Sabizabulin has been shown to reduce deaths and ICU days for hospitalised patients at high risk of developing ARDS.
An oral covid treatment shown in a clinical trial to reduce deaths has been granted provisional determination by the TGA for use in hospitalised patients with moderate to severe infection.
The announcement paves the way for applicant Adjutor Healthcare to seek provisional registration of sabizabulin, a cytoskeleton disruptor developed by US biopharmaceutical company Veru.
The drug is specifically effective in treating covid patients at high risk of developing acute respiratory distress syndrome (ARDS) and becoming seriously ill.
It has a different mechanism of action from the other covid treatments provisionally approved by the TGA for use in Australia, including molnupiravir (Lagevrio), nirmatrelvir-ritonavir (Paxlovid) and remdesivir (Veklury).
Sabizabulin has been shown in preclinical models to have dual antiviral and anti-inflammatory properties, according to a study published in the NEJM in July.
Researchers conducted a randomised, multi-centre placebo-controlled phase III clinical trial with hospitalised patients who had moderate to severe covid and were at high risk for ARDS and death.
Published results from clinical trials on hospitalised patients with moderate-to-severe covid-19 showed significant reduction in hospital and ICU stays, requirement for mechanical ventilation or death compared to a placebo.
“Sabizabulin is an orally available, novel microtubule disruptor that targets, binds, and crosslinks both the alpha- and beta-tubulin subunits to inhibit polymerisation and to induce depolymerisation of microtubules in cells,” the authors of the NEJM article wrote.
“Microtubules are intracellular transport structures critical for coronavirus cellular entry, trafficking, replication, and egress as well as for triggering the innate inflammatory response and cytokine storm responsible for ARDS, septic shock, and frequently death.
“ARDS is one of the primary causes of mortality in covid-19 infection, as infiltration of immune cells in both lungs leads to alveolar-capillary membrane injury and oedema; increased lung permeability leads to exudates filling the air sacs, with resultant hypoxaemia. Preclinical studies demonstrate that sabizabulin has both significant antiviral and anti-inflammatory activities by disrupting microtubule dynamics.”
As part of the trial, 204 patients were randomly assigned to treatment: 134 to sabizabulin and 70 to placebo. Sabizabulin superiority was demonstrated by a planned interim analysis for the first 150 randomised patients, the authors reported.
The mortality rate was 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo.
For the key secondary end points, sabizabulin also reduced ICU days, days on mechanical ventilation and days in hospital versus placebo. Adverse and serious adverse events were lower in the sabizabulin group than the placebo group.
Internationally, the US Food and Drug Administration has received an Emergency Use Authorization application for sabizabulin and the UK Medicines and Healthcare Products Regulatory Agency is undertaking an expedited review.
In making its decision to grant Adjutor Healthcare a provisional determination, the TGA considered all eligibility criteria, including evidence of a plan to submit comprehensive clinical data and the seriousness of the pandemic.
Granting of the provisional determination precedes the market authorisation application and does not guarantee approval of that application.
Dr Rosalie Cull, CEO of Adjutor Healthcare, was contacted for this story, but she said she was unable to comment.
