Innoviva’s ‘game changer’ antibiotic tackles gonorrhoea

GARDP's Dr Manica Balasegaram

Dr Manica Balasegaram, executive director of GARDP

Innoviva has moved a step closer to bringing the first novel antibiotic to market for gonorrhoea in decades after reporting positive results in a phase 3 trial.

An oral dose of zoliflodacin – vying to become the first in the new class of bacterial type II topoisomerase inhibitors – was found to be as effective as the standard regimen of injectable ceftriaxone and oral azithromycin in resolving uncomplicated Neisseria gonorrhoeae infections.

Uncomplicated gonorrhoea infections have a high level of morbidity, enhance the transmission of other sexually transmitted diseases, and are highly stigmatised, often causing shame and affecting personal relationships.

In the 930-patient trial, a single dose of zoliflodacin was found to be non-inferior to the standard regimen at achieving microbiological cure at the urogenital site of infection and was well-tolerated, with no serious adverse events or deaths in the study. It recruited men, women, adolescents, and people living with HIV, and is said to be the largest trial in uncomplicated gonorrhoea ever undertaken.

Innoviva is developing zoliflodacin in partnership with the Global Antibiotic Research & Development Partnership (GARDP), a non-profit consortium, in what it said was “a new research and development model in the global fight against antimicrobial resistance (AMR).”

Gonorrhoea was diagnosed in 82 million people in 2020 and, according to World Health Organization (WHO) estimates, ranks high among the agency’s infectious diseases of greatest concern, as it is rapidly becoming resistant to antimicrobial medicines.

In the US alone, case numbers increased 118% between 2009 and 2021, to reach more than 710,000 - an alarming increase, given that some so-called ‘super-gonorrhoea’ infections have become untreatable with all seven main antibiotic classes. Ceftriaxone, given as a single intramuscular injection, has become the last available recommended treatment for gonorrhoea globally.

Zoliflodacin was originally developed by AstraZeneca and its spin-off company Entasis Therapeutics, but had been sidelined by the company – despite a positive phase 2 trial – until the GARDP stepped in to provide funding for a phase 3 programme in 2019.

Innoviva subsequently inherited the programme when it acquired Entasis in a $113 million deal last year.

“Despite the extremely high public health value, there has been a lack of investment to develop new drugs for gonorrhoea,” commented Dr Manica Balasegaram, executive director of GARDP, which has rights to the novel antibiotic in around 130 counties worldwide.

“This is a significant step forwards in the treatment of gonorrhoea, and also shows that GARDP’s public-private partnership model can play a crucial role in helping to fix the public health failure at the heart of the global AMR crisis,” he added.

Previous in vitro studies have shown that zoliflodacin is active against multidrug-resistant strains of N. gonorrhoeae, including those resistant to ceftriaxone and azithromycin, with no cross-resistance with other antibiotics.

The question now is how the drug might be used in practice if approved. New antibiotics are typically reserved as last-line therapies, used sparingly to try to prevent the development of resistance, which prevents widespread use – something that has made the field unattractive for pharma companies, which have deserted R&D into new antimicrobials in drives in the last couple of decades.

Innoviva has already benefitted from one attempt to develop a new business model, pioneered by the UK, which involves an annual subscription payment for access to drugs, regardless of how much may be used in practice.