COVID-19 Drug Research Roundup

COVID-19 Therapies:

An inhaled interferon beta (IFN-beta) therapy from Synairgen significantly reduced the rate of hospitalization in patients with COVID-19, according to the recent phase 2 clinical trial of SG016. The investigational COVID-19 treatment, dubbed SNG001, is an IFN-beta formulation used for nebulization, which facilitates direct delivery of the therapy into the lungs. The recent SG016 study included 221 patients with COVID-19 who were either hospitalized or receiving care at home. Hospitalized patients who received SNG001 were significantly more likely to recover from severe lower respiratory illness caused by SARS-CoV-2 than those enrolled in the placebo group. Patients who received the investigational nebulized therapy also showed reduced breathlessness and no limitations on activities. A combined analysis using data from the hospital and the home cohorts showed that patients treated with SNG001 had a 3.41 greater likelihood of recovering compared with patients randomized to placebo.

Eiger BioPharmaceuticals’ peginterferon lambda (Lambda) has been added to the phase 3 TOGETHER COVID-19 study, an ongoing, randomized trial assessing multiple treatments in outpatients with newly diagnosed COVID-19. Eiger’s Lambda is a first-in-class, type 3 interferon designed to stimulate immune responses important for inducing protection against viral infections. In the newly added TOGETHER arm that includes a single subcutaneous dose of Lambda, researchers will compare the active intervention and placebo arms in terms of the rates of emergency room visits and/or hospitalizations. The Lambda arm, among the other treatment arms in this study, will aim to enroll up to 800 patients who are considered to be at high risk for complications associated with COVID-19. Currently, the TOGETHER platform study is recruiting patients at 11 sites in Brazil, but investigators may expand to sites in Canada.

The first patient has been enrolled in a phase 2 trial studying Partner Therapeutics’ inhaled Leukine (sargramostim) therapy in nonhospitalized patients with COVID-19 at risk for disease progression. The randomized, double-blind, phase 2 SCOPE trial is investigating whether Leukine, an FDA-approved drug that increases white blood cell production, can lower the risk of disease progression and also reduce the rate of hospitalization in patients with COVID-19. The study plans to enroll up to 400 patients at sites across the U.S. as well as in Latin and South America. Primary endpoints include rates of emergency room visits and hospitalizations. In August 2020, Partner initiated a study to evaluate Leukine’s efficacy in hospitalized patients with COVID-19 who required oxygen. The results from this study have yet to be released.

Eli Lilly has initiated the development of an anti-SARS-CoV-2 antibody that will hopefully combat known COVID-19 variants. This decision falls on the heels of a recent FDA decision to revoke the single-use emergency authorization of the pharma’s COVID-19 antibody therapy bamlanivimab after concerns it wasn’t effective against emerging SARS-CoV-2 strains. Lilly’s bamlanivimab, an antibody born from a collaboration with AbCellera, previously demonstrated a lack of robust efficacy against B.1.351, a highly infectious COVID-19 variant. In response, AbCellera evaluated the blood of a convalescent patient who had recovered from COVID-19 and discovered another antibody candidate, LY-CoV1404, which binds to a component of the receptor-binding domain. AbCellera, Lilly and other research partners examined the efficacy of LY-CoV1404 against the original COVID-19 strain as well as variants B.1.1.7, B.1.351, P.1, B.1.526, B.1.427 and B.1.429. The antibody fully neutralized the tested variants and featured a potency against the original variant between 9 ng/mL to 22.1 ng/mL. Based on these preclinical data, Lilly has entered LY-CoV1404 into the BLAZE-4 trial to see if the antibody retains its neutralization potency in patients with mild-to-moderate COVID-19. The therapy will be given alone or with other monoclonal antibodies.

Biotech company Adagio Therapeutics has treated its first patient in a phase 2/3 COVID-19 trial of ADG20, a monoclonal antibody. The new pivotal trial, referred to as EVADE, was initiated based on positive preliminary data from an ongoing phase 1 trial of healthy volunteers. The EVADE trial is a global study that will be conducted at more than 100 sites. Investigators will examine whether a single, intramuscular injection of the therapy is effective for preventing COVID-19 both before as well as after exposure to the novel coronavirus. The early-phase study showed that a single intramuscular dose of ADG20 was well-tolerated at up to 600 mg per dose. The pharmacokinetic data suggested the therapy could offer up to 12 months of protection against a SARS-CoV-2 infection. Also, the initial serum virus neutralizing activity of ADG20 against COVID-19 was similar to that seen in patients who received an mRNA COVID-19 vaccine.

COVID-19 Vaccines:

Pfizer and BioNTech announced Friday that they have submitted the required six months of clinical data on their jointly developed COVID-19 vaccine to the FDA, beginning the process of rolling review of their biologics license application (BLA). If the BLA is approved, the mRNA vaccine would be the first to win full FDA approval. The vaccine received Emergency Use Authorization (EUA) for use in patients age 16 and older in December. The companies will submit the remainder of the data required for the BLA — manufacturing and facility information — in the coming weeks. Pfizer and BioNTech also have requested expansion of the current EUA to allow the vaccine to be administered in adolescents age 12 to 15. Once the companies have collected six months of safety and efficacy data on this age group, they plan to submit a supplement to the BLA.

Novavax has launched a pediatric expansion of the phase 3 PREVENT-19 trial studying the company’s recombinant protein vaccine, NVX-CoV2373, against COVID-19. The additional treatment arm will include up to 3,000 patients between the ages of 12 and 17 who will be treated with the vaccine across 75 U.S. sites. The objective of this expansion study is to examine the efficacy, safety and immunogenicity of NVX-CoV2373 in these adolescent patients. Two-thirds of participants will be randomized to two doses of the vaccine, while one-third will receive two doses of placebo. Both the vaccine and the placebo doses will be administered 21 days apart. At six months following the initial vaccinations, a blinded crossover will take place to ensure each adolescent receives the active vaccine candidate. Investigators will monitor patients for up to two years after the final dose to examine long-term safety outcomes.

