Biohaven Initiates Expanded Access Program for Sublingual BHV-0223 ZYDIS® Orally Dissolving Tablets for Patients with Amyotrophic Lateral Sclerosis (ALS)

NEW HAVEN, Conn., May 9, 2018 /PRNewswire/ -- Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) today announced that it has established an expanded access program (EAP) with sublingual BHV-0223, an investigational drug candidate, for patients with amyotrophic lateral sclerosis (ALS).  Through this program, physicians may be able to obtain BHV-0223 for their eligible patients with ALS at no cost.  BHV-0223 is a sublingual and lower dose formulation of riluzole which employs the Zydis® orally dissolving tablet technology and does not require swallowing tablets or additional fluids. The active ingredient riluzole is the only approved drug therapy for ALS shown to prolong survival.  Biohaven anticipates submitting a New Drug Application (NDA) for BHV-0223 to the U.S. Food and Drug Administration (FDA) in the third quarter of 2018.  Details regarding this EAP, including eligibility criteria, are available at www.earlyaccesscare.com/biohaven

EAPs are regulated by the FDA for the purpose of providing access to drugs in development, prior to regulatory approval for marketing, to eligible patients with serious or life-threatening diseases or conditions for which there are insufficient pharmacologic alternatives.  More information on EAPs is available at www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm. 

"It is great for the ALS community that Biohaven is taking advantage of the FDA's expanded access program," said Calaneet Balas, president and CEO of The ALS Association. "We believe this is the first instance of a company offering expanded access for widespread use in ALS. Such programs enable people with ALS and their doctors to consider the use of investigational drugs."

BHV-0223 40 mg is a ZYDIS^® sublingual tablet administered twice a day, that provides bioequivalent systemic exposures as Rilutek^® (riluzole) 50 mg tablets but with a 20% lower total daily drug burden. Its use is expected to be particularly amenable for patients with trouble swallowing (dysphagia) as it is administered under the tongue, where it dissolves in seconds and does not require swallowing or administration with liquids.

Dysphagia is one of the most critical and debilitating symptoms associated with ALS.   Approximately one-third of ALS patients present with some degree of dysphagia on diagnosis.   As the disease progresses, a majority of patients with ALS will experience dysphagia, and many will experience severe dysphagia, requiring placement of a percutaneous endoscopic gastrostomy (PEG) tube to allow nutrition, fluids and/or medications to be administered directly into the stomach, bypassing the mouth and esophagus.   Even ALS patients with mild or moderate dysphagia who have not yet lost the ability to swallow have difficulty managing small oral boluses such as tablets through the swallowing process.   Biohaven's sublingual formulation obviates the need for swallowing tablets or additional liquids to wash down the tablets. 

Vlad Coric M.D., CEO of Biohaven said, "Recognizing that many ALS patients with dysphagia may be unable to take conventional riluzole tablets for reasons that include difficulty with swallowing, Biohaven is pleased to be able to offer patients living with ALS access to sublingual BHV-0223 via this expanded access program while we prepare to submit our NDA. For those patients with significant dysphagia, waiting for the approval of sublingual BHV-0223 may mean never getting the opportunity to take this drug and receive the benefits of riluzole, the only drug for ALS known to impact survival.  We are happy to help address this pressing need within the FDA's EAP framework."  

Biohaven worked in conjunction with Catalent U.K. Swindon ZYDIS Limited, a subsidiary of Catalent, Inc. (NYSE: CTLT) ("Catalent") to develop the new BHV-0223 ZYDIS formulation of riluzole. Biohaven has also entered into an exclusive agreement with Catalent for the use of the Zydis ODT formulation technology and the active pharmaceutical ingredient riluzole.

Rob Berman M.D., CMO of Biohaven added, "Sublingual BHV-0223 ZYDIS was specifically designed for ALS patients who have difficulty swallowing tablets and to offer a lower dose version of the currently approved active drug ingredient. We understand the urgency of patients' needs and while the EAP is ongoing, Biohaven will be diligently working toward submitting an NDA in the next quarter."

