The New England Journal of Medicine Publishes Results from Phase 1/2 MARINA® Trial of Delpacibart Etedesiran (del-desiran) for Treatment of Myotonic Dystrophy Type 1
Rhea-AI Summary
Avidity Biosciences (Nasdaq: RNA) announced Phase 1/2 MARINA results for delpacibart etedesiran (del-desiran) in myotonic dystrophy type 1 (DM1) published in The New England Journal of Medicine on Feb 19, 2026. Treated participants showed an average ~40% reduction in DMPK mRNA and improvements in splicing, myotonia, muscle strength, mobility, and patient-reported function. Del-desiran had an acceptable safety profile overall; two serious adverse events occurred, one deemed drug-related and one led to discontinuation. The 4 mg/kg dose is in the global Phase 3 HARBOR study; topline 54-week readout expected in H2 2026.
Positive
- Mean ~40% reduction in DMPK mRNA across treated participants
- Splicing improvements observed at 2 mg/kg and 4 mg/kg doses
- Improvements in functional measures: myotonia, strength, mobility, and DM1-Activ
- Phase 3 HARBOR fully enrolled; 54-week topline readout expected H2 2026
Negative
- Two serious adverse events occurred; one SAE was drug-related
- One participant discontinued in the 4 mg/kg cohort due to an SAE
Key Figures
Market Reality Check
Peers on Argus
RNA is essentially flat (-0.01%) while close peers show mixed moves, from -7.08% (MRUS) to +1.21% (CRSP, NUVL), indicating a stock-specific setup rather than a coordinated sector move.
Previous Clinical trial Reports
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Sep 10 | DMD44 Phase 1/2 data | Positive | -0.5% | Groundbreaking del-zota Phase 1/2 results with strong dystrophin and CK changes. |
| Jul 28 | DM1 Phase 3 enrolled | Positive | -4.7% | HARBOR Phase 3 enrollment completion and global marketing submission plans. |
| Jun 09 | FSHD FORTITUDE data | Positive | -9.9% | Positive FORTITUDE Phase 1/2 topline del-brax data with functional gains. |
| Jun 09 | FSHD AA pathway | Positive | -9.9% | FDA opens accelerated approval path and launch of FORWARD Phase 3 study. |
| Apr 08 | DM1 orphan Japan | Positive | -5.5% | Orphan Drug designation for del-desiran in Japan with supportive MARINA data. |
Clinical and regulatory milestones have historically been followed by negative price reactions, with same-tag events averaging -6.09% despite positive trial outcomes and designations.
Over the past year, Avidity has delivered a series of positive clinical milestones across its RNA therapeutic programs. For DM1, del-desiran secured multiple regulatory designations and advanced into the global Phase 3 HARBOR trial, with enrollment completed by mid-2025. For FSHD and DMD44, del-brax and del-zota showed strong functional and biomarker data and positioned for BLA filings. Yet prior clinical trial headlines, including the MARINA and FORTITUDE programs, were often followed by negative short-term price moves, framing today’s NEJM publication in that context.
Historical Comparison
Over the last five clinical trial updates, RNA’s average move was -6.09% despite positive data. Today’s NEJM MARINA publication fits the same category but has not triggered a similar negative reaction so far.
For DM1, del-desiran progressed from promising MARINA/MARINA-OLE data and multi-region designations to Japanese Orphan Drug status and full Phase 3 HARBOR enrollment. The NEJM Phase 1/2 MARINA publication adds peer-reviewed validation ahead of the planned HARBOR readout and subsequent marketing submissions.
Market Pulse Summary
This announcement details NEJM publication of Phase 1/2 MARINA results, with del-desiran achieving ~40% DMPK mRNA reduction, functional improvements and an acceptable safety profile in 38 DM1 participants. It reinforces the rationale for the ongoing Phase 3 HARBOR trial using the 4 mg/kg dose in patients aged 16+. In light of prior clinical milestones that sometimes coincided with negative moves, investors may focus on Phase 3 design, upcoming 54-week readout timing, and regulatory execution as key next checkpoints.
Key Terms
siRNA medical
antibody oligonucleotide conjugates medical
randomized, double-blind, placebo-controlled medical
myotonia medical
treatment emergent adverse events medical
serious AEs medical
AI-generated analysis. Not financial advice.
