This section highlights FDA-related milestones and regulatory updates for drugs developed by Denali Therapeutics (DNLI).
Over the past two years, Denali Therapeutics has reported clinical trial outcomes, regulatory submissions, approvals, and other FDA events for drugs and therapies such as
DNL593, AVLAYAH, tividenofusp, DNL310, tividenofusp, DNL343, and DNL126. For definitions of regulatory abbreviations such as NDA, BLA, or PDUFA, see the event status legend.
Select a button below to view the list of FDA events for that drug.
DNL593 (PTV:PGRN) FDA Regulatory Events
DNL593 (PTV:PGRN) is a drug developed by Denali Therapeutics for the following indication: Frontotemporal Dementia-Granulin (FTD-GRN).
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- DNL593 (PTV:PGRN)
- Announced Date:
- April 3, 2026
- Indication:
- Frontotemporal Dementia-Granulin (FTD-GRN)
Announcement
Denali Therapeutics Inc announced that it has received notification from Takeda of its decision to terminate the collaboration agreement between the two companies to co-develop and co-commercialize DNL593 (PTV:PGRN).
AI Summary
Denali Therapeutics announced it has received notice from Takeda that Takeda has decided to terminate the collaboration agreement to co-develop and co-commercialize DNL593 (PTV:PGRN). The change ends the formal partnership between the two companies on this progranulin therapy. Denali said it will take responsibility for the program going forward and manage next steps in development and potential commercialization.
Denali plans to continue clinical development of DNL593, which is designed to deliver progranulin to the brain using its TransportVehicle™ technology to help patients with frontotemporal dementia caused by GRN mutations (FTD-GRN). The company expects results from the ongoing Phase 1/2 study by the end of 2026. Denali also said it will pursue regulatory interactions, interim updates, and possible new collaborations as needed while advancing the program for affected patients.
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AVLAYAH FDA Regulatory Events
AVLAYAH is a drug developed by Denali Therapeutics for the following indication: Treatment of Hunter Syndrome (MPS II).
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- AVLAYAH
- Announced Date:
- March 25, 2026
- Indication:
- Treatment of Hunter Syndrome (MPS II)
Announcement
Denali Therapeutics Inc. announced the U.S. Food and Drug Administration (FDA) has granted accelerated approval for AVLAYAH™ (tividenofusp alfa-eknm), the first FDA-approved biologic specifically designed to cross the blood-brain barrier and reach the whole body, including the brain.
AI Summary
Denali Therapeutics announced the FDA has granted accelerated approval for AVLAYAH (tividenofusp alfa‑eknm), the first FDA‑approved biologic engineered to cross the blood‑brain barrier and reach the whole body, including the brain. AVLAYAH fuses IDS to Denali’s TransportVehicle™, which binds the transferrin receptor (TfR) and ferries the enzyme into peripheral tissues and the CNS via receptor‑mediated transcytosis. It is given weekly and will be available in the U.S. after approval.
AVLAYAH is approved for neurologic symptoms in pediatric patients ≥5 kg with Hunter syndrome before advanced neurologic disease. Approval was based on reduced heparan sulfate in cerebrospinal fluid; studies are ongoing to confirm benefit. AVLAYAH is not recommended with other enzyme‑replacement therapies. Denali Patient Services will provide support and access at 844‑DNLI365.
Serious risks include hypersensitivity/anaphylaxis, infusion reactions, anemia and kidney problems; common side effects include infections, fever, GI symptoms, rash and headache. Side effects may be reported to FDA MedWatch or to Denali at 1‑833‑ONE‑DNLI.
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Tividenofusp alfa FDA Regulatory Events
Tividenofusp alfa is a drug developed by Denali Therapeutics for the following indication: Treatment For Hunter Syndrome.
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- tividenofusp alfa
- Announced Date:
- February 5, 2026
- Indication:
- Treatment For Hunter Syndrome
Announcement
Denali Therapeutics Inc announced data from programs in Hunter syndrome (mucopolysaccharidosis type II, MPS II), Sanfilippo syndrome type A (MPS IIIA) and Pompe disease that highlight the potential of its Enzyme TransportVehicle™ (ETV) to enable the delivery of enzyme replacement therapies (ERT) to the whole body, including the brain.
