REGENXBIO ANNOUNCES NEW POSITIVE DATA FROM AFFINITY DUCHENNE® TRIAL OF RGX-202
REGENXBIO (RGNX) announced positive interim data from the Phase I/II AFFINITY DUCHENNE® trial of RGX-202, a gene therapy for Duchenne muscular dystrophy. Key highlights include:
1. Robust microdystrophin expression observed in patients aged 5.8 and 8.5 years at 77.2% and 46.5% of control, respectively, at the pivotal dose.
2. Consistent high expression across all age groups supports plans for accelerated approval.
3. RGX-202 well-tolerated with no serious adverse events.
4. Meaningful increases in microdystrophin expression and reduction in serum creatinine kinase levels observed in all seven patients.
5. REGENXBIO plans to initiate pivotal trial in Q4 2024 and complete enrollment in dose level 2 expansion cohort in early Q3 2024.
REGENXBIO (RGNX) ha annunciato dati positivi preliminari dallo studio di Fase I/II AFFINITY DUCHENNE® di RGX-202, una terapia genica per la distrofia muscolare di Duchenne. Ecco i punti salienti:
1. Espressione robusta di microdistrofina osservata in pazienti di età compresa tra i 5,8 e gli 8,5 anni a livelli del 77,2% e 46,5% rispetto al controllo, rispettivamente, alla dose cruciale.
2. Espressione elevata e costante in tutti i gruppi di età a supporto dei piani per l'approvazione accelerata.
3. RGX-202 ben tollerato con assenza di eventi avversi gravi.
4. Aumenti significativi nell'espressione di microdistrofina e riduzione dei livelli di creatinina serica osservati in tutti e sette i pazienti.
5. REGENXBIO prevede di iniziare lo studio cruciale nel Q4 2024 e completare l'arruolamento nel gruppo di espansione al livello di dose 2 all'inizio del Q3 2024.
REGENXBIO (RGNX) anunció datos interinos positivos del ensayo de Fase I/II AFFINITY DUCHENNE® de RGX-202, una terapia génica para la distrofia muscular de Duchenne. Los puntos destacados incluyen:
1. Expresión robusta de microdistrofina observada en pacientes de 5,8 y 8,5 años con un 77,2% y un 46,5% del control, respectivamente, en la dosis clave.
2. Expresión alta y consistente en todos los grupos de edad apoya los planes para la aprobación acelerada.
3. RGX-202 bien tolerado con sin eventos adversos graves.
4. Aumentos significativos en la expresión de microdistrofina y reducción en los niveles de creatinina sérica observados en los siete pacientes.
5. REGENXBIO planea iniciar el ensayo clave en el Q4 de 2024 y completar la inscripción en el cohort expansion de nivel de dosis 2 a principios del Q3 de 2024.
REGENXBIO (RGNX)는 듀셋 증후군 치료를 위한 유전자 치료제 RGX-202의 I/II상 AFFINITY DUCHENNE® 시험에서 긍정적인 중간 데이터를 발표했습니다. 주요 내용은 다음과 같습니다:
1. 강력한 마이크로디스트로핀 발현이 각각 77.2% 및 46.5%의 대조군 수준에서 5.8세 및 8.5세 환자에게 관찰되었습니다.
2. 모든 연령대에서 일관된 높은 발현이 신속 승인을 위한 계획을 지원합니다.
3. RGX-202는 심각한 부작용이 없으며 잘 견딜 수 있습니다.
4. 모든 일곱 환자에서 마이크로디스트로핀 발현의 의미 있는 증가와 혈청 크레아틴 분해 효소 수치의 감소가 관찰되었습니다.
5. REGENXBIO는 2024년 4분기에 주요 시험을 시작할 계획이며 2024년 3분기 초에 2단계 확장 코호트의 등록을 완료할 계획입니다.
REGENXBIO (RGNX) a annoncé des données intermédiaires positives de l'essai de phase I/II AFFINITY DUCHENNE® concernant le RGX-202, une thérapie génique pour la dystrophie musculaire de Duchenne. Voici les points forts :
1. Expression robuste de microdystrophine observée chez des patients âgés de 5,8 et 8,5 ans à 77,2 % et 46,5 % par rapport au contrôle, respectivement, à la dose clé.
2. Expression élevée et constante dans tous les groupes d'âge soutenant les plans pour une approbation accélérée.
3. Le RGX-202 est bien toléré avec aucun événement indésirable grave.
4. Augmentations significatives de l'expression de microdystrophine et réduction des niveaux de créatine kinase sérique observées chez les sept patients.
