Avidity Biosciences Announces Positive AOC 1044 Data Demonstrated Significant Increase of 25% in Dystrophin Production and Reduction of Creatine Kinase Levels to Near Normal in People Living with Duchenne Muscular Dystrophy Amenable to Exon 44 Skipping in the Phase 1/2 EXPLORE44™ Trial
Avidity Biosciences (Nasdaq: RNA) announced positive results for delpacibart zotadirsen (AOC 1044) in the Phase 1/2 EXPLORE44™ trial for Duchenne muscular dystrophy (DMD44). The drug demonstrated:
- Unsurpassed muscle concentrations of PMO at 200 nM after three 5 mg/kg doses
- 37% increase in exon 44 skipping, up to 66% with 5 mg/kg dose
- 25% increase in dystrophin production, restoring up to 54% of normal levels
- Over 80% reduction in creatine kinase levels
- Favorable safety and tolerability profile
These results suggest potential for changing the treatment paradigm for DMD44 patients. The company plans to expedite the regulatory path for delpacibart zotadirsen and advance additional exon-skipping DMD candidates.
Avidity Biosciences (Nasdaq: RNA) ha annunciato risultati positivi per delpacibart zotadirsen (AOC 1044) nel trial di Fase 1/2 EXPLORE44™ per la distrofia muscolare di Duchenne (DMD44). Il farmaco ha dimostrato:
- Concentrazioni muscolari di PMO senza precedenti a 200 nM dopo tre dosi di 5 mg/kg
- Aumento del 37% nel salto dell'esone 44, fino al 66% con la dose di 5 mg/kg
- Aumento del 25% nella produzione di distrofina, ripristinando fino al 54% dei livelli normali
- Riduzione superiore all'80% dei livelli di creatina chinasi
- Profilo di sicurezza e tollerabilità favorevoli
Questi risultati suggeriscono un potenziale cambiamento nel paradigma di trattamento per i pazienti con DMD44. L'azienda prevede di accelerare il percorso normativo per delpacibart zotadirsen e promuovere ulteriori candidati per il salto dell'esone nella DMD.
Avidity Biosciences (Nasdaq: RNA) anunció resultados positivos para delpacibart zotadirsen (AOC 1044) en el ensayo de Fase 1/2 EXPLORE44™ para la distrofia muscular de Duchenne (DMD44). El fármaco mostró:
- Concentraciones musculares sin precedentes de PMO a 200 nM después de tres dosis de 5 mg/kg
- Aumento del 37% en el salto del exón 44, hasta el 66% con la dosis de 5 mg/kg
- Aumento del 25% en la producción de distrofina, restaurando hasta el 54% de los niveles normales
- Reducción de más del 80% en los niveles de creatina quinasa
- Perfil de seguridad y tolerabilidad favorable
Estos resultados sugieren un potencial para cambiar el paradigma de tratamiento para los pacientes con DMD44. La empresa planea acelerar el camino regulatorio para delpacibart zotadirsen y avanzar con otros candidatos de salto de exón para la DMD.
Avidity Biosciences (Nasdaq: RNA)는 듀헨 근육 위축증(DMD44)을 위한 제1/2상 EXPLORE44™ 시험에서 delpacibart zotadirsen (AOC 1044)의 긍정적인 결과를 발표했습니다. 이 약물은 다음을 보여주었습니다:
- 3회 5 mg/kg 투여 후 200 nM에서 PMO의 뛰어난 근육 농도
- 44번 엑손 삭제에서 37% 증가, 5 mg/kg 용량에서 최대 66%
- 디스트로핀 생산 25% 증가, 정상 수준의 최대 54% 회복
- 크레아틴 키나아제 수치 80% 이상 감소
- 유리한 안전성 및 내약성 프로파일
이 결과는 DMD44 환자에 대한 치료 패러다임의 변화를 제안합니다. 회사는 delpacibart zotadirsen의 규제 경로를 신속하게 진행하고 추가적인 엑손 삭제 DMD 후보를 발전시킬 계획입니다.
