Xav-19 (Xenothera) is a treatment for moderate lung damage due to COVID-19 in hospitalized adult patients. The High Authority of Health refused his authorization. The French laboratory has announced the continuation of the development of its drug. What is this treatment? Is it effective against Omicron? When in France?
The French laboratory Xenothera announced on January 31 in a communicated the further development of its anti-SARS-CoV-2 antibody, the Xav-19 treatment. In one review published on January 28, 2022, the Haute Autorité de Santé (HAS) refused post-MA early access authorization (marketing authorisation) to the treatment Xav-19 (Xenothera) in the indication of “treatment of moderate lung damage due to COVID-19 in hospitalized adult patients, with a NEWS score < 5, requiring low-flow oxygen therapy not exceeding 4L/min“. ANSM concluded that “the efficacy and safety of this medicinal product in the indication considered were not strongly presumed.”
Definition: what is the Xav-19 treatment?
The XAV-19 is a treatment dedicated to patients with moderate COVID-19, and expected to reduce the rate of respiratory aggravation, block the transition to severe form, and in particular avoid transfer to intensive care. “The XAV-19 is a porcine glyco-humanized neutralizing polyclonal antibody raised against the RBD protein of the original Wuhan strain of SARS-CoV-2“according to the lab.
Why do ANSM and HAS refuse XAV-19?
HAS issued a refusal on January 28 at the request of Xenothera for its product Xav-19. According to the ANSM, “on a clinical level, in view of the data transmitted in the initial file and the additional data transmitted following the requests for information made by the HAS, no objective element to date demonstrates the therapeutic benefit of Xav-19 in the indication claimed by the company and according to the proposed dosage schedule. […] The Polycor clinical trial failed to demonstrate that Xav-19 reduced the risk of respiratory failure at D15 for patients included in the trial in the ITT population or in the “NEXS score less than 5” subgroup presented as a population of interest by the laboratory. From additional data is therefore necessary to objectify the interest of this processing in moderate lung damage due to Covid-19 in hospitalized adult patients, with a NEWS score <5, requiring low-flow oxygen therapy not exceeding 4L/min".
What are the results published by Xenothera?
“Our results demonstrate that XAV-19 can completely neutralize all variants of SARS-CoV-2” indicate the authors of the studies carried out by Xenothera in November 2021.”XAV-19 is a porcine glyco-humanized polyclonal neutralizing antibody against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. […] In Spike/ACE-2 interaction tests, XAV-19 showed potent neutralization capabilities of the original Wuhan Spike and variants British (Alpha/B.1.1.7) and South African (Beta/B.1.351).[…] the viral load reduction potential in the lungs has been confirmed in a mouse model human transduced by ACE-2. XAV-19 is currently being evaluated in patients hospitalized with moderate COVID-19-induced pneumonia in phase 2a-2b (NCT04453384) where safety has already been demonstrated and in an ongoing 2/3 trial (NCT04928430) to assess the efficacy and safety of XAV-19 in patients with moderate to severe COVID-19. Due to its polyclonal nature and glyco-humanization, XAV-19 can provide a new safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19), including the different variants concerns identified so far” according to data published on November 15, 2021.
Is Xav-19 effective against Omicron?
“The analyzes carried out demonstrate that XAV-19, already active on the previous variants, has the ability to block Omicron” announced Xenothera in a communicated on December 27, 2021.”We have known since last week that the monoclonal antibodies currently used as treatment lose their therapeutic activity on the Omicron variant. In this context, our results bring a glimmer of hope to combat this new variant. The loss of effectiveness of monoclonal antibodies is not really a surprise. Since XAV-19 is a polyclonal antibody, its effectiveness against variants is systematically probable, even if it still needs to be verified and this is what we have just done..” said Odile Duvaux, President of Xenothera.
Sources:
“Anti-Covid XAV-19 treatment: biotech XENOTHERA announces the continued development of its anti-SARS-CoV-2 antibody“, Xenothera press release, January 31, 2022
Decision n° 2022.0029/DC/SEM of January 27, 2022 of the College of the High Authority for Health refusing the request for early access authorization for the XAV-19,HAS specialty, posted online on January 28, 2022
“XAV-19, a porcine glyco-humanized polyclonal antibody against the spike receptor binding domain of SARS-CoV-2, targets multiple epitopes and broadly neutralizes variants“, Frontiers in Immunology, November 15, 2021