Almost 100 SARS-CoV-2 vaccines in clinical development
India is struggling with a surge in daily Covid-19 cases, while vaccination is lagging behind. The country of 1.4 billion people has vaccinated <10% of its population with 2.5 million daily doses, down from a peak of 4.5 million earlier in 2021. Local vaccine producers are trying to boost the current monthly output of 70–80 million doses. India has approved domestically manufactured vaccines and Sputnik V, while most Western vaccines are waiting for approval.
More field-use data confirm the effectiveness of vaccination. A case-controlled study by the US Centers for Disease Control and Prevention (CDC) found that the two mRNA vaccines (Pfizer/BioNTech and Moderna) prevent 64% and 94% of hospitalizations after one and two doses, respectively.Citation1
A UK-based analysis of 52,000 hospitalizations since December 2020 revealed that only 1% of subjects had been vaccinated, most of them with just one of two doses.Citation2 The majority of the 113 deaths in the vaccinated population were frail elderly subjects.
Meanwhile, US has resumed the rollout of the Ad26.COV2.S vaccine (J&J) after reviewing it for safety. The CDC found only 15 cases of severe blood clots among 8 million vaccinated people.
Covid-19 vaccine manufacturers are scaling up production to meet global demand. Moderna is expanding a US-based plant that will boost production output by 50%. In addition, the company signed a deal with Sanofi for the production of additional 200 million doses of the mRNA-1273 vaccine. BioNTech announced it can deliver a total of 3 billion doses of its BNT162b2 vaccine in 2021.
Other SARS-CoV-2 vaccines in development include the two-dose VLP vaccine ABNCoV2 (Bavarian Nordic), which offered protection against UK and South African variants in a preclinical trial, and the oral vaccine VXA-CoV2-1 (Vaxart), which induced mucosal immunity in a Phase 1 trial and also showed cross-reactivity against other coronaviruses.
Checkpoint inhibitors approved for lung and bladder cancers
The PD-L1 inhibitor atezolizumab (Tecentriq, Roche) was approved in EU as a first-line treatment of adults with metastatic non-small cell lung cancer with high PD-L1 expression. The decision is based on Phase 3 IMpower110 trial demonstrating that atezolizumab monotherapy improved overall survival to 20 months compared with 13 months following chemotherapy.
Atezolizumab and another checkpoint inhibitor, the anti-PD-1 MAb pembrolizumab (Keytruda, Merck), were also approved by the US Food and Drug Administration (FDA) as first-line treatment of platinum-ineligible advanced or metastatic urothelial carcinoma. This approval is conditional on further clinical trials. Both MAbs have shown survival benefits in ongoing trials.
PD-1 inhibitor approved as second-line therapy of endometrial cancer
The FDA has granted accelerated approval for the immune checkpoint inhibitor dostarlimab (Jemperli, GSK) for recurrent, mismatch repair-deficient endometrial cancer. In a previous clinical trial involving 71 patients with this condition, 40% reported complete or partial response lasting at least six months.
Endometrial cancer is one of the most common gynecologic malignancies. Most cases can be treated with surgery. The standard of care for recurrent tumors is platinum chemotherapy.
EU committee recommends approval of immunotherapy combination for pleural mesothelioma
The European Medicines Agency’s committee for human products recommended the combination of PD-1 and CTLA-4 inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy, both BMS) as first-line treatment of unresectable malignant pleural mesothelioma. The decision follows results of CheckMate-743 trial, which demonstrated survival benefit over standard-of-care chemotherapy.
Malignant pleural mesothelioma is a rare type of lung cancer connected to exposure to asbestos. Median survival of patients with advanced disease is 12–14 months with 10% survival rate after five years.
New malaria vaccine prevents disease in toddlers
The malaria vaccine R21 adjuvanted with Matrix-M (Novavax) demonstrated ~75% efficacy in a double-blind, randomized trial involving 450 toddlers aged 5–17 months in Burkina Faso.Citation3 The vaccine was administered in four doses in a 0-4-8-52-week regimen. There were 39 cases of malaria after one year in the experimental receiving the highest adjuvant dose, compared to 106 cases in the control group, which received the rabies vaccine. Both cohorts numbered almost 150 children.
The only malaria vaccine in use, the RTS,S vaccine (GSK), showed a ~ 55% efficacy. RTS,S is currently deployed in a small pilot program involving ~650,000 children in malaria-endemic countries of West Africa.
New MAb against RSV prevents disease in infants
The respiratory syncytial virus (RSV) fusion glycoprotein inhibitor nirsevimab (Sanofi & AstraZeneca) protected newborns from lower respiratory tract infections due to RSV. The Phase 3 MELODY trial administered nirsevimab or placebo to 1,500 term and preterm infants and monitored RSV infections in their first season. The primory endpoints were met, but no specific results have been announced.
RSV is the leading cause of hospitalization in infants. A MAb targeting the same part of the virus, palivizumab, is in use. A head-to-head comparison of nirsevimab and palivizumab is underway.
IL-2 agonist enters clinical testing in solid tumors
Safety and antitumor activity of IL-2 and IL-15 mimic NL-201 (Neoleukin Therapeutics) will be assessed in 120 patients with advanced, relapsed, or refractory solid tumors enrolled in a Phase 1 trial. Subjects will receive intravenous NL-201 as monotherapy until disease progression.
NL-201 is a IL-2/IL-15 receptor agonist designed to induce CD8+ T cells and NK cells. It has been compu-tationally optimized to surpass the native ligands in its binding activity.
Disclosure statement
No potential conflict of interest was reported by the author(s).
References
- Tenforde MW, Olson SM, Self WH, Talbot HK, Lindsell CJ, Steingrub JS, Shapiro NI, Ginde AA, Douin DJ, Prekker ME, et al. IVY network; HAIVEN Investigators. Effectiveness of Pfizer-BioNTech and moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years — United States, January–March 2021. Morb Mortal Wkly Rep. 2021;70(18):674–79. doi:10.15585/mmwr.mm7018e1.
- Egan C, Knight S, Baillie K, Harrison E, Docherty A, Semple C Hospitalised vaccinated patients during the second wave, update April ‘21. [accessed 2021 May 6]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/982499/S1208_CO-CIN_report_on_impact_of_vaccination_Apr_21.pdf
- Datoo MS, Natama HM, Somé A, Traoré O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F, et al. High efficacy of a low dose candidate malaria vaccine, R21 in 1 adjuvant matrix-M™, with seasonal administration to children in Burkina Faso. SSRN [Prepr]. 2021. doi:10.2139/ssrn.3830681.