5. REGENXBIO prévoit de débuter l'essai clé au T4 2024 et de terminer l'inscription dans la cohorte d'expansion au niveau de dose 2 début T3 2024.
REGENXBIO (RGNX) gab positive Zwischenstände aus der Phase I/II AFFINITY DUCHENNE®-Studie zu RGX-202 bekannt, einer Gentherapie für die Duchenne-Muskeldystrophie. Die wichtigsten Punkte sind:
1. Robuste Mikro-Dystrophin-Expression, die bei Patienten im Alter von 5,8 und 8,5 Jahren mit 77,2 % bzw. 46,5 % des Kontrolldurchschnitts in der entscheidenden Dosis beobachtet wurde.
2. Konsistente hohe Expression über alle Altersgruppen unterstützt die Pläne für die beschleunigte Zulassung.
3. RGX-202 war gut verträglich mit keiner schweren Nebenwirkung.
4. Bedeutende Zunahmen der Mikro-Dystrophin-Expression und Verringerungen der Serum-Kreatinkinasewerte wurden bei allen sieben Patienten beobachtet.
5. REGENXBIO plant, im 4. Quartal 2024 die entscheidende Studie zu beginnen und die Rekrutierung in der zweistufigen Erweiterungsgruppe zu Beginn des 3. Quartals 2024 abzuschließen.
- Robust microdystrophin expression observed in patients aged 5.8 and 8.5 years (77.2% and 46.5% of control)
- Consistent high expression across all age groups supports plans for accelerated approval
- RGX-202 well-tolerated with no serious adverse events reported
- Meaningful increases in microdystrophin expression and reduction in serum creatinine kinase levels in all seven patients
- Manufacturing capacity of up to 2,500 doses of RGX-202 per year
- Initiation of pivotal trial expected in Q4 2024
- None.
Insights
The new data from REGENXBIO's AFFINITY DUCHENNE® trial of RGX-202 for Duchenne muscular dystrophy (DMD) is highly encouraging. The robust microdystrophin expression levels observed, particularly in older patients, are noteworthy. Two patients aged 5.8 and 8.5 years showed expression levels of 77.2% and 46.5% of control, respectively, at the pivotal dose. These are among the highest levels reported in older ambulatory patients with DMD.
The consistency of high expression across all treated patients, regardless of age, is a strong positive signal. It's important to note that RGX-202 is unique in encoding the C-Terminal (CT) domain, which may offer additional benefits in muscle protection and repair. The reduction in serum creatinine kinase levels across all patients who completed three-month assessments further supports the potential clinical benefit.
However, we must consider that while these biomarker results are promising, functional data is still pending. The upcoming strength and functional assessment data, expected in the second half of 2024, will be important in determining the true clinical impact of RGX-202. The initiation of the pivotal trial in Q4 2024 suggests confidence in the data, but investors should wait for more comprehensive results before drawing definitive conclusions.
REGENXBIO's manufacturing capabilities for RGX-202 are a significant strength in their development program. The company's proprietary NAVXpress™ platform process, a suspension-based manufacturing method, has demonstrated scalability up to 2,000L with consistent yield and product purity. This is important for potential commercialization.
The REGENXBIO Manufacturing Innovation Center's capacity to produce up to 2,500 doses of RGX-202 per year is impressive. This level of production capability is essential for addressing the entire DMD market, which could be a key differentiator from competitors. The ability to manufacture at this scale while maintaining product quality is often a major hurdle in gene therapy development and REGENXBIO appears to have overcome this challenge.
However, investors should note that manufacturing capacity alone doesn't guarantee success. Regulatory approval, pricing strategies and market adoption will all play important roles in the commercial success of RGX-202. Additionally, as gene therapy manufacturing technologies continue to evolve rapidly, REGENXBIO will need to ensure their process remains competitive in terms of cost and efficiency.
The AFFINITY DUCHENNE trial design demonstrates REGENXBIO's thoughtful approach to gene therapy development for DMD. The inclusion of a comprehensive, short-term prophylactic immunosuppression regimen is a proactive measure to mitigate potential complement-mediated immunologic responses, which have been a concern in other gene therapy trials.
The trial's inclusion criteria, based on dystrophin gene mutation status (including DMD gene mutations in exons 18 and above), show a targeted approach that may help in patient selection and potentially in demonstrating efficacy. The range of endpoints, including safety, immunogenicity, pharmacodynamic and pharmacokinetic measures and functional assessments like the North Star Ambulatory Assessment (NSAA), provide a comprehensive evaluation of RGX-202's potential benefits.