AI Summary
Denali Therapeutics reported data from programs in Hunter syndrome (MPS II), Sanfilippo syndrome type A (MPS IIIA) and Pompe disease that highlight the potential of its Enzyme TransportVehicle™ (ETV) to deliver enzyme replacement therapies (ERT) to the whole body, including the brain. The company emphasized that ETV is designed to ferry therapeutic enzymes across barriers that normally block access to the central nervous system.
Key program updates include tividenofusp alfa (DNL310, ETV:IDS), where a Phase 1/2 case study of two male siblings with non‑neuronopathic MPS II supports the potential to address the full disease spectrum. DNL126 (ETV:SGSH) for MPS IIIA and DNL952 (ETV:GAA) for Pompe disease were also highlighted, with DNL126 progressing toward a global Phase 3 plan. Together, these data suggest the ETV platform may enable ERTs to reach both systemic and brain tissues.
All programs remain investigational and have not been approved by health authorities.
Read Announcement- Drug:
- tividenofusp alfa
- Announced Date:
- October 13, 2025
- Indication:
- Treatment For Hunter Syndrome
Announcement
Denali Therapeutics Inc announced that the U.S. Food and Drug Administration (FDA) has extended its review timeline of the Biologics License Application (BLA) seeking accelerated approval of tividenofusp alfa for the treatment of mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.
AI Summary
Denali Therapeutics Inc. announced that the U.S. Food and Drug Administration has extended its review of the Biologics License Application for accelerated approval of tividenofusp alfa, a potential treatment for Hunter syndrome (MPS II). The Prescription Drug User Fee Act (PDUFA) target date has shifted from January 5, 2026, to April 5, 2026. This three-month extension follows Denali’s submission of updated clinical pharmacology information in response to an FDA request. The FDA classified the submission as a Major Amendment, which automatically adds three months to the review timeline without requesting additional data.
Denali believes the new information does not alter its clinical pharmacology or benefit-risk conclusions. The company is preparing for a possible approval and commercial launch of tividenofusp alfa. Denali’s CEO highlighted the urgency to deliver this therapy to individuals and families affected by Hunter syndrome and affirmed continued collaboration with regulators, physicians and patient advocates.
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DNL310 FDA Regulatory Timeline and Events
DNL310 is a drug developed by Denali Therapeutics for the following indication: Gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B.
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- DNL310
- Announced Date:
- January 29, 2026
- Indication:
- Gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B.
Announcement
Denali Therapeutics Inc. announced the presentation of clinical and preclinical data from its Enzyme TransportVehicle™ (ETV) programs at the upcoming 22nd Annual WORLDSymposium™ to be held February 2-6, 2026, in San Diego, California.
AI Summary
Denali Therapeutics will present clinical and preclinical data from its Enzyme TransportVehicle (ETV) programs at the 22nd Annual WORLDSymposium, Feb 2–6, 2026, in San Diego. Highlights include continued follow-up Phase 1/2 data for tividenofusp alfa (DNL310) for Hunter syndrome (MPS II), preliminary Phase 1/2 results for DNL126 (ETV:SGSH) for Sanfilippo syndrome type A (MPS IIIA), and the Phase 1 study design plus supporting preclinical data for DNL952 (ETV:GAA) for Pompe disease.
Presentations will appear as platform talks and poster sessions covering clinical outcomes, patient and caregiver quality-of-life findings, a sibling case report, and enhanced muscle and brain correction in a Pompe mouse model. PDFs of the presentations will be posted on Denali’s investor events page after the symposium embargo. Denali will also sponsor a satellite symposium, “Transforming Patient Care in MPS II,” on Feb 5 with expert speakers.
Read Announcement- Drug:
- DNL310
- Announced Date:
- December 30, 2025
- Indication:
- Gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B.
Announcement
Denali Therapeutics Inc announced the publication of results from the open-label Phase 1/2 clinical trial of its investigational, next-generation enzyme replacement therapy (ERT), tividenofusp alfa (DNL310), for the treatment of Hunter syndrome (mucopolysaccharidosis type II, or MPS II) in the January 1, 2026 issue of The New England Journal of Medicine.
