EMA headquarters, Amsterdam

DUBLIN – Johnson & Johnson’s Janssen Biotech arm is on the brink of a historic first vaccine approval, having secured a positive vote May 29 from the EMA’s Committee for Medicinal Products for Human Use (CHMP) for its prime-boost Ebola virus vaccine combo, Zabdeno (Ad26.Zebov) plus MVABEA (MVA-BN-Filo). The CHMP also voted through applications for a first-in-class antiviral drug, a first-in-class antibiotic and two cancer drugs at its monthly meeting this week.

J&J’s imminent approval – formal marketing authorization from the European Commission will follow in August – also signifies the first ever licensure of an adenovirus type 26 (Ad26) recombinant viral vector. The second component of the vaccine, which comprises a recombinant modified vaccinia Ankara vector (MVA), comes from Copenhagen, Denmark-based Bavarian Nordic A/S. It represents the second approval for the platform in less than a year – Bavarian’s smallpox vaccine, Jynneos (smallpox and monkeypox vaccine, live, non-replicating), gained FDA approval last year.

Ad26 is part of the Advac technology, which J&J, of New Brunswick, N.J., gained through its $2.4 billion acquisition of the Dutch firm vaccine developer Crucell almost a decade ago. The approval is an important milestone in the evolution of the Advac platform, which also underpins J&J’s COVID-19 vaccine development efforts. It comprises a series of recombinant adenovirus vectors, whose naturally occurring counterparts have low seroprevalence in the general population, which should minimize the risk of pre-existing antibodies undermining the vaccine’s efficacy.

That general issue was aired in the past week, when the first clinical data from a COVID-19 vaccine candidate, Ad5-nCoV, an Ad5-based vector expressing the SARS-CoV-2 spike glycoprotein, were published in The Lancet, May 22, by a team from Shanghai-based Cansino Biologics Inc., and clinical collaborators. The vaccine was able to elicit the production of neutralizing antibodies in about half of the healthy volunteers who received what was deemed to be highest safe dose tested, though its immunogenicity was impaired by the presence of pre-existing antibodies in about half of the phase I trial participants.

Meanwhile, Myr GmbH, of Burgwedel, Germany, is set to gain a conditional marketing authorization for Hepcludex (bulevirtide), a first-in-class viral entry inhibitor it developed for treating chronic hepatitis delta virus (HDV) infection in individuals with compensated liver disease. HDV is a defective RNA virus that requires co-infection with HBV for replication – it occurs in about 5% of HBV patients worldwide. Hepcludex, which has orphan drug designation, targets sodium taurocholate co-transporting polypeptide, a liver bile salt transporter receptor that promotes entry of both viruses into hepatocytes. It also prevents trafficking of the viral genome to the nucleus. Myr’s development program had received Prime designation from the EMA. The same drug, which, should it gain FDA approval, will be branded Myrcludex in the U.S., where it has received breakthrough therapy designation from the FDA.

Dublin-based Nabriva Therapeutics plc is also in line for its first European approval, for Xenleta (lefamulin), a first-in-class pleuromutilin antibiotic for treating community-acquired bacterial pneumonia in adults. The assessment was based on two phase III trials, Leap 1 and Leap 2, in which Xenleta achieved noninferiority as compared with the standard-of-care treatment moxifloxacin. According to pooled data from the two studies, in 1,242 participants, Xenleta attained a test-of-cure success rate of 88.5% in the clinically evaluable population as compared with 91.8% for those on moxifloxacin. The drug gained FDA approval last August. The company’s stock (NASDAQ:NBRV) rose 33.9% to close May 29 at $1.14.

Basel, Switzerland-based Roche Holding AG gained a recommendation for approval for Rozlytrek (entrectinib) for treating adults and pediatric patients older than 12 with any solid tumor harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion and for treating adult patients with ROS1-positive non-small-cell lung cancer who have not previously received ROS1 inhibitors. The same drug gained FDA approval last August.

Basel-based Novartis AG secured a positive vote for Piqray (alpelisib) in locally advanced or metastatic hormone-receptor-positive, HER2-negative breast cancers that carry a PIK3CA (phosphatidylyinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) mutation. Piqray, a PIK3 inhibitor, secured the recommendation on the basis of the phase III Solar-1 trial, in which a combination of Piqray plus the estrogen receptor inhibitor fulvestrant almost doubled progression-free survival as compared with fulvestrant monotherapy (11 months vs. 5.7 months; p<0.001). The same drug gained FDA approval 12 months ago.

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