The expansion of enrollment to include boys aged 1-3 is significant, as early intervention in DMD is thought to be important for maximizing therapeutic benefit. However, it's important to note that the trial is still in its early stages and the pivotal trial is not set to begin until Q4 2024. While the current data is promising, investors should be aware that there's still a long road ahead in terms of proving long-term safety and efficacy, as well as navigating the regulatory approval process.
- Robust microdystrophin expression observed in new data from pivotal dose
- Patients aged 5.8 and 8.5 years at dosing had expression levels at
77.2% and46.5% of control, respectively
- Patients aged 5.8 and 8.5 years at dosing had expression levels at
- Consistent high expression of microdystrophin across treated patients in all age groups continues to support plans for accelerated approval
- Expects to initiate pivotal trial in Q4 2024
RGX-202 is an investigational one-time AAV Therapeutic designed to deliver a novel microdystrophin gene that includes key regions of the naturally occurring dystrophin gene. RGX-202 is the only gene therapy approved or in development for Duchenne that encodes for the C-Terminal (CT) domain to produce a microdystrophin that is closer to naturally occurring dystrophin. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself.
"With today's new, positive data, we are seeing a clear dose response and consistent, robust microdystrophin expression levels across all treated patients in the AFFINITY DUCHENNE trial, and, notably, among the highest levels of microdystrophin expression reported in older ambulatory patients," said Curran M. Simpson, President and CEO, REGENXBIO. "This data continues to build on the totality of evidence supporting the potential for RGX-202 to be a differentiated, best-in-class treatment for Duchenne. RGX-202 is well positioned to be the next potential gene therapy approved for Duchenne, and, with our commercial-ready, suspension-based manufacturing platform process, we believe we have the capacity to serve the entire market."
"I remain encouraged by the biomarker data from the AFFINITY DUCHENNE trial of RGX-202 and am eagerly anticipating the initial functional data from this program," said Aravindhan Veerapandiyan, M.D., Arkansas Children's Hospital. "This update is also encouraging for the Duchenne community, which is exploring various treatment options that could influence disease progression."
Data Update
In patients aged 5.8 and 8.5 who received RGX-202 at dose level 2, RGX-202 microdystrophin expression was measured to be
As of July 8, 2024, RGX-202 has been well tolerated with no serious adverse events. All seven patients who completed three-month trial assessments indicate meaningful increases in expression of RGX-202 microdystrophin and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement.
Microdystrophin expression results to date by dose and age in the AFFINITY DUCHENNE trial are shown in the table below.
Age range at screening | Dose Level 1 % RGX-202 (n = 3) | Dose Level 2 (Pivotal Dose) % RGX-202 (n = 4) |
4 to 7 years | 38.8, 83.4 | 77.2 |
8 to 11 years | 11.1 | 20.9, 46.5, 75.7 |
Clinical Program Updates
RGX-202 in the AFFINITY DUCHENNE trial is manufactured at the REGENXBIO Manufacturing Innovation Center using the Company's proprietary, high-yielding NAVXpress™ platform process. This suspension-based manufacturing process has demonstrated scalability up to 2,000L with consistent yield and product purity and is suitable for product commercialization. The REGENXBIO Manufacturing Innovation Center has the capacity and yields to produce up to 2,500 doses of RGX-202 per year.
REGENXBIO expects to complete enrollment in the dose level 2 expansion cohort early in the third quarter of 2024 and has initiated enrollment in the cohort for boys aged 1-3. Initiation of the pivotal trial is expected in the fourth quarter of 2024.
REGENXBIO expects to share initial strength and functional assessment data for both dose levels of the AFFINITY DUCHENNE trial in the second half of 2024.
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 aged 1-11.
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 a next-generation investigational gene therapy designed for improved function and outcomes in Duchenne. RGX-202 is the only gene therapy approved or in late-stage development for Duchenne with a differentiated microdystrophin construct that encodes key regions of naturally occurring dystrophin, including the C-Terminal (CT) domain. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase protein translation 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 and a well-characterized muscle-specific promoter (Spc5-12). RGX-202 is manufactured using REGENXBIO's proprietary, high-yielding NAVXpress™ suspension-based platform process.
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. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO's AAV Therapeutic platform, including Novartis' ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit www.regenxbio.com.
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, regulatory plans, 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, 2023, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the
Zolgensma® is a registered trademark of Novartis Gene Therapies. All other trademarks referenced herein are registered trademarks of REGENXBIO.
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 are the key results from REGENXBIO's AFFINITY DUCHENNE trial for RGX-202?
When does REGENXBIO (RGNX) expect to initiate the pivotal trial for RGX-202?
What is the manufacturing capacity for RGX-202 at REGENXBIO's facility?
What distinguishes RGX-202 from other gene therapies for Duchenne muscular dystrophy?
