Biohaven has established an expanded access program (EAP) with sublingual BHV-0223, an investigational drug candidate, for patients with amyotrophic lateral sclerosis (ALS). 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.
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.
"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."
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox! Sign up now!
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.
Biohaven worked in conjunction with Catalent U.K. Swindon ZYDIS Limited, a subsidiary of 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.
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.