COVID-19 Drug Research Roundup

COVID-19 Therapies:

The NIH’s National Institute for Allergy and Infectious Diseases has halted enrollment of severely ill COVID-19 patients in a phase 3 trial of Merck’s Rebif (interferon beta-1a) with Gilead Sciences’ remdesivir due to serious adverse events. An interim review of safety data found more adverse events among patients on high-flow oxygen/noninvasive mechanical ventilation who received Rebif compared to those who did not receive the drug. No concerns existed among patients who had less severe COVID-19, and the trial will continue to enroll patients on low-flow oxygen and those not requiring supplemental oxygen.

The FDA has approved a phase 2 study of FSD Pharma’s investigational COVID-19 signature drug, FSD201. The primary objective of the randomized, multicenter trial will be to determine whether the therapy improves time to symptom relief faster than standard of care alone in 352 hospitalized patients with COVID-19. Dosing of the trial’s first patients is expected some time in October 2020.

The FDA has also greenlighted Stemedica Cell Technologies’ phase 2 trial, which will study the company’s intravenous ischemic-tolerant mesenchymal stem-cell treatment in patients with moderate- to-severe COVID-19. Patients in the trial will be randomized to receive either the stem-cell therapy plus placebo or placebo with standard treatment. In emergency use and expanded use programs, Stemedica’s treatment was shown to reduce oxygen requirements within just one to two days of treatment initiation in 14 critically ill patients with COVID-19.

A phase 2 trial in the U.S., launched by GlaxoSmithKline, is studying investigational rheumatoid arthritis drug otilimab in hospitalized patients with COVID-19 who are receiving oxygen or ventilator support. The monoclonal antibody will be administered via a single one-hour infusion and will be compared with placebo plus standard of care in terms of its ability to reduce the effects of the infection on the lungs. The primary endpoint will be the proportion of patients who are alive and free of lung failure at 28 days.

Regeneron Pharmaceuticals has released early data from its 275-patient phase 1/2/3 COVID-19 trial, which show that antibody therapy REGN-COV2 reduced the proportion of patients with COVID-19 who required additional medical visits compared with placebo. Approximately 7.7 percent and 4.9 percent of patients given the high and low dose of the drug, respectively, required additional visits, while 15.2 percent of patients assigned to placebo required additional medical attention. A phase 2/3 portion of this trial is set to enroll up to 1,300 patients who will be followed for 29 days to examine the association between treatment and viral shedding in the upper respiratory tract. Three other late-stage trials are also investigating REGN-COV2 for COVID-19. Currently, a U.S.-based phase 3 trial is testing the therapy in hospitalized patients with COVID-19, and another study is testing the therapy for infection prevention in people who live with individuals who have been infected.

The University of Oxford is getting ready to launch a phase 2 trial of AbbVie’s anti-inflammatory drug adalimumab in patients with COVID-19 who reside in community care homes. The trial will investigate the drug’s anti-inflammatory and prophylaxis effects against the disease. Recruitment of 750 patients across the UK will begin in late October. The Wellcome initiative’s COVID-19 Therapeutics Accelerator, in addition to the Bill & Melinda Gates Foundation and Mastercard, is sponsoring the trial.

COVID-19 Vaccines:

Two leading COVID-19 vaccine developers, AstraZeneca and Moderna, have hit new speed bumps that could delay their promising COVID-19 vaccine candidates, reducing the possibility of a vaccine being ready ahead of the U.S. presidential election on Nov. 3. The FDA has broadened its already-significant investigation into the halted phase 3 trial of AstraZeneca’s AZD1222 after a participant in the UK experienced a serious adverse event. The agency is reportedly asking for data from previous studies of similar vaccines that the same researchers worked on. Meanwhile, Moderna CEO Stéphane Bancel said this week that he doesn’t expect the company to ask the FDA for an Emergency Use Authorization (EUA) for its vaccine before Nov. 25 at the earliest. He had previously indicated that the vaccine could be ready by early November. Bancel says the company just does not have enough supporting data to file for an EUA yet.

