Avidity Biosciences (Nasdaq: RNA) opens access to del-zota in DMD44 as BLA filing nears

Avidity Biosciences, Inc. (Nasdaq: RNA) has officially launched a U.S. Managed Access Program for its investigational therapy delpacibart zotadirsen, also known as del-zota, targeting patients with Duchenne muscular dystrophy (DMD) mutations amenable to exon 44 skipping. The announcement comes at a time when the exon 44 segment remains without an approved exon-skipping therapy, placing del-zota in a potentially first-in-class position. The program will allow eligible patients to receive treatment under an FDA-authorized expanded access protocol while Avidity Biosciences prepares to file a Biologics License Application in 2026.

Del-zota is a core asset within the company’s pipeline of Antibody Oligonucleotide Conjugates, or AOCs, a proprietary class of therapeutics that leverage monoclonal antibodies to deliver oligonucleotides to specific tissue types. For Duchenne patients with exon 44 mutations, this targeted delivery platform is designed to produce meaningful levels of dystrophin protein, which is critical to maintaining muscle integrity and slowing disease progression.

Avidity Biosciences stated that enrollment into the Managed Access Program will begin by the end of 2025. Participants currently enrolled in the open-label extension study of del-zota, known as EXPLORE44-OLE, will be eligible to transition into the MAP as they complete their two-year participation period. This transition pathway is intended to ensure continued access for clinical trial participants while building an infrastructure for broader compassionate use.

This announcement follows Avidity Biosciences’ October 2025 pre-BLA meeting with the U.S. Food and Drug Administration. The company has confirmed that it received alignment on key regulatory components necessary to pursue a 2026 BLA submission under the agency’s accelerated approval pathway. If approved, del-zota could become the first approved exon 44-targeted therapeutic for Duchenne muscular dystrophy in the United States.

How does del-zota work and what makes it different from previous exon-skipping drugs?

Del-zota is designed to deliver phosphorodiamidate morpholino oligomers directly to skeletal and cardiac muscle cells. These PMOs are chemically engineered to target exon 44 of the dystrophin gene, enabling the skipping of the mutated exon and restoring the gene’s ability to produce functional dystrophin protein. Dystrophin is essential for stabilizing muscle cells during contraction, and its absence leads to the progressive muscle degeneration seen in Duchenne muscular dystrophy.

What differentiates del-zota from earlier exon-skipping candidates such as eteplirsen or golodirsen is its delivery mechanism. Avidity Biosciences uses a monoclonal antibody that binds to transferrin receptor 1, which is highly expressed on muscle cells. This receptor-mediated delivery approach significantly improves drug uptake into target tissues. The Phase 1/2 EXPLORE44 study demonstrated that del-zota achieved what the company described as “unprecedented” levels of PMO uptake in skeletal muscle, coupled with robust increases in dystrophin protein production and exon 44 skipping efficiency.

Biomarker results from EXPLORE44 included sustained reductions in creatine kinase levels, often approaching normal ranges. Creatine kinase is a marker of muscle damage and inflammation, and its decline suggests a potential stabilization of disease. Importantly, these biochemical improvements were accompanied by clinically observable functional gains in key assessments such as the Time to Rise from Floor test, the Four-Stair Climb, the Performance of Upper Limb measure, and the 10-Meter Walk/Run Test. These tests are commonly used in Duchenne clinical trials to evaluate gross motor function and disease progression.

What does the long-term safety profile of del-zota look like?

The ongoing EXPLORE44-OLE extension study has continued to assess the safety and tolerability of del-zota in a broader and more extended treatment population. According to Avidity Biosciences, del-zota has maintained a favorable safety profile over the long term. Most treatment-emergent adverse events were classified as mild or moderate. The most commonly reported side effects included upper respiratory tract symptoms, diarrhea, falls, back pain, and headache.

Only one participant discontinued from the trial due to a hypersensitivity event. Importantly, no new safety signals have emerged during the extension period, bolstering confidence in del-zota’s suitability for chronic use. These findings have likely contributed to the U.S. Food and Drug Administration granting del-zota several expedited development designations, including Rare Pediatric Disease, Orphan Drug, Fast Track, and Breakthrough Therapy designations. The European Medicines Agency has also granted del-zota Orphan designation, signaling broad regulatory interest in advancing this therapy.

How does the Managed Access Program support commercialization goals ahead of the BLA filing?

The launch of the Managed Access Program gives Avidity Biosciences a critical interim step between clinical trials and commercial availability. MAPs are designed to provide patients with serious or life-threatening diseases access to investigational therapies when no other options are available. In this case, the program specifically targets a subset of Duchenne patients who have no approved exon-skipping drugs tailored to exon 44.

