The Administration for Strategic Preparedness and Response (ASPR) announced yesterday that it will give drugmaker Shionogi, Inc, $375 million to develop a drug to prevent COVID-19 infection in people who are immune compromised.

The drug is a long-acting formulation of S-892216, a protease inhibitor that blocks the main protease of SARS-CoV-2 and prevents the virus from making copies of itself in human cells. Designed for pre-exposure prophylaxis (prevention), it would be given to immune compromised people, who may not mount an adequate immune response to vaccines, before they're exposed to the virus. 

Shionogi is receiving the funding from Project NextGen, a $5 billion program led by ASPR's Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases.

"At BARDA, we will be working with Shionogi to accelerate development of this preventative therapeutic to help protect vulnerable Americans," BARDA Director Gary Disbrow, PhD, said in a press release.

Shionogi plans to file an Investigational New Drug application and begin phase 1 clinical trials this year.

CARB-X funds peptide antibiotic

In other drug-development news, CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) announced yesterday that it is awarding $610,000 to Justus Liebig University Giessen in Germany to develop a first-in-class peptide antibiotic.

The money will help researchers at the university define a lead optimization path for a direct-acting peptide therapeutic that targets the BamA protein in gram-negative bacteria. BamA plays a critical role in building the outer membrane of gram-negative pathogens, which acts as a protective barrier by limiting the effectiveness of traditional antibiotics.

"Since BamA is involved in essential processes for the survival of a wide range of Gram-negative pathogens, an optimized peptide antibiotic targeting this protein could have broad-spectrum activity, with a potential for a lack of cross-resistance to current therapies," Erin Duffy, PhD, chief of research and development at CARB-X, said in a press release.

With the award, CARB-X has now funded 108 early-stage projects designed to prevent, diagnose, and treat antibiotic-resistant bacteria.

A randomized controlled trial in Uganda found that seasonal malaria chemoprevention (SMC) with two different regimens effectively reduced malaria incidence in children under 5, with no safety concerns, researchers reported this week in The Lancet Infectious Diseases.

The three-arm, open-label, cluster-randomized trial, conducted in 2022 in a region of Uganda where malaria transmission is highly seasonal, enrolled and randomly assigned children in 380 villages 1:1 to receive SMC with sulfadoxine-pyrimethamine combined with amodiaquine (SPAQ) or dihydroartemisinin-piperaquine, and an additional 47 villages to a control group that received no SMC. 

The primary end point was confirmed malaria incidence. While a previous trial found that SMC with SPAQ reduced malaria in children by 92%, concerns about parasite resistance to sulfadoxine-pyrimethamine in East and Southern Africa has prompted the need to evaluate alternative regimens.

Among the 3,881 children enrolled (1,755 in the SPAQ group, 1,736 in the dihydroartemisinin-piperaquine group, and 380 in the control group), malaria incidence rates were 0.90, 0.80, and 18.26 cases per 100 person-months, respectively. SPAQ and dihydroartemisinin–piperaquine reduced malaria risk by 94% (hazard ratio [HR], 0.06; 95% confidence interval [CI], 0.04 to 0.08) and 96% (HR, 0.04; 95% CI, 0.03 to 0.06), respectively, compared with the control group. Based on the prespecified non-inferiority margin of 1.4, there was non-inferiority between the protective effectiveness of dihydroartemisinin–piperaquine and that of SPAQ (HR, 0.90; 95% CI, 0.58 to 1.39).

Concerns about resistance remain

Although five mutations that mediate moderate sulfadoxine-pyrimethamine resistance were prevalent, mutations conferring high-level resistance were rare. No serious or fatal events were reported in the SPAQ group or the dihydroartemisinin–piperaquine group.

Trial investigators say that while the results are encouraging, parasite resistance remains a critical concern.

"Continued monitoring of drug resistance and exploration of alternative regimens are necessary to ensure the long-term effectiveness of SMC in areas with resistance to sulfadoxine–pyrimethamine," they wrote.