Serum Institute of India’s (SII) COVID-19 vaccine, Covovax, will likely enter late-stage clinical trials by the middle of May. This is based on a recommendation from the Data Safety Monitoring Board, which recently reviewed initial safety data of 200 patients who received the vaccine in a phase 2 clinical trial. The phase 3 trial has also been given the green light from the Drugs Controller General of India. Currently, the SII and the Indian Council of Medical Research are conducting a phase 2/3 randomized study evaluating the safety and immunogenicity of Covovax in adults in India. A total of 19 sites across India are participating in the study. In addition to Covovax, the SII also produced the Covishield vaccine with partners AstraZeneca and Oxford University. Novovax, another SII partner, entered into a license agreement with SII last year to develop and commercialize Novovax’s NVX-CoV2373 vaccine for India as well as for other low- and middle-income countries.

New data from a phase 1 trial suggests Vaxart’s COVID-19 vaccine candidate VXA-CoV2-1 features broad cross coronavirus activity. In the 9-person, open-label study, researchers found that VXA-CoV2-1 generated higher CD8+ T-cell responses than those observed with the currently authorized COVID-19 vaccines from Moderna and Pfizer/BioNTech. According to the findings, the authorized mRNA vaccines induced fewer T-cell responses when pitted against Vaxart’s vaccine candidate. Vaxart also believes the T-cell responses against the S and N proteins of the virus offers hints that VXA-CoV2-1 may be effective against new SARS-CoV-2 variants. The investigators also found that immunoglobulin A antibodies were triggered in the mucosa. This finding suggests the mucosal responses could have cross-reactive activity against various other coronaviruses not related to COVID-19, including SARS-CoV-1, MERS and the common cold viruses 229E, NL63, HKU1 and OC43.

Piedmont Health’s Piedmont Atlanta Hospital, in partnership with Moderna, has become the first to launch a trial to evaluate Moderna’s COVID-19 vaccine in liver and kidney transplant recipients. The COVE Transplant clinical trial began last month and has enrolled eight transplant recipients and two control participants. The target enrollment is set at 220 transplant recipients and 20 healthy volunteers. The findings from this study could hold important clinical implications, given patients who receive transplants are at high risk of severe COVID-19-related outcomes. A recent study has also found that organ transplant patients and other immunocompromised individuals do not generate sufficient antibody levels against SARS-CoV-2 after an injection with a COVID-19 vaccine. Only 17 percent out of 436 participants in that Johns Hopkins study had detectable antibodies following the first COVID-19 injection.

HDT Bio and its Indian partner Gennova Biopharmaceuticals have launched a phase 1/2 trial to evaluate the safety and immunogenicity of a COVID-19 vaccine candidate in healthy participants. The vaccine, developed by the two companies in July 2019, uses a lipid inorganic nanoparticle formulation that delivers immune-stimulating ribonucleic acid fragments to specific targeted cells. HDT Bio and Gennova suggest that even a reduced dose of the vaccine can stimulate the immune system, which could improve safety and ultimately reduce costs associated with production. HDT Bio recently stated that additional clinical trials of the vaccine are planned to start in the U.S. and Brazil sometime this year.

The Institute for Biological Research in Israel is considering hitting the restart button on an ongoing trial studying the BriLife COVID-19 vaccine. This consideration was proposed after findings from a phase 1/2 trial show that a single but high dose of the two-dose vaccine was just as effective as both vaccine doses. Relaunching the study could help researchers know for sure that one dose will be as effective and as safe as two doses in a larger study population. But the move would likely delay getting the vaccine to the public, if it ultimately receives approval. Data from currently running clinical trials of the BriLife vaccine have not yet been publicly disclosed. Likewise, little is known regarding the vaccine’s efficacy and safety as it relates to authorized vaccines from Moderna and Pfizer. Israel’s Institute for Biological Research also recently announced it will move its vaccine clinical trials from Israel to Argentina, since many Israelis have already received a COVID-19 vaccine.

Moderna believes a COVID-19 vaccine booster shot can increase the body’s immune response to several COVID-19 variants, according to new human trial data. Study volunteers were given a third dose of the company’s authorized mRNA-1273 vaccine or mRNA-1273.351, a booster vaccine specifically targeting the B.1.351 variant. In the patients who received the third mRNA-1273 shot or the mRNA-1273.351 booster, there was an increase in neutralizing antibodies after vaccination to levels either similar or higher to those observed against the original COVID-19 strain. At 15 days following the booster shot, the investigators found the variant-specific vaccine was more effective than the currently authorized COVID-19 vaccine at increasing levels of antibodies against the B.1.351 strain. Overall, safety and tolerability of the shots were comparable to the safety and tolerability findings from the previous phase 2 and 3 trials of the original vaccine. Currently, Moderna is testing a combination vaccine termed mRNA-1273.211 in a treatment arm of a phase 2 study.

Health Canada has expanded authorization for Pfizer’s and BioNTech’s COVID-19 vaccine BNT162b2 for use in children between the ages of 12 and 15. Canada decided to expand its authorization based on phase 3 pediatric trial data that showed the vaccine generated robust antibody responses in adolescents. The study included 2,260 patients between 12 and 15 years of age. There were no cases of COVID-19 among participants who received the vaccine, while 18 participants in the placebo arm developed the disease during the study. Side effects were considered consistent with those reported in study participants between the ages of 16 and 25. The FDA is considering a similar pediatric authorization for the vaccine in the U.S., and regulators in the European Union are currently reviewing an expanded use filing for the vaccine.