinical improvement.

RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne. The mean (SD) RGX-202 microdsytrophin expression levels (change from baseline) at three months following RGX-202 administration were 44.4% (n=3, SD:36.5%). The patient data is presented below.

Patient	Age at Dosing (years)	Weight at Dosing (kg)	Western blot (Jess method), RGX-202 Microdystrophin (% Normal Control)	CK Levels, week 10 (% reduction from baseline)
1	4.4	17.8	38.8	-43
2	10.5	28.3	11.1	-44
3	6.6	26.8	83.4	-93

Clinical Program Updates
REGENXIO expects to make a pivotal dose determination in mid-2024. The Company also expects to share initial strength and functional assessment data for both dose levels and the initiation of a pivotal trial in the second half of 2024. The Company plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing using the accelerated approval pathway.

"On our call this afternoon, we look forward to discussing these new clinical results and also reaffirming our guidance for the submission of a BLA this year for RGX-121 for the treatment of MPS II. The exciting topline pivotal data supporting this submission will be released later this morning in conjunction with a presentation at the 20th Annual WORLDSymposium™," said Mills.

Conference Call Details
REGENXBIO will host a conference call Wednesday, February 7 at 4:30 p.m. ET. Listeners can register for the webcast via this link. Analysts wishing to participate in the question and answer session should use this link. A copy of the slides being presented will be available via the Company's investor website. Those who plan on participating are advised to join 15 minutes prior to the start time. A replay of the webcast will also be available via the Company's investor website approximately two hours after the call's conclusion.

AFFINITY DUCHENNE Trial Design
The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with doses of 1x10¹⁴ GC/kg body weight (n=2) and 2x10¹⁴ GC/kg body weight (n=2). After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for additional patients to be enrolled.

The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests.

About RGX-202
RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12).

About Duchenne Muscular Dystrophy
Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.

About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8 and AAV9. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a "5x'25" strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025.

FORWARD-LOOKING STATEMENTS
This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations, clinical trials, costs and cash flow. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. Refer to the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of REGENXBIO's Annual Report on Form 10-K for the year ended December 31, 2022, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the U.S. Securities and Exchange Commission (SEC) and are available on the SEC's website at WWW.SEC.GOV. All of the forward-looking statements made in this press release are expressly qualified by the cautionary statements contained or referred to herein. The actual results or developments anticipated may not be realized or, even if substantially realized, they may not have the expected consequences to or effects on REGENXBIO or its businesses or operations. Such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Readers are cautioned not to rely too heavily on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this press release. Except as required by law, REGENXBIO does not undertake any obligation, and specifically declines any obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts:
Dana Cormack
Corporate Communications
dcormack@regenxbio.com 

Investors:
Chris Brinzey
ICR Westwicke
339-970-2843
chris.brinzey@westwicke.com 

 

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SOURCE REGENXBIO Inc.

FAQ

What is the ticker symbol for REGENXBIO Inc.?

The ticker symbol for REGENXBIO Inc. is RGNX.

What is the Phase I/II AFFINITY DUCHENNE trial of RGX-202 about?

The Phase I/II AFFINITY DUCHENNE trial is a clinical study to evaluate the safety, tolerability, and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne.

What is the age range of patients in the Phase I/II AFFINITY DUCHENNE trial?

The age range of patients in the Phase I/II AFFINITY DUCHENNE trial is 4 to 11 years old.

What is the expected timeline for the initiation of a pivotal trial for RGX-202?

The company is on track to initiate a pivotal trial for RGX-202 in the second half of 2024.

What are the safety updates for RGX-202 in the Phase I/II AFFINITY DUCHENNE trial?

As of February 6, 2024, RGX-202 has been well tolerated with no drug-related serious adverse events in five patients, aged 4.4 to 12.1 at dose level 1 and dose level 2.

What are the biomarker data results from the Phase I/II AFFINITY DUCHENNE trial?

New data from the third patient, aged 6.6 years, who received RGX-202 at dose level 1, showed a microdystrophin expression of 83.4% compared to control at three months, with a 93% reduction from baseline in serum creatinine kinase (CK) levels at ten weeks.

What are the clinical program updates for RGX-202?

REGENXBIO expects to make a pivotal dose determination in mid-2024 and share initial strength and functional assessment data for both dose levels, with the initiation of a pivotal trial in the second half of 2024.

What is the design of the Phase I/II AFFINITY DUCHENNE trial?

The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability, and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne.