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Human vaccines & immunotherapeutics: news October 2021

The US Food and Drug Administration (FDA) has approved the SARS-CoV-2 vaccine BNT162b2 (Pfizer & BioNTech) for use in children 5-11 years old. The vaccine will be administered in two doses three weeks apart. The dosage level is one-third that for adults and older children. The decision is based on a trial with >2,000 children showing safety and >90% efficacy. The FDA and the European Medicines Agency have approved a booster dose of another mRNA vaccine, mRNA1273 (Moderna), 6 months following the second dose. The license applies to all adults in EU, and to older adults and those from high-risk groups in US. Booster doses have also become available for Americans who received the single-dose Ad26.COV2.S vaccine (J&J). The FDA has adopted a ‘mix-and-match’ approach, which allows the choice of a booster with any of the three approved vaccines irrespective of which first course of vaccination was completed. This regimen has demonstrated stronger immunogenicity than a homologous booster for Ad26.COV2.S recipients. mRNA-1273 can be co-administered with the high-dose quadrivalent influenza vaccine Fluzone (Sanofi), with safety and immunogenicity results comparable to those for separate administration, according to a study with 300 adults ≥65 years of age. Co-administration might help assure better compliance with vaccinations in combating the two infections, to which the elderly are particularly vulnerable, in the upcoming northern winter season. Both mRNA vaccines have been implicated in rare cases of heart inflammation. Two large retrospective studies from Israel confirmed its low prevalence and estimated that 22-27 cases per million vaccinees are associated with BNT162b2. Most cases were mild, and the most vulnerable population was young males. This serious event is much more common following SARS-CoV-2 infection. In contrast, myocarditis concerns stymie the distribution of the mRNA-1273 vaccine. Denmark, Finland, Norway and Sweden recommended against its use in people aged <30, and the FDA delayed the decision on the vaccine’s approval in older children.


Immunotherapeutics targeting the PD-1 pathway approved for new indications
The anti-PD-L1 MAb atezolizumab (Tecentriq, Roche) was approved by FDA for advanced non-small cell lung cancer with high PD-L1 expression, following surgery and chemotherapy. Phase 3 data previously showed that adjuvant atezolizumab reduced the risk of relapse or death by >30% compared to best supportive care.
The PD-1 inhibitor pembrolizumab (Keytruda, Merck) was approved by FDA as first-line treatment with chemotherapy for patients with recurrent or metastatic cervical cancer with high PD-L1 levels. The decision is based on Phase 3 data showing that the combination reduced the incidence of death by >30%.
Another PD-L1 inhibitor, durvalumab (Imfinzi, AstraZeneca), combined with chemotherapy extended overall survival in biliary tract cancer compared to chemotherapy alone. No specific data were released from the Phase 3 TOPAZ-1 trial, which tested firstline durvalumab in almost 700 subjects with advanced disease.

PCV-15 is safe and protective in children
The 15-valent pneumococcal conjugate vaccine Vaxneuvance (Merck) has demonstrated safety and non-inferior immunogenicity compared to PCV-13 (Prevnar 13, Pfizer) in children.
In two trials involving a total of 1,500 infants and children, Vaxneuvance provided higher immunogenicity for the 13 shared strains, plus coverage for two additional strains of Streptococcus pneumoniae. The vaccine was tested in naïve subjects and those who did not complete the Prevnar 13 regimen.
Vaxneuvance has been recommended for adult immunization by advisory committees in US and EU, and it is awaiting a decision for use in children.

FDA expands dupilumab approval to include children with severe asthma
The IL-4 receptor inhibitor dupilumab (Dupixent, Sanofi & Regeneron) can be used in children aged 6-11 years with moderate-to-severe asthma with high eosinophil counts. FDA's decision is based on results of a double-blind, placebocontrolled Phase 3 trial, in which dupilumab combined with the standard-of-care therapy improved lung function and reduced the rate of severe asthma attacks by 65%.

Chikungunya vaccine enters Phase 3 trial
Safety and immunogenicity of the chikungunya vaccine candidate CHIKV VLP (Emergent BioSolutions) is being tested in a randomized, double-blind, placebo-controlled Phase 3 trial. Neutralizing antibodies will be measured three weeks after vaccination in >3,000 healthy volunteers aged 12-64 years.
CHIKV VLP is a virus-like particle vaccine, which has demonstrated safety and immune persistence for at least two years. There is no licensed vaccine against chikungunya, a mosquito-borne virus causing fever and pain in joints, muscles and the head.

Immunotherapy improves grass allergy symptoms in a field trial
The grass-pollen allergy immunotherapeutic Grass MATA MPL (Allergy Therapeutics) reduced daily symptoms and relief-medication use in the exploratory G309 trial. 120 patients were randomized to receive a course of six subcutaneous injections in 6 or 14 weeks or placebo. Improvements in a standardized assessment score of 29% and 37%, respectively, were reported for the two regimens, as well as reduced activity of allergen-specific antibodies.
Grass MATA MPL, which consists of 13 tyrosine-adsorbed grass pollen antigens modified with glutaraldehyde, is designed to induce a switch from Th2 to Th1 responses.

Melanoma vaccine fast-tracked by FDA
The cancer vaccine UV1 (Ultimovacs) has received FDA's fasttrack designation for treatment of unresectable or metastatic melanoma in combination with checkpoint inhibitors. UV1, which targets telomerase overexpressed in many cancer types, demonstrated safety and preliminary efficacy in early trials.
In a recent follow up to one Phase 1 trial, UV1 combined with pembrolizumab achieved 80% overall survival after two years, compared to 60% observed in another study of pembrolizumab alone.

Malaria vaccine will be deployed across Africa
The World Health Organization (WHO) has recommended the malaria vaccine RTS,S/AS01 (Mosquirix, GSK) for use in all African children. Following a pilot trial with 800,000 children from three countries, a WHO advisory panel has concluded the vaccine is safe and should be rolled out in countries with high malaria transmission, even though efficacy against severe disease has been estimated at only 30%.
The recombinant RTS,S/AS0, which is administered in four doses, is the first vaccine used against a parasitic disease. Malaria accounts for ~260,000 deaths of children under 5 in Africa alone.

Cancer vaccine against KRAS has entered clinical trials
The first patients have received the therapeutic KRAS-targeting vaccine ELI-002 (Elicio Therapeutics) in the Phase 1/2 AMPLIFY-201 trial, which will test safety, efficacy and optimal dose of the vaccine following surgery in subjects with KRAS-driven solid tumors, including colorectal, pancreatic and lung cancers.
KRAS is a signaling protein mutated in many cancer types. ELI-002, which consists of mutated KRAS peptides and the CpG adjuvant, is targeted to lymph nodes to elicit T-cell responses.