NOVEMBER 2017 A Monthly Review of Articles of Interest for the Clinical Community
<This Month's Clinical Focus: CNS - NEUROLOGY>
New Antibodies Target Structures Shared by Proteins Thought to Worsen Several Neurological Diseases
"In an atmosphere where countless
treatments have failed in clinical trials over the last 15 years, the fact
that our approach continues to be effective in rigorous tests should be of
interest to our peers and the industry, even if it runs contrary to
conventional thinking," says corresponding author Fernando Goni, PhD,
research associate professor in the Department of Neurology at NYU School of
The study focuses on proteins that form
important structures in the brain. The instant they form as chains of amino
acids, proteins fold into complex shapes needed to do their jobs.
Unfortunately, proteins can also "misfold" for countless reasons
(genetic abnormalities, toxins, age-associated cell processes, inflammation,
etc.) that eventually cause the diseases addressed by the current study.
Cells and tissues die as misshapen proteins stop working and build up, but
the field has struggled to pinpoint which of these shifting forms to target
as the key drivers of disease.
Many research efforts, including the current
study, seek to design antibodies shaped to attach to and remove the right
targets. Past and ongoing attempts have targeted the initial, short chains of
amino acids that serve as basic, repeating structural units (monomers) of
each misfolded protein. Still others targeted end-stage fibrils, each made of
thousands of monomers, which accumulate in plaques and tangles that tissues
cannot eliminate. Neither approach has yielded an effective therapy.
"This publication details the first system for making antibodies that truly target only toxic oligomers of misfolded proteins dominated by beta sheets across several diseases, and without regard to the amino-acid makeup of each misfolded protein's monomer," says Goni.
Biohaven Completes Enrollment In The First Of Two Pivotal Phase 3 Clinical Trials Of Rimegepant
Rimegepant, a 2nd generation oral CGRP-Receptor Antagonist, is
for the acute treatment of Migraine
Pharmaceutical Holding Company Ltd. announced that it is completing
enrollment in the first of its two registrational Phase 3 clinical trials,
Study BHV3000-301, to establish the safety and efficacy of orally-dosed
rimegepant. Study BHV3000-301 has enrolled over 1,400 subjects since
July 2017. Rimegepant is a second generation, oral, calcitonin gene
related peptide (CGRP) receptor antagonist being developed for the acute
treatment of migraine. Rimegepant has composition of matter protection until
2030, not including patent term adjustment or any potential patent term
extension. Rimegepant is one of only two small molecule CGRP-receptor
antagonists in late stage clinical development.
CGRP-receptor antagonists represent a novel
class of drug candidates designed to block the molecules in the body
responsible for pain and associated symptoms that occur during a migraine
attack. Additionally, large numbers of migraine patients, especially those
with cardiovascular disease or hypertension for whom existing treatment
options such as triptans are contraindicated, may benefit from safe and
effective oral CGRP-receptor antagonists since this class of drugs is not
associated with vasoconstriction.
Vlad Coric, M.D., Chief Executive Officer at Biohaven commented, "Completing enrollment in this large Phase 3 pivotal trial in four months reflects the high unmet need of people with migraine and dissatisfaction with current treatment approaches. Our team has focused on advancing small molecule CGRP-receptor antagonists in convenient and easy to use oral or intranasal formulations for patients to control migraines when and where a debilitating attack hits. We want to give patients the means to control their migraines in their own hands—tablets comprise the vast majority of migraine therapy prescriptions reflecting patient preference while nasal formulations provide rapid, non-invasive treatment. Based upon our Phase 2 data, we believe our lead candidate, rimegepant, has the potential to be a best-in-class and first-in-class treatment option for the acute treatment of migraine."
In a previously completed Phase 2b clinical trial, the 75 mg dose of rimegepant was observed to have achieved a statistically significant improvement compared to placebo at two hours post-dosing on all four key migraine symptoms: pain, nausea, photophobia and phonophobia. To the Company's knowledge, rimegepant is the only oral, small molecule CGRP-receptor antagonist currently in development that has achieved statistically significant improvements on all four of these key migraine symptoms within a single study. Rimegepant treated patients also experienced durable efficacy, achieving statistically higher rates of pain freedom at 24 and 48 hours post-dosing compared to placebo. Durability of treatment response is an important unmet need not fulfilled by current treatment options.
Image credits: Antibody Defense courtesy of Pixabay by WerbeFabrik CC0 License; Migraine courtesy of Pixabay by TypographyImages CC0 License
GET TO KNOW US!
RESEARCH - TRIAL RESCUE SERVICES - PROJECT & DATA MANAGEMENT -
About Criterium Inc. Criterium Inc. www.criteriuminc.com is a global, full-service, technology-driven contract research organization that offers a unique mix of high-quality, innovative clinical research solutions for the biopharmaceutical, pharmaceutical, medical device, and CRO industries.