Moderna’s COVID-19 vaccine candidate, mRNA-1273, generated an immune response in older adults between the ages of 56 and 71, according to new phase 1 trial data. The study administered two 25 mcg or 100 mcg doses of mRNA-1273 one month apart in 40 healthy adult volunteers. The vaccine was well-tolerated and produced significant binding and neutralizing antibodies against COVID-19. Immune responses in this older cohort were comparable to those observed in younger-aged groups, the study found. Currently, Moderna’s COVID-19 vaccine candidate is being investigated in 30,000 participants in phase 3 testing in the U.S.

The FDA has placed a partial clinical hold on Inovio Pharmaceutical’s planned phase 2/3 trial of its COVID-19 vaccine candidate INO-4800, requesting more information before the trial can begin. The hold was not because of any adverse events related to Inovio’s ongoing phase 1 trial of the candidate, the company said. Rather, the agency had questions about the late-stage study and about the device that will be used in the trial to deliver the vaccine.

Single doses of Johnson & Johnson’s (J&J) COVID-19 vaccine candidate AD26.COV2.S generated a strong antibody response in patients, according to early trial data. The company released interim results of a phase 1/2a trial that compared one and two doses of the vaccine vs. a placebo in 1,045 participants. One group was made up of volunteers age 18 to 55 and another group was comprised of adults age 65 to 75. Nearly all participants who were given a single dose generated antibodies to the coronavirus after 29 days, J&J said.

CureVac has initiated its phase 2 trial of CVnCoV, its messenger RNA COVID-19 vaccine candidate, in Panama and Peru. Enrollment will focus on 690 patients between the ages of 18 and 60 as well as those who are 61 years and over. Patients will receive two vaccine doses 28 days apart. According to CureVac, initial results are expected in the fourth quarter of 2020. Around the time the initial findings are released, the study plans on also launching a 30,000-participant global phase 2b/3 trial to examine the efficacy of the vaccine against COVID-19. Phase 1 testing was launched in June in Germany, and CureVac is in the final stages of cutting a supply deal with the EU for 225 million vaccine doses.

Kangtai Biologics, which has collaborated with AstraZeneca to develop COVID-19 vaccine candidate AZD1222, is working with the UK-based company to produce up to 200 million doses of the vaccine by the end of next year.

COVAXX has safely dosed its first healthy adult volunteers in its phase 1, open-label, dose-escalation trial of COVID-19 vaccine candidate UB-612. The study, conducted in Taiwan, is evaluating the safety, tolerability and immunogenicity of the vaccine in up to 60 healthy adults between the ages of 20 and 55. Ascending doses of the vaccine will be delivered in two intramuscular injections 28 days apart.

A new trial in India has been launched to investigate AstraZeneca’s and Oxford University’s COVID-19 vaccine candidate, Covishield, in 300 volunteers. The Indian Council of Medical Research and the National Institute for Research in Tuberculosis will run the trial.

Russia has announced completion of phase 3 clinical trials of Vector Institute’s coronavirus vaccine, EpiVacCorona. The country’s prime minister has said preparations are being made to approve the vaccine for Russia by Oct. 15.

Researchers from two Chilean universities are gearing up to begin clinical trials of Sinovac’s and Johnson & Johnson’s COVID-19 vaccines following recent approvals made by Chile’s Institute of Public Health. Chile may also play host to a trial from AstraZeneca, which has also applied to start trials in the country.

Dr. Reddy’s Laboratories has not yet filed a formal application to begin phase 3 trials of Russia’s COVID-19 vaccine, Sputnik V, according to India’s Central Drugs and Standards Control Organization. No plans have been made for any Emergency Use Authorization of the vaccine without relevant local data. Still, the first deputy CEO of the Russian Direct Investment Fund (RDIF) has said clinical trials will start in India soon. Additionally, the CEO has said that the RDIF is speaking with Indian companies for contract manufacturing of the vaccine. Russia is also looking to partners in Brazil, China and Korea for a manufacturing deal.