AI Summary
Denali Therapeutics reported in The New England Journal of Medicine the Phase 1/2 open-label trial results for tividenofusp alfa (DNL310), a next-generation enzyme replacement therapy designed to cross the blood–brain barrier using Denali’s TransportVehicle. The study enrolled 47 children (ages 0.3–13) including both ERT‑naïve and previously treated patients. Key biomarker results showed mean cerebrospinal fluid heparan sulfate fell 91% by Week 24 and remained reduced through Week 153, with 93% reaching levels seen in unaffected children. Urine heparan sulfate fell 88% at Week 24; 58% reached the unaffected range. Serum neurofilament light, a neuronal injury marker, fell 21% by Week 49 and 76% by Week 153, with 85% reaching normal-range levels.
Clinically, liver volume normalized by 24 weeks, hearing improved, and most participants showed gains in adaptive behavior and cognition. The most common treatment‑related adverse events were infusion‑related reactions, which decreased with continued dosing. Tividenofusp alfa remains investigational.
Read Announcement- Drug:
- DNL310
- Announced Date:
- February 6, 2025
- Indication:
- Gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B.
Announcement
Denali Therapeutics Inc
AI Summary
Denali Therapeutics Inc. recently shared encouraging long-term results from their Phase 1/2 study in 47 patients with Hunter syndrome (MPS II). The study found that treatment with tividenofusp alfa led to significant and long-lasting reductions in key biomarkers, with many patients showing improvements in hearing, cognition, and adaptive behavior. These benefits were maintained over a median follow-up period of two years and even up to four years in some cases. The data supports Denali's plan to seek accelerated approval, with a biologics license application expected in early 2025 and a planned U.S. launch for late 2025 or early 2026. Denali is working hard to provide this promising treatment to families affected by MPS II, and the positive results not only highlight progress in addressing both neurocognitive and physical symptoms but also pave the way for further advancements in their lysosomal storage disease programs.
Read Announcement- Drug:
- DNL310
- Announced Date:
- September 3, 2024
- Indication:
- Gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B.
Announcement
Denali Therapeutics Inc announced the outcome of a recent successful meeting with the Center for Drug Evaluation and Research (CDER) division of the U.S. Food and Drug Administration (FDA) providing a path to filing a biologics license application (BLA) for accelerated approval and subsequent conversion to full approval for tividenofusp alfa (DNL310) for the treatment of MPS II (Hunter syndrome).
AI Summary
Denali Therapeutics announced a positive outcome from a recent meeting with the FDA’s Center for Drug Evaluation and Research (CDER). During this meeting, the FDA provided clear guidance on filing a biologics license application (BLA) for tividenofusp alfa (DNL310) under the accelerated approval pathway for treating MPS II (Hunter syndrome). The discussions focused on using cerebrospinal fluid heparan sulfate (CSF HS) as a surrogate biomarker that is reasonably likely to predict clinical benefit. This supportive feedback paves the way for Denali to submit the BLA in early 2025, aiming for accelerated approval with plans to convert to full approval after additional clinical validation. This positive development marks an important step toward addressing the unmet needs of patients with MPS II and reflects collaborative efforts among the drug developers, clinicians, and the broader patient community.
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Tividenofusp FDA Regulatory Events
Tividenofusp is a drug developed by Denali Therapeutics for the following indication: For the treatment of Hunter syndrome (MPS II).
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- tividenofusp
- Announced Date:
- July 7, 2025
- Target Action Date:
- January 5, 2026
- Indication:
- For the treatment of Hunter syndrome (MPS II)
Announcement
Denali Therapeutics Inc. announced that The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of January 5, 2026.
AI Summary
Denali Therapeutics Inc. recently announced significant progress in its development of tividenofusp alfa for treating Hunter syndrome. The U.S. Food and Drug Administration (FDA) granted Priority Review for the Biologics License Application (BLA) under the Prescription Drug User Fee Act (PDUFA). This review comes with a target action date of January 5, 2026, for the agency’s decision.
The FDA’s Priority Review designation highlights the potential impact of tividenofusp alfa as a new treatment option for a rare genetic disorder that affects both cognitive and physical functions. With this milestone, Denali is preparing for a possible commercial launch in the United States, marking an important step forward in addressing an unmet medical need for patients with Hunter syndrome.
Read Announcement- Drug:
- tividenofusp
- Announced Date:
- July 7, 2025
- Indication:
- For the treatment of Hunter syndrome (MPS II)
Announcement
Denali Therapeutics Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for tividenofusp alfa for the treatment of Hunter syndrome (mucopolysaccharidoses type II, or MPS II), a rare and progressive genetic disorder.