Avidity Biosciences (Nasdaq: RNA) a annoncé des résultats positifs pour delpacibart zotadirsen (AOC 1044) dans l'essai de phase 1/2 EXPLORE44™ pour la dystrophie musculaire de Duchenne (DMD44). Le médicament a démontré :
- Des concentrations musculaires inégalées de PMO à 200 nM après trois doses de 5 mg/kg
- Une augmentation de 37 % dans le saut de l'exon 44, jusqu'à 66 % avec une dose de 5 mg/kg
- Une augmentation de 25 % dans la production de dystrophine, restaurant jusqu'à 54 % des niveaux normaux
- Une réduction de plus de 80 % des niveaux de créatine kinase
- Un profil de sécurité et de tolérabilité favorable
Ces résultats suggèrent un potentiel pour changer le paradigme de traitement des patients DMD44. L'entreprise prévoit d'accélérer le processus réglementaire pour delpacibart zotadirsen et de faire avancer d'autres candidats au saut d'exon pour la DMD.
Avidity Biosciences (Nasdaq: RNA) hat positive Ergebnisse für delpacibart zotadirsen (AOC 1044) in der Phase 1/2 EXPLORE44™-Studie zur Duchenne-Muskeldystrophie (DMD44) bekannt gegeben. Das Medikament zeigte:
- Unübertroffene Muskelkonzentrationen von PMO zu 200 nM nach drei Dosen von 5 mg/kg
- 37% Steigerung bei der Skipping von Exon 44, bis zu 66% bei einer Dosis von 5 mg/kg
- 25% Steigerung der Dystrophinproduktion, Wiederherstellung von bis zu 54% der normalen Werte
- Über 80% Reduktion der Kreatinkinase-Werte
- Positives Sicherheits- und Verträglichkeitsprofil
Diese Ergebnisse deuten auf das Potenzial hin, das Behandlungsschema für DMD44-Patienten zu verändern. Das Unternehmen plant, den regulatorischen Weg für delpacibart zotadirsen zu beschleunigen und weitere Kandidaten zur Exon-Skirping-Therapie voranzutreiben.
- Delpacibart zotadirsen achieved unsurpassed muscle concentrations of PMO at 200 nM
- Statistically significant 37% increase in exon 44 skipping, up to 66% with 5 mg/kg dose
- Statistically significant 25% increase in dystrophin production, restoring up to 54% of normal levels
- Over 80% reduction in creatine kinase levels, reaching near-normal levels
- Favorable safety and tolerability profile in Phase 1/2 EXPLORE44 trial
- None.
Insights
The data from the EXPLORE44™ trial for delpacibart zotadirsen (del-zota) in Duchenne muscular dystrophy (DMD) patients is highly promising. The 25% increase in dystrophin production and 37% increase in exon 44 skipping are significant improvements over existing treatments. Most notably, the reduction of creatine kinase levels by >80% to near-normal levels is unprecedented and suggests potential disease-modifying effects.
The 200 nM concentration of PMO in skeletal muscle after just three doses indicates excellent tissue penetration, addressing a key challenge in DMD therapeutics. However, long-term safety data and functional outcomes will be important to fully assess del-zota's efficacy. The favorable safety profile is encouraging, but larger patient cohorts and longer follow-up are needed to confirm these findings.
Avidity Biosciences' announcement is a significant positive for the company. The robust efficacy data for del-zota in DMD could potentially accelerate its path to market, given the FDA Fast Track designation. This could lead to earlier-than-expected revenue streams and market penetration.
The
However, it's important to consider that further clinical trials and regulatory hurdles remain. The company's cash position and burn rate should be monitored closely as it progresses towards potential commercialization.
Avidity's Antibody Oligonucleotide Conjugate (AOC) technology demonstrates a significant leap in oligonucleotide delivery to muscle tissue. The 200 nM PMO concentration achieved in skeletal muscle is a major breakthrough, potentially solving the long-standing challenge of efficient drug delivery in DMD treatment.
The 66% exon skipping and 54% of normal total dystrophin levels observed in some patients are approaching thresholds that could translate to meaningful clinical benefits. This efficacy, combined with the dramatic reduction in creatine kinase, suggests that del-zota may not only slow disease progression but potentially stabilize or improve muscle function.
If these results are replicated in larger trials, Avidity's AOC platform could become a leading technology for treating genetic muscle disorders, extending beyond DMD to other neuromuscular diseases. This could position Avidity as a major player in the rare disease therapeutics market.
