New clinical milestones reached as multiple COVID-19 vaccines and therapies advance

08 April 2021

Michael Fitzhugh / BioWorld

Plans for a late-stage test of Valneva SE's COVID-19 vaccine candidate, clinical progress on a different vaccine from Novavax Inc. and advancement for two midstage therapies targeting the virus made clear April 6 that industry efforts to battle the pandemic remain in high gear. Meanwhile, a new journal article on the Abcellera Biologics Inc. and Eli Lilly and Co. asset bamlanivimab pointed to "the feasibility of strategies to rapidly identify neutralizing human mAbs as part of an initial response to an evolving pandemic," researchers wrote in Science Translational Medicine.

How soon, or even if any of the investigational vaccines and therapies – excepting bamlanivimab – might reach global markets is unknown. But the need for both remained clear Tuesday as the World Health Organization reported that new COVID-19 cases rose globally for a sixth consecutive week, with more than 4 million new cases reported in the last week alone. The number of new deaths also increased by 11% compared to last week, with over 71,000 new deaths reported, the organization said.

Valneva's shares (Paris:VLA) saw the biggest reaction to the day's developments, at least initially. Stock in the Saint-Herblain, France-based company jumped as much as 8.5% as it reported more than 90% of people receiving its inactivated, adjuvanted COVID-19 vaccine candidate, VLA-2001, developed "significant levels of antibodies to the SARS-CoV-2 virus spike protein across all dose groups tested." Based on those data, the company plans to start a phase III trial by the end of April 2021, subject to regulatory approval, it said.

"The world needs multiple vaccines as well as booster options," said Valneva CEO Thomas Lingelbach. "Given the potential advantages often associated with inactivated whole virus vaccines, we believe that VLA-2001 has an important role to play."

Though the initial shine wore off Valneva's shares, which lost all their day's gains by the end of trading in Paris, shares in Emeryville, Calif.-based Dynavax Technologies Corp. (NASADQ:DVAX) saw a modest benefit, rising 2.9% to close at $10.13 on April 6. Dynavax is scheduled to supply its CpG 1018 vaccine adjuvant to produce up to 100 million doses of Valneva’s vaccine this year, which could generate revenue of up to $230 million, the company said.

Novavax, too, announced progress on a COVID-19 vaccine candidate, NVX-CoV2373. Under updated trial protocols, all participants in the company's U.K. and U.S. phase III trials will be offered an additional two-dose regimen of either vaccine, for those who originally received placebo, or placebo for those who originally received vaccine. Participants in the company's South Africa phase IIb study will receive either active vaccine for those who initially received placebo, or a booster dose of active vaccine for those who initially received active vaccine, the company said.

"The crossover arms ensure that all participants have access to an active vaccine candidate while allowing Novavax to continue to monitor the safety and efficacy of our vaccine over the long term," said Novavax Chief Medical Officer Filip Dubovsky.

Therapeutics advance, too

Progress on the therapeutics development front remained active, too, this week, with news from Molecular Partners AG that the first patient has been dosed in a phase IIa trial of ensovibep, a molecule designed to bind to the SARS-CoV-2 spike protein at three different locations to prevent the virus from entering cells. The single-arm study, which will enroll up to 40 patients with symptomatic COVID-19, is designed to evaluate dynamics of viral clearance, pharmacokinetics and tolerability of two different doses of ensovibep.

The Zurich-Schlieren, Switzerland-based company said it's also working with its partner on the program, Novartis AG, to start additional trials of ensovibep throughout the first half of this year with the goal of achieving clinical proof of concept and potential submission for an application for emergency use authorization before year-end. That work will include participation in the U.S. NIH’s ACTIV-3 trial as well as a global phase II/III study, Empathy, which will seek to enroll more than 2,100 ambulatory patients to evaluate the ability of ensovibep to prevent disease worsening, hospitalizations and death, Molecular Partners said.

Spotlighting the often long-lasting effects that those suffering with COVID-19 can experience, Azurrx Biopharma Inc. is also getting underway with a trial for COVID-19 patients that targets the potential treatment of COVID-19 related gastrointestinal (GI) infections.

"For many, the after-effects of COVID-19 can be as bad as the disease itself, and this includes a growing number who experience severe GI complications due to what many believe is the ability of SARS-CoV-2 to hide in reservoirs within the GI tract," said Azurrx CEO and president James Sapirstein said.

The phase II study, called Reservoir, is a two-part, two-arm, placebo-controlled trial examining the safety and efficacy of FW-1022, an immediate-release capsule formulation of micronized oral niclosamide the company is developing in partnership with First Wave Bio Inc. The primary efficacy measure of the trial is the rate of fecal SARS2 virus clearance assessed by RT-PCR, comparing the niclosamide arm to the placebo arm.

With an IND for the trial already approved, the Delray Beach, Fla.-based company said Tuesday that it expects to begin enrolling patients this month, with top-line data slated to arrive in the first quarter of 2022. Shares of Azurrx (NASDAQ:AZRX) rose 1.9% on Tuesday, closing just shy of $1. At least four additional trials of niclosamide in COVID-19 are underway, including programs at Ana Therapeutics, Imuneks Farma Ilaç Sanayi Ve Ticaret AS, Union Therapeutics and Daewoong Pharmaceutical Co. Ltd.

Protection from a neutralizing antibody

This week also delivered additional validation for bamlanivimab (LY-CoV555), the world’s first monoclonal antibody specifically developed against SARS-CoV-2 to receive an emergency use authorization from the FDA. Developed by Abcellera and Lilly, the recombinant monoclonal antibody is directed against the spike protein of SARS-CoV-2 and designed, like ensovibep, to block viral attachment and entry into human cells. So far, bamlanivimab has been authorized for use in high-risk COVID-19 patients in the U.S. and more than 15 other countries, as well as in combination with etesevimab in the U.S. and EU.

Researchers reported Monday in Science Translational Medicine that, at least in cynomolgus monkeys, the "biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin converting enzyme 2 binding inhibition, and potent neutralizing activity." Furthermore, they wrote, "antibody treatment may reduce virus replication in the upper airway, thus decreasing viral shedding and transmission following treatment."

Abcellera's chief technology officer, Ester Falconer, said the data, generated prior to the initiation of clinical trials of bamlanivimab in June 2020, "give insights into why bamlanivimab is so potent and further support all of our clinical experience and data showing that bamlanivimab is a safe and effective therapy to treat and prevent COVID-19, when administered early in the course of infection."




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