About BHV-0223

BHV-0223 is a Zydis formulation of riluzole for sublingual administration in patient with ALS. As reported in January, sublingual BHV-0223 (40 mg) achieves bioequivalent exposures relative to Rilutek (50 mg).  This was demonstrated in a study with 138 healthy volunteers who were administered BHV-0223 and Rilutek under fasted conditions. In the pre-specified primary analysis, BHV-0223 achieved area-under-the-curve and peak exposures of approximately 90% and 113%, respectively, compared to those generated by Rilutek. The 90% confidence intervals were within the 80% to 125% range that is used to define bioequivalence.  BHV-0223 is designed to meet the needs of patients with ALS. BHV-0223 is a sublingually administered orally dissolving tablet (ODT) that makes use of the unique Zydis® ODT fast-dissolve technology. It is being developed under an exclusive worldwide agreement with Catalent. While riluzole is FDA-approved for ALS, conventional tablets may be difficult to administer to ALS patients, who often have dysphagia or trouble swallowing. By contrast, when BHV-0223 is placed under the tongue, it dissolves in seconds and does not require swallowing. In addition, riluzole is associated with dose-dependent effects on liver tests (transaminases). BHV-0223 offers bioequivalent exposures compared to Rilutek with a 20% lower dose. That is, sublingual administration of 40 mg BHV-0223 results in similar blood exposures to orally ingested 50 mg tablets of Rilutek. Based on this observation and reduced drug exposure to the liver, BHV-0223 may be expected to have a lessened risk for causing liver test elevations. 

About ALS

ALS is a progressive neurodegenerative motor neuron disease that affects nerve cells in the brain and the spinal cord.  The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons. ALS affects up to 20,000 individuals in the United States and typically presents in patients with painless muscle weakness, trouble swallowing and muscle atrophy that ultimately progresses to paralysis, impaired breathing and death.  Since the FDA's approval of riluzole in 1995, only two agents have been approved by the FDA in ALS drug therapeutics and riluzole is the only agent indicated to enhance survival and/or time to tracheostomy.

About Biohaven

Biohaven is a clinical-stage biopharmaceutical company with a portfolio of innovative, late-stage product candidates targeting neurological diseases, including rare disorders. Biohaven has combined internal development and research with intellectual property licensed from companies and institutions including Bristol-Myers Squibb Company, AstraZeneca AB, Yale University, Catalent, Rutgers, ALS Biopharma LLC and Massachusetts General Hospital. Currently, Biohaven's lead development programs include multiple compounds across its CGRP receptor antagonist and glutamate modulation platforms. The company's common shares are listed on the New York Stock Exchange and traded under the ticker symbol BHVN. More information about Biohaven is available at www.biohavenpharma.com.

About Catalent

More products. Better treatments. Reliably supplied.™

Catalent is the leading global provider of advanced delivery technologies and development solutions for drugs, biologics and consumer health products. With over 80 years serving the industry, Catalent has proven expertise in bringing more customer products to market faster, enhancing product performance and ensuring reliable clinical and commercial product supply. Catalent employs approximately 10,000 people, including over 1,400 scientists, at more than 30 facilities across five continents, and in fiscal 2017 generated more than $2 billion in annual revenue. Catalent is headquartered in Somerset, New Jersey. For more information, visit www.catalent.com. 

Forward-Looking Statements

This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of the Company's management. All statements, other than statements of historical facts, included in this press release, including the Company's plans to submit an NDA for BHV-0223, the timing of the expected NDA submission for BHV-0223, the potential benefits of BHV-0223 to patients with ALS and the expectation that BHV-0223 may present a lessened risk for causing liver test elevations than Rilutek, are forward-looking statements. The use of certain words, including "anticipate," "believe" and "will" and similar expressions, is intended to identify forward-looking statements. The Company may not actually achieve the plans and objectives disclosed in the forward-looking statements, and you should not place undue reliance on the Company's forward-looking statements. Various important factors could cause actual results or events to differ materially from those that may be expressed or implied by our forward-looking statements, including uncertainties relating to the timing for submitting an NDA and the potential regulatory approval of BHV-0223. Additional important factors to be considered in connection with forward-looking statements are described in the "Risk Factors" section of the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 6, 2018 and other filings Biohaven makes with the U.S. Securities and Exchange Commission from time to time. The forward-looking statements are made as of this date and the Company 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.

For further information, contact Dr. Vlad Coric, the Chief Executive Officer at Vlad.Coric@biohavenpharma.com 

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SOURCE Biohaven Pharmaceutical Holding Company Ltd.