Del-desiran effectively delivered siRNA to muscle, resulting in approximately
Treatment demonstrated improvements in multiple measures including myotonia, muscle function and strength, mobility and patient-reported outcomes
Del-desiran showed acceptable safety and tolerability with most adverse events mild or moderate
DM1 is an underrecognized, progressive and often fatal neuromuscular disease with no disease modifying therapies. Del-desiran is an investigational treatment designed to address the underlying genetic root cause of DM1 by reducing total levels of the toxic, DMPK (myotonic dystrophy protein kinase) mRNA. The accumulation of these toxic mRNA sequester key RNA-regulatory proteins that subsequently lead to missplicing of several downstream genes, resulting in the diverse clinical manifestations of disease.
The Phase 1/2 MARINA trial was a randomized, double-blind, placebo-controlled study designed to evaluate the safety and tolerability of single and multiple ascending doses of del-desiran administered intravenously in adults with DM1 for six months. Data were assessed from 38 participants who were randomized 3:1 to receive one dose of 1 mg/kg del-desiran, three doses of either 2 mg/kg del-desiran or 4 mg/kg del-desiran (reflected as siRNA dose), or placebo. The primary endpoint of the study was to evaluate the safety and tolerability of del-desiran. Exploratory endpoints were to evaluate the clinical activity of del-desiran across multiple efficacy measures.
"These final results from the MARINA study further reinforce del-desiran data reported thus far showing acceptable safety profile and improvements across a range of key functional assessments including myotonia, a hallmark symptom of DM1," said Nicholas E. Johnson, M.D., M.Sci., FAAN, professor and vice chair of research in the Department of Neurology at
Results from the Phase 1/2 MARINA study of del-desiran published in NEJM demonstrated:
- Effective delivery of del-desiran (siRNA) to muscle, with a mean ~
40% reduction in DMPK mRNA across all treated participants. - Splicing improvements in a key set of muscle-specific genes following treatment with del-desiran 2 mg/kg and 4 mg/kg.
- Improvements in exploratory functional measures including:
- Hand function/myotonia (video hand opening time, or vHOT)
- Muscle strength (Quantitative Muscle Testing, or QMT total score)
- Mobility (10-Meter Walk/Run Test, or 10mWRT, and Timed Up and Go test, or TUG)
- DM1-Activ, a patient-reported outcome that measures activities of daily living (e.g., taking a shower, visiting family or friends, and walking up stairs)
- Acceptable safety and tolerability with most treatment emergent adverse events (TEAEs) mild or moderate in participants with DM1 and did not result in discontinuation.
- Two severe, serious AEs occurred in two participants in the 2 mg/kg and 4 mg/kg dose cohorts, with one participant discontinuing the study in the 4 mg/kg cohort. One of these SAEs was deemed drug-related.
"We are pleased that The New England Journal of Medicine recognizes the significance of the Phase 1/2 MARINA data. The favorable safety profile, coupled with robust analyses of exploratory endpoints in our del-desiran program reinforce our belief that this investigational therapy may offer a transformational treatment option for people living with DM1 and their families," said Sarah Boyce, President and Chief Executive Officer at Avidity. "We remain focused on advancing the ongoing Phase 3 HARBOR study of del-desiran, which is on track to be the first globally approved drug for DM1."
Del-desiran (4 mg/kg) is currently being assessed in the global Phase 3 HARBOR™ study in people living with DM1 who are age 16 and older and in the ongoing HARBOR open-label extension (HARBOR-OLE™) trial with all the participants who completed the Phase 1/2 MARINA trial. The global Phase 3 HARBOR study completed enrollment in July 2025 and a 54-week topline data readout is expected in the second half of 2026.
About the Phase 3 HARBOR™ Trial
The global Phase 3 HARBOR™ trial is a randomized, placebo-controlled, double blind pivotal study designed to evaluate del-desiran in approximately 150 people (age 16 and older) living with DM1. The trial is being conducted at approximately 40 sites globally. Patients are administered either del-desiran or placebo (1:1) every eight weeks. HARBOR is designed to assess multiple key functional aspects of DM1. The primary endpoint is video hand opening time (vHOT), a measurement of myotonia, which is a hallmark symptom of DM1. Key secondary endpoints include muscle strength as measured by hand grip strength and quantitative muscle testing (QMT) total score, and activities of daily living as measured by DM1-Activ. All study participants, regardless of whether they receive active treatment or placebo, have the option to enroll into the ongoing open-label extension trial. For more information about the HARBOR trial, visit http://www.clinicaltrials.gov and search for NCT06411288. For more information about the HARBOR-OLE trial, visit http://www.clinicaltrials.gov and search for (NCT07008469).