AI Summary
Denali Therapeutics Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for tividenofusp alfa for review. This application is seeking accelerated approval to treat Hunter syndrome (mucopolysaccharidoses type II, or MPS II), a rare and progressive genetic disorder caused by a deficiency in the iduronate 2-sulfatase enzyme. The investigational therapy is designed to deliver the missing enzyme throughout the body and across the blood-brain barrier, addressing both physical symptoms and the neurological aspects of the disease. If approved, tividenofusp alfa could become the first significant advancement in enzyme replacement therapy for Hunter syndrome in nearly two decades, providing a potentially transformative option for patients affected by this challenging condition.
Read Announcement- Drug:
- tividenofusp
- Announced Date:
- April 2, 2025
- Indication:
- For the treatment of Hunter syndrome (MPS II)
Announcement
Denali Therapeutics Inc announced that the company's initiation of a rolling submission of a biologics license application (BLA) for accelerated approval of tividenofusp alfa for the treatment of Hunter syndrome (MPS II) has been received by the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA).
AI Summary
Denali Therapeutics Inc. announced that the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research has received its rolling submission for a biologics license application. This submission is for accelerated approval of tividenofusp alfa, a new treatment aimed at patients with Hunter syndrome (MPS II). The application includes data that uses cerebrospinal fluid heparan sulfate as a surrogate endpoint, which may help speed up the approval process.
The company has been working closely with the FDA and is aligned on the data package needed for both accelerated and full approval. Denali expects to complete its BLA submission by the first half of May 2025 and is preparing for a potential U.S. commercial launch in late 2025 or early 2026. This milestone brings Denali one step closer to providing a new treatment option for the Hunter syndrome community.
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DNL343 FDA Regulatory Events
DNL343 is a drug developed by Denali Therapeutics for the following indication: Amyotrophic lateral sclerosis (ALS).
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- DNL343
- Announced Date:
- March 6, 2025
- Indication:
- Amyotrophic lateral sclerosis (ALS)
Announcement
Denali Therapeutics Inc. provided an update that further analyses from Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating eIF2B agonist DNL343 in the treatment of amyotrophic lateral sclerosis (ALS) did not demonstrate a treatment effect on neurofilament light (NfL), a biomarker of neuronal damage, over the 24-week, double-blind period and in a subset of participants that completed an additional 28 weeks in the open-label active treatment extension.
Read Announcement- Drug:
- DNL343
- Announced Date:
- January 6, 2025
- Indication:
- Amyotrophic lateral sclerosis (ALS)
Announcement
Denali Therapeutics Inc announced topline results from an analysis of Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating eIF2B agonist DNL343 in the treatment of amyotrophic lateral sclerosis (ALS).
AI Summary
Denali Therapeutics Inc. announced topline results from Regimen G of the Phase 2/3 HEALEY ALS Platform Trial, which evaluated the eIF2B agonist DNL343 for the treatment of amyotrophic lateral sclerosis (ALS). The study compared 186 patients treated with DNL343 to 139 patients on placebo. Results showed that DNL343 did not slow disease progression over 24 weeks, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) and survival, and it did not improve muscle strength or respiratory function compared to the placebo group.
Despite the lack of efficacy in these primary and key secondary endpoints, DNL343 was found to be safe and well tolerated. Additional analysis, including tests of neurofilament light and other biomarkers, as well as subgroup findings and long-term data from an extension period, are expected to be released later in 2025.
Read Announcement- Drug:
- DNL343
- Announced Date:
- January 6, 2025
- Indication:
- Amyotrophic lateral sclerosis (ALS)
Announcement
Denali Therapeutics Inc announced topline results from an analysis of Regimen G of the Phase 2/3 HEALEY ALS Platform Trial evaluating eIF2B agonist DNL343 in the treatment of amyotrophic lateral sclerosis (ALS).
AI Summary
Denali Therapeutics Inc. announced topline results from Regimen G of the Phase 2/3 HEALEY ALS Platform Trial, which evaluated the eIF2B agonist DNL343 for treating amyotrophic lateral sclerosis (ALS). The study did not meet its primary endpoint of slowing disease progression, as measured by changes in the ALS Functional Rating Scale-Revised (ALSFRS-R) and overall survival at 24 weeks. Additionally, key secondary endpoints such as measures of muscle strength and respiratory function showed no significant difference compared to placebo.
