Infex chases after Insmed with bronchiectasis trial win
Dr Peter Jackson, chief executive of Infex Therapeutics.
There is only one approved therapy for lung disease non-cystic fibrosis bronchiectasis (NCFB) in the US and Europe – Insmed's Brinsupri – but UK startup Infex Therapeutics is in hot pursuit.
Infex's RESP-X (INFEX702) drug candidate cleared a phase 2a trial involving NFCB patients whose lungs are colonised with the bacterium Pseudomonas aeruginosa (Pa), showing early signs of efficacy as well as meeting safety, pharmacokinetics, and immunogenicity targets.
NFCB is a highly debilitating condition in which the walls of the airways become thickened and damaged as a result of a cycle of inflammation and infections, leading to repeated exacerbations or attacks that require antibiotic treatment and can force patients to be hospitalised.
DPP1 inhibitor Brinsupri (brensocatib), given as a once-daily oral tablet, became the first therapy approved by the FDA for NFCB last year and has been tipped by Insmed as a potential $5 billion-a-year blockbuster. It has subsequently been cleared for marketing in the UK and EU.
The UK biotech said that anti-PcrV antibody RESP-X – which could be dosed by infusion once every three months – was safe and well-tolerated, showed no signs of immune response that could dampen its efficacy, and reduced exacerbation rates in Pa-positive NFCB patients.
Dr Peter Jackson, chief executive of Infex, said that the results are an "important milestone" for the company, which is based at the former AstraZeneca site in Alderley Park, Cheshire.
They also "offer hope for NCFB patients colonised with Pa, a population with significant unmet medical need and no approved preventative treatment options."
The study tested two doses of the antibody, which targets a structural protein in Pa that acts as a "molecular syringe," allowing the bacteria to inject toxins into cells, and is described as an "anti-virulence" therapy. According to Infex, there were no severe or life-threatening treatment-emergent adverse events (TEAEs) with the treatment, and no patients withdrew due to side effects.
RESP-X's half-life in the body was calculated at 28.8 days with the higher 10 mg/kg dose, which Infex said supports its plans for dosing four times a year. The company will now start talking to regulatory authorities about the design of a larger trial powered to demonstrate efficacy.
Other competitors are also lining up to challenge Brinsupri, meanwhile, including Boehringer Ingelheim and Chiesi/Haisco Pharma, which have rival DDP1 inhibitors (respectively verducatib and HSK31858) in late-stage clinical development.
Armata Pharma is taking a similar approach to Infex with AP-PA02 – a bacteriophage-based drug that targets Pa in phase 2 clinical testing – while other candidates in the pipeline include Sanofi's anti-IL-33 antibody itepekimab (phase 3) and Chiesi's human neutrophil elastase inhibitor CHF-633 (phase 2).