Delpacibart zotadirsen (AOC 1044) delivered unsurpassed muscle concentrations of PMO of 200 nM after three doses of 5 mg/kg
Statistically significant
Statistically significant increase of
Creatine kinase levels reduced to near normal with greater than
Delpacibart zotadirsen data demonstrated favorable safety and tolerability
Volume 10 of virtual investor and analyst series today, Friday, Aug. 9 at 8:00 a.m. ET
"This is an exciting moment as these data suggest del-zota has the potential to change the treatment paradigm and course of disease for patients with Duchenne muscular dystrophy mutations amenable to exon 44 skipping. We have not seen this level of dystrophin production and reduction in creatine kinase with other PMO exon-skipping treatments," said Diana Castro, M.D., Board Certified Neurologist and Neuromuscular Physician, Founder and Director Neurology and Neuromuscular Care Center, Founder and Director Neurology Rare Disease Center and EXPLORE44 trial program investigator. "These del-zota data are very encouraging as children and adults living with Duchenne muscular dystrophy mutations amenable to exon 44 skipping are still in need of targeted treatment options to address this debilitating disease."
Del-zota is designed to deliver PMO to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production. Del-zota has been granted Orphan designation by the
"The robust exon skipping, significant dystrophin production, and profound reduction of creatine kinase reinforce our belief in the potential of del-zota to be an effective treatment for people living with DMD44. These data support expediting the regulatory path for del-zota as quickly as possible," said Sarah Boyce, president and chief executive officer. "Del-zota is the first AOC in development from our DMD franchise and with this data, we are also advancing additional exon-skipping DMD candidates."
This initial assessment from the randomized, double-blind, placebo-controlled Phase 1/2 EXPLORE44 trial of del-zota provides a look at the safety and tolerability for 25 participants across two dose levels (5 mg/kg and 10 mg/kg). For the four-month assessment in the 5 mg/kg cohort, participants received three doses of 5 mg/kg del-zota (PMO dose), or placebo every six weeks. Data on muscle delivery, exon skipping, dystrophin production and creatine kinase were assessed from 10 participants in the 5 mg/kg cohort.
In the Phase 1/2 EXPLORE44 study, del-zota demonstrated:
- Unsurpassed delivery of PMO of 200 nM in skeletal muscle
- Statistically significant
37% increase in exon 44 skipping and up to66% exon 44 skipping - Statistically significant increase of
25% of normal in dystrophin production and restored total dystrophin up to54% of normal - Reduction in creatine kinase levels to near normal with greater than
80% reduction compared to baseline - Favorable safety and tolerability with most treatment emergent adverse events (AEs) mild or moderate in participants with DMD44.
Video Webcast Information
The company is hosting Volume 10 of its investor and analyst event series on August 9, 2024, beginning at 8:00 a.m. ET to discuss the initial data from the EXPLORE44TM trial of del-zota in people living with DMD44. The virtual event will be available via a live video webcast and can be accessed here or from the "Events and Presentations" page in the "Investors" section of Avidity's website. A replay of the webcast will be archived on Avidity's website following the event.
The EXPLORE44™ Phase 1/2 Trial of AOC 1044
The EXPLORE44™ trial is a randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial to evaluate del-zota in healthy volunteers and participants with DMD mutations amenable to exon 44 skipping (DMD44). EXPLORE44 has completed enrollment and is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of del-zota administered intravenously. The EXPLORE44 trial is assessing exon skipping and dystrophin protein levels in participants with DMD44. Participants with DMD44 have the option to enroll into an open-label extension study, EXPLORE44-OLE. For more information about the EXPLORE44 trial, visit the EXPLORE44 study website or visit https://www.clinicaltrials.gov and search for NCT05670730.
About Duchenne muscular dystrophy (DMD)
Duchenne muscular dystrophy (DMD) causes a lack of functional dystrophin that leads to stress and tears of muscle cell membranes, resulting in muscle cell death and the progressive loss of muscle function. The dystrophin protein maintains the integrity of muscle fibers and acts as a shock absorber through its role as the foundation of a group of proteins that connects the inner and outer elements of muscle cells. People living with DMD suffer from progressive muscle weakness that typically starts at a very young age. Over time, people with Duchenne will develop problems walking and breathing, and eventually, the heart and respiratory muscles will stop working. Those living with the condition often require special aid and assistance throughout their lives and have significantly shortened life expectancy. While there are treatments approved to treat people with DMD, there remains a very high unmet need. DMD is a monogenic, X-linked, recessive disease that primarily affects males, with one in 3,500 to 5,000 boys born worldwide having Duchenne.