About the Phase 1/2 MARINA® Trial
The MARINA® trial was a randomized, double-blind, placebo-controlled, Phase 1/2 clinical trial that enrolled 38 adults with DM1. The primary objective of this study was to evaluate the safety and tolerability of single and multiple ascending doses of del-desiran (AOC 1001) administered intravenously. The MARINA trial assessed the activity of del-desiran (AOC 1001) across key biomarkers, including reduction of DMPK mRNA in skeletal muscle and amelioration of aberrant alternative splicing. Though the Phase 1/2 trial was not powered to assess functional benefit, it explored the clinical activity of del-desiran (AOC 1001) in multiple measures of muscle function including myotonia, muscle strength, measures of mobility as well as patient reported outcomes and quality of life measures. Patients had the option to enroll in MARINA-OLE™, an open-label extension study, at the end of the post-treatment period. For more information on this study click here or visit http://www.clinicaltrials.gov and search for NCT05027269.
About Myotonic Dystrophy Type 1
Myotonic dystrophy type 1 (DM1) is a rare, hereditary (autosomal dominant), progressive neuromuscular disease that shortens life expectancy and requires life-long care caused by a triplet-repeat in the DMPK gene, resulting in a toxic gain of function mRNA. The disease is highly variable with respect to severity, presentation and age of onset, however, all forms of DM1 are associated with high levels of disease burden. DM1 is characterized by multisystemic manifestations including myotonia and progressive muscle weakening and may be underrecognized because it presents heterogeneously across skeletal, cardiac, and smooth muscles, leading to impairment of the cardiovascular, gastrointestinal, respiratory, ocular, and/or endocrine systems. Currently, there are no approved drugs for people living with DM1.
About del-desiran
Del-desiran, utilizing Avidity's AOC platform technology, is designed to address the underlying genetic cause of DM1 by reducing levels of toxic DMPK mRNA. Del-desiran consists of a proprietary monoclonal antibody that binds to transferrin receptor 1 (TfR1) and is conjugated to a siRNA that targets DMPK mRNA. Del-desiran is currently being assessed in the global Phase 3 HARBOR™ trial and in the ongoing HARBOR-OLE™ trial in people with DM1. Long-term data from the MARINA-OLE trial showed reversal of disease progression in people living with DM1 across multiple endpoints including video hand opening time (vHOT) as a measure of hand function and myotonia, muscle strength and activities of daily living when compared to END-DM1 natural history data. Del-desiran has received Breakthrough Therapy, Orphan Drug and Fast Track designations by the
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 also advancing two wholly-owned precision cardiology development candidates addressing rare genetic cardiomyopathies. In addition, Avidity is broadening the reach of AOCs with its advancing and expanding pipeline including programs in cardiology and immunology through key partnerships. Avidity is headquartered in
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 meaningfulness of the del-desiran data from the MARINA® study; the potential for del-desiran to offer a transformational treatment option for DM1 and become the first globally approved drug to treat DM1; the status of the clinical study of del-desiran; Avidity's plans to present additional data from the HARBOR™ study and the timing thereof; the characterization of data associated with del-desiran from the MARINA study and the impact of such data on the advancement of del-desiran; the design, goals and status of the MARINA, MARINA-OLE™ and HARBOR studies; Avidity's plans and expectations to advance its clinical programs, and the timing thereof; and Avidity's platform, planned operations and programs. 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 beyond its control, including, without limitation: analysis of new data may lead to conclusions different from those established in the MARINA trial of del-desiran, and such data may not meet Avidity's or regulators' expectations; unexpected adverse side effects to, or inadequate efficacy of, del-desiran that may delay or limit its development, regulatory approval and/or commercialization; later developments with the FDA and other global regulators that could be inconsistent with the feedback received to date regarding del-desiran and which could delay its currently anticipated timelines; Avidity's approach to the discovery and development of product candidates based on its AOC™ platform is unproven; potential delays in the HARBOR study; Avidity's dependence on third parties in connection with clinical testing and product manufacturing; legislative, judicial and regulatory developments in
Investor Contact:
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FAQ
What did Avidity (RNA) report about del-desiran DMPK mRNA reduction in Feb 2026?
How did del-desiran affect clinical measures like myotonia and mobility in the MARINA trial?
What safety issues did Avidity (RNA) disclose for del-desiran in the Phase 1/2 MARINA study?
When will Avidity (RNA) report Phase 3 HARBOR topline results for del-desiran?
Does the NEJM publication change development plans for del-desiran at Avidity (RNA)?
What dose levels of del-desiran were tested in the MARINA trial (RNA) and how were participants randomized?
