Achaogen got a mixed outcome from the FDA advisory committee meeting on its antibiotic plazomicin yesterday, with a vote in favor of approval for complicated urinary tract infections but against its use in bloodstream infections.
Shares in the biotech were suspended yesterday in anticipation of the panel meeting but plummeted more than 26% premarket as investors reacted to the news and the potentially truncated commercial opportunity for the drug.
The cUTI indication gives Achaogen a clear route to approval with the panel voting 15 to 0 that the safety and efficacy of the antibiotic have been proven, and the biotech says there is still a chance that it can win over the FDA for bloodstream infections as well, despite a 4 to 11 vote in the other direction.
Specifically, Achaogen thinks the regulatory pathway for limited-population antibacterial drugs (LPAD), under which the FDA is reviewing the drug, enables it to “consider the benefits and risks for the sickest patients who have few or no available treatment options,” according to the biotech’s chief executive Blake Wise, who replaced Kenneth Hillan as CEO last December.
Plazomicin is the first drug to be evaluated using the pathway, which is designed to make it easier for companies to get approval for new antibiotics.
In briefing documents posted ahead of the meeting, the FDA reviewers acknowledged the difficulties faced by Achaogen in recruiting enough patients for its BSI trial, which was originally also intended to test the antibiotic in hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The small sample size meant that no statistical analysis was possible although the FDA noted “numerical trends” in favour of plazomicin on the primary endpoint of mortality due to any cause at 28 days.
“Antibiotics like plazomicin, … we believe, have the potential to address these limited patient populations,” says Wise. The company will not have to wait too long to hear of the FDA agrees with that assessment, as the agency is due to deliver its verdict on June 25.
Analysts at Leerink and Stifel both suggested plazomicin could still be used off-label in this indication even if the FDA turns it down, according to an EP Vantage report.
Plazomicin is a next-generation aminoglycoside developed with the aim of tackling multidrug resistant (MDR) Gram-negative pathogens such as carbapenem-resistant Enterobacteriaceae (CRE) that are becoming a huge problem for health systems around the world, leading to prolonged hospital stays and escalating costs of patient care.
Despite a chronic lack of R&D into new anti-infectives in recent years, there have been some encouraging signs that the biopharma pipeline is starting to kick into action once again.
In February, Allergan won a new FDA approval for Avycaz (ceftazidime/avibactam) which made it the first new drug to treat pneumonia caused by Gram-negative bacterial infections in the US in more than 15 years. The drug has been sold for complicated intra-abdominal and urinary tract infections in the U.S. since 2015.
Meanwhile, Merck & Co recently reported positive late-stage clinical results for a combination of its well-established Primaxin (imipenem/cilastatin) drug with new beta-lactamase inhibitor relebactam, outperforming Primaxin plus colistin, which is one of the few remaining antibiotics for treatment of CRE infections but has serious toxicity issues.
The adcomm discussion yesterday “underscored the real-world challenges that healthcare providers face every day given limited or inadequate treatment options for certain pathogens,” said Wise.