About Del-zota (AOC 1044)
Del-zota (AOC 1044) is designed to deliver phosphorodiamidate morpholino oligomers (PMOs) to skeletal muscle and heart tissue to specifically skip exon 44 of the dystrophin gene to enable dystrophin production in people living with Duchenne muscular dystrophy with mutations amenable to exon 44 skipping (DMD44). DMD is characterized by progressive muscle degeneration and weakness due to alterations of a protein called dystrophin that protects muscle cells from injury during contraction. Del-zota consists of a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44. In a preclinical model of DMD, a murine active AOC produced durable exon skipping and functional dystrophin protein in skeletal muscle and heart tissue following a single intravenous dose. Del-zota is currently in Phase 1/2 development as part of the EXPLORE44™ trial for the treatment of DMD mutations amenable to exon 44 skipping.
About Avidity
Avidity Biosciences, Inc.'s mission is to profoundly improve people's lives by delivering a new class of RNA therapeutics - Antibody Oligonucleotide Conjugates (AOCs™). Avidity is revolutionizing the field of RNA with its proprietary AOCs, which are designed to combine the specificity of monoclonal antibodies with the precision of oligonucleotide therapies to address targets and diseases previously unreachable with existing RNA therapies. Utilizing its proprietary AOC platform, Avidity demonstrated the first-ever successful targeted delivery of RNA into muscle and is leading the field with clinical development programs for three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through internal discovery efforts and key partnerships. Avidity is headquartered in San Diego, CA. For more information about our AOC platform, clinical development pipeline and people, please visit www.aviditybiosciences.com and engage with us on LinkedIn and X.
Forward-Looking Statements
Avidity cautions readers that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the characterization of safety, tolerability and efficacy data associated with del-zota from the Phase 1/2 EXPLORE44™ trial; the standards against which the del-zota data are being measured; the impact of such data on the advancement of del-zota; the plans and timing and advancement of the EXPLORE44 trial; the design and goals of the EXPLORE44 trial and individual cohorts therein; Avidity's DMD franchise; the potential of Avidity's product candidates to treat rare diseases and Avidity's efforts to bring them to people suffering from applicable diseases; and the potential of AOCs to target a range of different cells and tissues beyond the liver, and to treat cardiac and immunological diseases. This press release also contains estimates and other statistical data made by independent parties and by us. This data involves a number of assumptions and limitations, and the reader is cautioned not to give undue weight to such estimates.
The inclusion of forward-looking statements should not be regarded as a representation by Avidity that any of these plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Avidity's business and those beyond its control, including, without limitation: preliminary results of a clinical trial are not necessarily indicative of final results and additional data related to del-zota that continues to become available may be inconsistent with the data produced as of the date hereof, and further analysis of existing data and analysis of new data may lead to conclusions different from those established as of the date cutoff; unexpected adverse side effects to, or inadequate efficacy of, Avidity's product candidates that may delay or limit their development, regulatory approval and/or commercialization, or may result in additional clinical holds which may not be timely lifted, recalls or product liability claims; Avidity is early in its development efforts; Avidity's approach to the discovery and development of product candidates based on its AOC platform is unproven, and the company does not know whether it will be able to develop any products of commercial value; potential delays in the commencement, enrollment, data readouts and completion of preclinical studies or clinical trials; Avidity's dependence on third parties in connection with preclinical and clinical testing and product manufacturing; regulatory developments in
Investor Contact:
Mike MacLean
(619) 837-5014
investors@aviditybio.com
Media Contact:
Navjot Rai
(619) 837-5016
media@aviditybio.com
View original content to download multimedia:https://www.prnewswire.com/news-releases/avidity-biosciences-announces-positive-aoc-1044-data-demonstrated-significant-increase-of-25-in-dystrophin-production-and-reduction-of-creatine-kinase-levels-to-near-normal-in-people-living-with-duchenne-muscular-dystrophy-amenab-302218647.html
SOURCE Avidity Biosciences, Inc.
FAQ
What were the key results of the EXPLORE44 trial for delpacibart zotadirsen (RNA)?
How does delpacibart zotadirsen (RNA) work in treating Duchenne muscular dystrophy?
What regulatory designations has delpacibart zotadirsen (RNA) received?
What are Avidity Biosciences' (RNA) next steps for delpacibart zotadirsen?