Despite these outcomes, DNL343 was found to be safe and well tolerated by study participants. Denali plans to share further analysis later in 2025, including data on neurofilament light (NfL) and other biomarkers, along with additional subgroup and extended treatment findings, to better understand the therapeutic potential of DNL343 in addressing ALS.
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DNL126 FDA Regulatory Events
DNL126 is a drug developed by Denali Therapeutics for the following indication: For MPS IIIA (Sanfilippo Syndrome Type A).
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- DNL126
- Announced Date:
- January 13, 2025
- Indication:
- For MPS IIIA (Sanfilippo Syndrome Type A)
Announcement
Denali Therapeutics Inc. announced key anticipated milestones for 2025 across its portfolio. Chief Executive Officer, Ryan Watts, Ph.D., will highlight these priorities during a corporate presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, at 11:15 a.m. PDT.
AI Summary
Denali Therapeutics Inc. has outlined its key milestones for 2025, focusing on advancing its portfolio of therapies. One major highlight includes the submission of a biologics license application (BLA) for tividenofusp alfa for Hunter syndrome on an accelerated approval pathway in early 2025, with preparations for a U.S. commercial launch planned for late 2025 or early 2026. The company is also pushing forward with efforts to align with the FDA for accelerated approval of its second program, DNL126, targeting Sanfilippo syndrome Type A. These programs are central to Denali’s strategy to build a broad franchise of TransportVehicleTM enabled enzyme replacement therapies. Chief Executive Officer Ryan Watts, Ph.D., will discuss these priorities and other anticipated milestones during a corporate presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, at 11:15 a.m. PDT.
Read Announcement- Drug:
- DNL126
- Announced Date:
- June 3, 2024
- Indication:
- For MPS IIIA (Sanfilippo Syndrome Type A)
Announcement
Denali Therapeutics Inc announced that the U.S. Food and Drug Administration (FDA) has selected DNL126 for participation in the Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program.
AI Summary
The FDA has selected Denali Therapeutics Inc.’s investigational therapy DNL126 to participate in the START Pilot Program, a new initiative designed to speed up the development of treatments for rare diseases. DNL126 is an enzyme replacement therapy engineered to cross the blood-brain barrier and is being studied for its potential to treat MPS IIIA, also known as Sanfilippo syndrome type A. This selection is based on the drug’s promise for clinical benefit and Denali’s capacity to advance the therapy toward a marketing application. Being part of the START Pilot Program will give Denali access to more frequent and flexible communications with FDA review staff, which is expected to help overcome development challenges and accelerate the overall process. This step underscores both Denali’s commitment to finding treatments for rare neurodegenerative diseases and the FDA’s support for innovative drug development.Read Announcement
BEACON FDA Regulatory Events
BEACON is a drug developed by Denali Therapeutics for the following indication: For Parkinson's Disease.
This drug is under review by the U.S. Food and Drug Administration (FDA).
Below is a timeline of key regulatory milestones for this therapy.
- Drug:
- BEACON
- Announced Date:
- December 5, 2024
- Indication:
- For Parkinson's Disease
Announcement
Denali Therapeutics Inc announced initiation of dosing in a global Phase 2a clinical study, BEACON, of the investigational drug leucine-rich repeat kinase 2 (LRRK2) inhibitor BIIB122 (DNL151) in participants with LRRK2-associated Parkinson's disease (LRRK2-PD).
AI Summary
Denali Therapeutics has begun dosing in its global Phase 2a clinical study, BEACON, to evaluate the investigational LRRK2 inhibitor BIIB122 (DNL151) in patients with LRRK2-associated Parkinson’s disease. This study will involve approximately 50 participants who have confirmed LRRK2 mutations through genetic testing. The trial is designed with a three‐month double-blind treatment period, followed by an open label extension, to assess the safety, tolerability, and biomarker responses to daily oral dosing of BIIB122.
The study aims to explore whether targeting LRRK2 can slow the progression of Parkinson’s disease by addressing underlying lysosomal dysfunction. Denali holds the Investigational New Drug application for this trial and is leading its design and execution in collaboration with a third-party partner, marking an important step in the continued search for disease-modifying therapies for Parkinson’s patients with genetic risk factors.
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