FDA Issues Complete Response Letter for Biohaven's VYGLXIA (troriluzole) New Drug Application for Spinocerebellar Ataxia

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven said, "We are extremely disappointed on behalf of patients by this action from the Office of Neuroscience at FDA. Beyond substantial evidence of safety and efficacy, patients with rare diseases also deserve an efficient, fair and flexible regulatory process that aligns with the urgency of their high unmet medical needs. Such an approach has been mandated by Congress to empower the FDA with maximum regulatory flexibility for rare disease. As a company, we are committed to advancing innovative treatments and remain dedicated to SCA patients despite all the challenges associated with pursuing therapies for rare diseases. Real-world evidence is an important research approach to assessing and delivering new therapies for complex rare diseases but, despite FDA policy initiatives supporting such tools, the front-line review divisions are not yet embracing FDA policy for the use of real-world evidence or the application of regulatory flexibility for rare disease."

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Unit at Massachusetts General Hospital (MGH), added, "Patients with SCA and clinicians who treat them deserve to be heard on this important NDA filing. There is too much at stake for patients. The FDA decision not to listen to disease experts and respect the patient perspective before taking action represents a misstep in the due process, and a failure to deploy regulatory flexibility to evaluate benefit:risk of a medication that has proven to be safe and effective for this rare, debilitating neurodegenerative disease that has no current treatment."

Dr. Coric added, "The development of VYGLXIA® (troriluzole) by Biohaven embodies a strong scientific process and deep commitment that is critical to bringing safe and effective treatments to patients with rare diseases like SCA. Our efforts over eight years, included developing the f-SARA scale in collaboration with the FDA and a real-world evidence study in SCA that showed VYGLXIA achieved highly consistent, sustained, robust and clinically meaningful treatment effects with a safe, once-daily oral pill that slowed disease progression by 50-70%. The NDA also included data showing VYGLXIA reduced the risk of falls and delayed time to becoming wheelchair bound. The leading SCA experts in the United States directly communicated their support of the troriluzole data to the FDA but unfortunately the Office of Neuroscience's inability to collaboratively engage with Biohaven, the patient community and leading experts leave us with concerns about the lack of regulatory flexibility that is being applied for rare, life-threatening conditions. There are a number of common sense solutions and regulatory tools that the Office of Neuroscience could have applied including a fair hearing of the drug's efficacy and safety risks at an Advisory Committee of experts and patients, post-marketing studies, labelling limitations or an accelerated approval pathway. Patients are waiting and the certainty of disease progression for SCA patients far outweighs any residual uncertainty regarding potential design bias or interpretation of study data, especially when the primary outcome measure was achieved in a study protocol and statistical analysis plan that was reviewed by the FDA prior to data analysis. SCA patients deserved approval of VYGLXIA and certainly a more balanced interpretation of benefit:risks."

Biohaven remains committed to working with the FDA to find a path forward for its NDA for VYGLXIA and plans to meet with the FDA to discuss potential next steps.  

Prioritizing Clinical-Stage, Innovative Assets

Biohaven will prioritize resources to focus all its R&D resources on other key programs from its diversified portfolio. Consistent with Biohaven's enduring commitment as a patient-first drug developer, the company's pipeline is focused on a range of disease indications which have limited or no treatment options and are long overdue for therapeutic innovation.

Bruce Car Ph.D., Chief Scientific Officer at Biohaven, commented, "As drug developers we expect setbacks and our diversified portfolio affords us the opportunity to pivot to other key programs. We remain as resilient as ever in following science in order to make a difference in the lives of people with debilitating diseases. Much important work remains, and we are energized and focused on achieving the critical milestones that lie ahead, mindful that days matter and patients are waiting."

Biohaven is initiating strategic portfolio and cost optimization across multiple programs and will focus forward-looking spend on restructuring of business priorities to achieve an approximately 60% reduction in annual direct R&D spend (which excludes personnel and SBC). This may include pausing or delaying non-priority programs to maintain its cash runway to focus on the priority clinical-stage programs over the next year.

Key areas of focus over the next year will include:

1) Clinical-stage, lead extracellular degraders for IgA nephropathy (BHV-1400) and Graves' disease (BHV-1300);
2) Opakalim, Kv7 ion channel activator, pivotal trials in adult focal epilepsy and depression; and
3) Taldefgrobep alfa, myostatin-activin pathway inhibitor, for SMA and obesity.

About Spinocerebellar Ataxia (SCA) 
Spinocerebellar ataxia is a group of dominantly inherited neurodegenerative disorders characterized by progressive loss of voluntary motor control and atrophy of the cerebellum and brainstem. SCA affects approximately 15,000 people in the United States and 24,000 in Europe and the United Kingdom. Patients experience significant morbidity, including impaired gait leading to falls, loss of ambulation and progression to a wheelchair, inability to communicate due to speech impairment, difficulty swallowing, and premature death. While signs and symptoms can appear anytime from childhood to late adulthood, SCA typically presents in early adulthood and progresses over a number of years. Currently, there are no FDA-approved treatments and no cure for SCA. 

About Troriluzole 
Troriluzole is a new chemical entity (NCE) and third-generation novel prodrug that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of troriluzole is reducing synaptic levels of glutamate. Troriluzole increases glutamate uptake from the synapse, by augmenting the expression and function of excitatory amino acid transporters located on glial cells that play a key role in clearing glutamate from the synapse. The glutamate modulating activity of troriluzole addresses the widely documented glutamate deregulation that underlies neurodegeneration and Purkinje cell dysfunction in patients with SCA. Troriluzole also has the potential to be developed in a number of other diseases associated with excessive glutamate. More information about troriluzole can be found at the Biohaven's website: https://www.biohaven.com/pipeline/glutamate/

About Biohaven 
Biohaven is a biopharmaceutical company focused on the discovery, development and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience and oncology. Biohaven is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's key clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; MoDE™ and TRAP™ extracellular protein degradation for immunological diseases; and myostatin-activin pathway targeting agent for neuromuscular and metabolic diseases, including SMA and obesity. For more information, visit www.biohaven.com.  

Forward-looking Statements
This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the expected timing and amounts of funding under the NPA. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate", "potential first-in-class" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates and regarding reduction in annual direct R&D spend, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates and the expected timing thereof; the potential for Biohaven's product candidates to be successful therapies; the effectiveness of restructuring of business priorities; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

VYGLXIA is a registered trademark, and MoDE and TRAP are trademarks, of Biohaven Therapeutics Ltd.

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Media Contact:
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SOURCE Biohaven Ltd.