H. Lundbeck A/S’ antibody-based migraine therapy, Vyepti (eptinezumab-jjmr), received FDA approval as the first and only intravenous preventive treatment for adults. It enters a market forecast to grow to $7 billion by 2027. Vyepti is the fourth antibody targeting calcitonin gene-related peptide (CGRP) to reach the market and comes with an unconventional dosing schedule: infused 30 minutes every three months while the other currently approved antibodies are subcutaneously administered.

Another CGRP drug, Biohaven Pharmaceutical Holding Co. Ltd.’s Nurtec ODT (rimegepant), received FDA approval for treating migraine in adults. The company’s sales force is marshalling itself for a March launch, and a Cortellis analysis anticipates sales could soar to $1.03 billion in 2024, though Nurtec will have to compete with drugs such as Ubrelvy (ubrogepant, Allergan plc), which received FDA approval in December for acute migraine treatment, and Reyvow (lasmiditan, Eli Lilly and Co.), a 5-HT 1f agonist approved by the FDA in October, also for acute migraine. Nurtec is the first CGRP receptor antagonist on the market as an orally disintegrating tablet. It is also New Haven, Conn.-based Biohaven’s first FDA-approved product and the second oral small-molecule CGRP antagonist to be approved after Ubrelvy.

It was third time lucky for Acacia Pharma Group plc, as the FDA finally gave approval to Barhemsys (amisulpride) as a rescue treatment for surgical patients suffering postoperative nausea and vomiting (PONV), despite standard-of-care treatment. The product becomes the first antiemetic to be approved for second-line treatment, opening up a U.S. market of an estimated 16 million patients per annum who experience PONV even though they have received standard prophylaxis.

On the other side of the coin, the FDA’s Oncologic Drugs Advisory Committee voted 13-2 against recommending approval of Steba Biotech SA’s NDA for Tookad (padeliporfin dipotassium) for injection in men with localized early stage prostate cancer.

BioWorld Neurological Diseases index on a roll

Investors are keeping a close eye on the progress of companies involved in developing medicines targeting the central nervous system and, in the main, their reaction has been generally positive. The BioWorld Neurological Diseases index, a price-weighted index of public biopharmaceutical companies that are focused on developing therapies to treat neurological diseases, closed the year up more than 16% and after, a dip in January, is now tracking up more than 12% by market close on Friday, Feb. 21, well ahead of the general markets for the same period.

Coronavirus tanks financial markets

Although the World Health Organization (WHO) acknowledged COVID-19 is spreading, it has not yet reached pandemic disease status. The statement did little to comfort the nerves of investors Feb. 24 as they exited global markets big time in the wake of an eruption of new infections in Italy, Iran and South Korea. All major European stock indices dropped about 3%, as did the Dow Jones Industrial Average, which shed 3.5% of its value. Biopharmaceutical equities were also pulled down, with the BioWorld Biopharmaceutical index falling about 2%. The fall was attenuated by index members who have announced they are working on virus treatments.

In other news related to COVID-19: Cocrystal Pharma Inc. entered a license agreement with Kansas State University Research Foundation to further develop certain broad-spectrum antiviral compounds for the treatment of norovirus and coronavirus infections. Sichuan Clover Biopharmaceuticals Inc. entered a research collaboration with Glaxosmithkline plc for its protein-based coronavirus vaccine candidate (COVID-19 S-Trimer). GSK will provide Clover with its pandemic adjuvant system for further evaluation of S-Trimer in preclinical studies.

Vir Biotechnology Inc. and Wuxi Biologics Co. Ltd. will collaborate to advance and produce human monoclonal antibodies to treat the COVID-19. The companies will work together on the clinical development, manufacturing and commercialization of Vir’s antibodies. Wuxi will conduct cell line development, process and formulation development, and initial manufacturing for clinical development. If the antibodies receive regulatory approvals, Wuxi has the rights to commercialize therapies in greater China, and Vir has the rights to commercialize therapies in all other markets worldwide.

Apeiron Biologics AG disclosed that an investigator-initiated pilot study of APN-01 is getting underway in Guangzhou, China. The drug, a recombinant form of human angiotensin-converting enzyme 2 (ACE2), was the subject of a 2010 license agreement potentially worth up to $329 million with Glaxosmithkline plc, which conducted two phase II trials, in acute lung injury or acute respiratory distress syndrome and in pulmonary arterial hypertension, as well as a phase I study in healthy volunteers to assess its effects on hypoxia after exercise. However, it dropped the drug in 2019 as part of a widespread cull of its respiratory disease pipeline.

Ascletis Pharma Inc. advanced its coronavirus pneumonia clinical trial of oral Ganovo (danoprevir) and ritonavir combination therapy, as the company noted that three patients were discharged from a hospital after treatment.

Tonix Pharmaceuticals Inc. entered a collaboration with Southern Research to support the development of a vaccine, TNX-1800 (live modified horsepox virus vaccine for percutaneous administration), to protect against COVID-19, based on Tonix’s horsepox vaccine platform.

Deals of the week

Bicycle Therapeutics plc said Roche Holding AG's Genentech Inc. has agreed to pay $30 million up front for rights to develop and commercialize up to four potential immuno-oncology therapies using the company's bicyclic peptide platform. Bicycle will be responsible for all discovery and lead optimization, while Genentech will take up R&D beyond that. Potential milestone payments, including those tied to regulatory and commercial wins, could push the deal's total value to $1.7 billion, plus royalties.