By coordinating with participating healthcare providers and institutional review boards, Avidity Biosciences is creating the infrastructure necessary to collect real-world data, refine distribution logistics, and prepare for a commercial rollout following potential FDA approval. The company emphasized that patients transitioning from the EXPLORE44-OLE study will be among the first to benefit from this program, helping to preserve treatment continuity and accelerate physician familiarity with the therapeutic.

Moreover, the MAP serves as a strong signal to patient advocacy groups, regulatory stakeholders, and potential commercial partners that Avidity Biosciences is proactively addressing unmet needs ahead of formal market entry. With a BLA submission planned for 2026 and fast-track review status in place, the Managed Access Program could play a pivotal role in establishing market readiness and demonstrating demand for del-zota in the exon 44 Duchenne segment.

What does the Novartis acquisition mean for Avidity Biosciences and the future of del-zota?

The Managed Access Program announcement comes less than a month after Avidity Biosciences disclosed a $12 billion definitive merger agreement with Novartis AG. Under the terms of the deal, shareholders of Avidity Biosciences will receive USD 72.00 per share in cash, a 46 percent premium over the stock’s October 24, 2025 closing price of USD 49.15. The deal values Avidity Biosciences at approximately USD 12.0 billion on a fully diluted basis and includes additional consideration linked to the spinoff of its precision cardiology programs into a new company known as SpinCo.

Kathleen Gallagher, currently serving as chief program officer at Avidity Biosciences, will lead SpinCo as chief executive officer. Sarah Boyce, the current president and chief executive officer of Avidity Biosciences, will serve as chair of the board of the new entity.

For investors and biotech analysts, the Novartis acquisition is widely viewed as a strong endorsement of Avidity Biosciences’ AOC platform and a clear signal that the multinational pharmaceutical firm is investing heavily in next-generation RNA therapies. The del-zota program is expected to be a core component of Novartis’ neuromuscular disease strategy, particularly as the drug advances toward potential commercialization.

What are analysts and institutional investors tracking as del-zota moves closer to FDA submission?

Institutional interest in Avidity Biosciences has increased since the acquisition was announced. Analysts covering the stock believe del-zota represents one of the most clinically meaningful exon-skipping therapies currently in development and could become a blueprint for future RNA delivery strategies. The strength of the EXPLORE44 data package, including both biomarker and functional outcomes, sets a high bar for future approvals in this space.

Going forward, investors will focus on key milestones such as the pace of MAP enrollment, data updates from the EXPLORE44-OLE study, and the timing of the 2026 BLA submission. Analysts will also evaluate how Novartis integrates Avidity Biosciences’ broader pipeline, particularly its programs in myotonic dystrophy and facioscapulohumeral muscular dystrophy, both of which have shown preclinical promise.

The stock’s movement following the Novartis announcement underscores the bullish sentiment. Avidity Biosciences’ shares jumped significantly, reflecting confidence in both the value of the del-zota program and the underlying AOC technology. With regulatory momentum, strong clinical data, and corporate backing now aligned, del-zota appears well positioned to reshape the therapeutic landscape for exon 44 DMD patients.

Key takeaways: Avidity Biosciences expands access to del-zota ahead of 2026 BLA submission

• Avidity Biosciences, Inc. (Nasdaq: RNA) has launched a U.S. Managed Access Program (MAP) for delpacibart zotadirsen (del-zota), targeting patients with Duchenne muscular dystrophy mutations amenable to exon 44 skipping.

• The MAP will provide treatment access under an FDA-authorized protocol, with enrollment set to begin by the end of 2025. Patients completing the EXPLORE44-OLE extension trial will be eligible for transition into the program.

• Del-zota uses Antibody Oligonucleotide Conjugate (AOC) technology to deliver PMOs directly to muscle tissue, enabling exon 44 skipping and dystrophin protein restoration.

• Clinical data from the EXPLORE44 study showed unprecedented PMO delivery, robust dystrophin production, near-normal creatine kinase levels, and functional improvements in key motor endpoints.

• Long-term safety data from the EXPLORE44-OLE trial support continued use, with most adverse events reported as mild or moderate. Only one discontinuation due to hypersensitivity occurred.

• Del-zota holds FDA Fast Track, Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations, along with Orphan status from the European Medicines Agency.

• The company plans to submit a Biologics License Application (BLA) to the FDA in 2026 for accelerated approval, following alignment during a pre-BLA meeting in October 2025.

• The MAP serves as a critical step in building real-world treatment infrastructure and physician engagement ahead of potential commercial launch.

• Avidity Biosciences is being acquired by Novartis AG in a $12 billion deal, which includes the separation of early-stage cardiology programs into a new entity, SpinCo.

• Institutional investors and analysts are tracking MAP uptake, regulatory milestones, and further data from the del-zota program as key indicators of future success.