Influenza Vaccine, mRNA(Moderna)

GSK has linked its mRNA seasonal flu vaccine candidate to higher immune responses than conventional jabs in a phase 2 trial, emboldening the company to start a pivotal study this month. The limited, variable effectiveness of flu vaccines, which has ranged from 20% to 60% over the past 15 years, presents an opportunity for new shots to disrupt the multibillion-dollar market. GSK’s pursuit of the opportunity centers on mRNA vaccines targeting hemagglutinin (HA) and neuraminidase (NA). While licensed flu shots primarily target HA, there is evidence engaging NA can boost protection. GSK put that idea to the test in a trial that enrolled 971 adults. Participants received different dose levels of one of two mRNA vaccine candidates—which differed in their optimization of B-strain HA—or licensed age-appropriate comparators. The mRNA vaccines caused higher immune responses than standard and high-dose flu shots in younger and older adults, respectively, the company said, adding that the reactogenicity and safety profiles were acceptable. GSK’s press release lacks the numbers behind the conclusions. A researcher shared details of the phase 2 study at the Options XIII Conference for the Control of Influenza on Monday. Based on the data, GSK plans to start a phase 3 trial of the mRNA vaccine candidate with the optimized B-strain HA, FLUm3HA.b-3NA, this month. Phase 3 success could re-energize GSK’s flu vaccine business, which shrank (PDF) by about 25% last year amid “competitive pressure” in the U.S. The opportunity to launch the first mRNA flu vaccine has already passed, but there is room to improve on the first-generation product. Last month, Moderna won FDA approval for an mRNA-based flu vaccine, mFlusiva, that encodes for three HA proteins. Moderna tested vaccine candidates encoding HA and NA in humans, believing it could broaden protection, but paused development as part of its pipeline rethink.

GSK is advancing its investigational mRNA seasonal flu vaccine into Phase III, adding another contender to the nascent mRNA flu market just weeks after Moderna secured the first FDA approval for an mRNA-based flu shot. The UK drugmaker plans to begin the vaccine efficacy this month.The candidate, referred to as FLUm3HA.b-3NA, is designed to target both haemagglutinin (HA) and neuraminidase (NA), two primary surface antigens that cause flu viruses to bind and spread."Growing evidence suggests this could help improve protection, illness severity and transmission," the company said in a release Tuesday. "Previous studies highlighted the gaps in flu vaccination, including the role of NA and the need to improve B-strain HA immunogenicity."GSK said its candidate generated higher immune responses than licensed standard-dose and high-dose inactivated vaccines in younger and older adults, respectively, in Phase II testing.A mid-stage trial, called Flu-028, enrolled 971 adults, including people over 65, and tested a few of GSK's mRNA flu vaccine candidates — FLUm3HA.b-3NA, which encodes an optimised B-strain HA, and FLUm3HA-3NA, a non-optimised version of the same protein — against licensed age-appropriate comparators.According to GSK, its optimised FLUm3HA.b-3NA version triggered robust immune responses to HA and NA from influenza A and B strains in both younger and older adults, prompting the drugmaker to select that candidate for Phase III testing. Reactogenicity and safety profiles of the vaccines were also "acceptable," according to the company.The programme is entering a market that recently became more competitive. Moderna's mFlusiva was approved by the FDA in August for adults aged 50 and older, becoming the first mRNA seasonal influenza vaccine to reach the US market.However, it wasn't a smooth path toward approval. The FDA had initially refused to even review the application because it objected to Moderna's use of a standard-dose flu vaccine as the comparator for adults aged 65 and older, rather than a high-dose or otherwise enhanced vaccine recommended for that age group. The FDA eventually reversed course and the vaccine was ultimately approved after an advisory panel gave it a resounding thumbs up.