Biogen Inc. has moved to license multiple Sangamo Therapeutics Inc. programs for $350 million up front plus up to $2.37 billion in development, regulatory and commercial milestone payments. The deal is initially focused on development of ST-501 for tauopathies, including Alzheimer’s disease (AD), ST-502 for synucleinopathies, including Parkinson’s disease, and an undisclosed neuromuscular target. It also includes exclusive rights for nine additional undisclosed neurological targets that Biogen can elect over five years.

1st Biotherapeutics Inc., and Twoxar Pharmaceuticals Inc. said they plan to advance three drug leads aimed at the treatment of glioblastoma into in vivo efficacy testing less than one year from launching their drug discovery collaboration. Boehringer Ingelheim GmbH and Trutino Biosciences Inc. have entered a research collaboration and worldwide licensing agreement based on Trutino’s On-Demand-Cytokine platform. Takeda Pharmaceutical Co. Ltd. has acquired Pvp Biologics Inc. following the conclusion of a phase I proof-of-mechanism study testing TAK-062 (Kuma-062), a super glutenase compound, for the treatment of uncontrolled celiac disease. The two firms entered a development and option agreement in early 2017, under which Pvp was responsible for conducting research and development through phase I in exchange for funding by Takeda related to a predefined development plan. Tetra Bio-Pharma Inc. signed a co-development agreement with Makscientific LLC providing Tetra with access to new molecules targeting the cannabinoid receptors CB1 and CB2. Makscientific will develop the new molecules and Tetra will screen them for efficacy in various indications, including cancer, pain and inflammation.

Financial transactions

Public offerings: Axovant Gene Therapies Ltd. said it closed an underwritten public offering raising gross proceeds of approximately $74.7 million. Oramed Pharmaceuticals Inc. priced an underwritten public offering for gross proceeds of $21 million

Curis Inc. entered a common stock purchase agreement for up to $30 million with Aspire Capital Fund LLC. Redhill Biopharma Ltd. inked a $115 million royalty-backed term loan agreement with Healthcare Royalty Partners

Venture funding: MPM Capital and Dana-Farber Cancer Institute entered an impact investing collaboration, which has raised two funds: the MPM Oncology Innovations Fund with $100 million in capital for creating and investing in early stage biotech companies developing oncology therapeutic technologies; and the Dana-Farber Innovations Research Fund with more than $26 million in pledged donations to support early stage oncology research at Dana-Farber.

Regulatory news

While the staff at the U.S. Department of Health and Human Services (HHS) is currently all hands-on-deck in responding to the COVID-19 outbreak, some of the agencies in the department may have to divert resources to get sponsors of drug and device clinical trials to fill in nearly a decade-long data gap on Clinicaltrials.gov. That’s if a judge’s decision handed down last week stands. Under that order out of the U.S. District Court for the Southern District of New York, HHS must collect and post almost 10 years’ worth of trial results that should be public in accordance with the 2007 FDA Amendments Act (FDAAA), making data from potentially hundreds of clinical trials available for the first time. Those trials would have been completed between Sept. 27, 2007, and Jan. 18, 2017.

The Institute for Clinical and Economic Review (ICER) issued a final evidence report assessing the comparative clinical effectiveness and economic value of three acute treatments for migraine – lasmiditan (Reyvow, Eli Lilly and Co.), rimegepant (Biohaven Pharmaceutical Holding Co. Ltd.) and ubrogepant (Ubrelvy, Allergan plc) – following a review at the January 2020 public meeting of the Midwest Comparative Effectiveness Public Advisory Council (CEPAC), one of ICER’s three independent evidence appraisal committees. Although Midwest CEPAC panelists deemed the evidence adequate to show a net health benefit with the three therapies compared with no treatment, they found the evidence insufficient to show superior net benefit for any of the treatments compared to triptans. All panelists found the evidence insufficient to distinguish the net benefit between rimegepant and ubrogepant, and a majority found the evidence insufficient to distinguish between either of those two or lasmiditan.

Word on the Street: BioWorld's favorite quotes of the week

“The FDA is keenly aware that the outbreak will likely affect the medical product supply chain, including potential disruption to supplier shortages of critical medical products in the U.S.”
FDA Commissioner Stephen Hahn, commenting during a Department of Health and Human Services briefing on the COVID-19 outbreak

“AI can be used to expedite high-accuracy computational chemistry calculations to create accurate 3D structure models of the virus, and simulate molecular-level interactions between the virus and human receptors to understand the mechanism of how the SARS-Cov-2 virus infects the human body. In a few days, we created homology models of the new coronavirus and its protein subunits, and quickly screened through 2,900 FDA approved drugs and over 10,000 Chinese medicine molecules for 3CLPro and PLpro inhibitors, both of which are likely targets for treating the new coronavirus.”
Peiyu Zhang, chief scientist at computation-driven Shenzhen Xtalpi Technology Co. Ltd. Scientists at the company are working to accelerate drug repurposing using new technologies to produce accurate models quickly and share the findings and data with the research community

“Even taking out the time factor we’ve treated, which is shorter than other agents, we’re showing an effect that is at the top of the industry.” [The data make] a good argument that we may be able to run a shorter pivotal trial.”
David Woodhouse, CEO, NGM Biopharmaceuticals Inc., which reported positive preliminary top-line results from the 24-week double-blind, randomized, placebo-controlled fourth cohort of an adaptive phase II study testing aldafermin in nonalcoholic steatohepatitis