As the biopharma industry struggles to develop novel antibiotics Merck & Co has scored a notable pivotal study success with an antibacterial agent that is not an antibiotic but an antibody.
The group presented the data, along with progress of sorts with a more traditional antibiotic, at the ICAAC meeting in San Diego over the weekend. ICAAC might no longer be as important a conference in the biopharma calendar as it once was but, along with Merck, companies including Merlion, Cempra and Theravance also highlighted earlier-stage efforts to combat bacterial infections.
Among ICAAC-relevant stocks one of the biggest risers was Tetraphase, though it did not present at the conference. Its 16% climb on Friday was more likely a dead-cat bounce after the phase III failure of eravacycline caused the stock to plummet by 80% (End of an era for Tetraphase, September 9, 2015). Tetraphase’s travails in antibiotic development reflect those of the broader sector.
Merck is undeterred, as demonstrated by its presence at ICAAC, presenting what it said was a promising phase II result with relebactam, its beta-lactamase antibiotic, which it said warranted progress into phase III.
In 351 adults with complicated intra-abdominal infections relebactam showed that, when added to imipenem/cilastatin, it was no worse than imipenem/cilastatin alone. This might seem like faint praise, though it is relevant considering the growing threat of antibiotic resistance; relebactam aims to restore imipenem activity versus certain imipenem-resistant strains of Gram-negative bacteria.
Perhaps more impressive were Merck’s pivotal data at ICAAC with bezlotoxumab, for which the company now says it will seek approval in North America and Europe. This non-antibiotic project, an anti-toxin B MAb, specifically targets recurrence of Clostridium difficile, which the group says has no effective therapies.
In Modify I and II, two pivotal trials involving over 2,000 patients combined, a single bezlotoxumab infusion in addition to the standard of care significantly reduced C difficile infection recurrence compared with standard of care alone over 12 weeks.
Meanwhile, Merlion Pharmaceuticals, a private German group, reported a success with another beta-lactamase antibiotic, finafloxacin. In a phase II trial in 225 adults with complicated urinary tract infections and pyelonephritis a five-day course of finafloxacin yielded higher and faster microbiological eradication than twice-daily ciprofloxacin over 10 days.
Beyond these successes other biotech groups took the opportunity of ICAAC to highlight earlier-stage progress. Theravance Biopharma, for instance, said Vibativ, its marketed antibiotic against infections including MRSA, showed the greatest activity of all antibiotics evaluated against Gram-positive bacteria causing skin infections in US hospitals, though this came from in vitro data.
The group recently filed to expand Vibativ’s US label to include concurrent bacteraemia. If nothing else, progress with Theravance Biopharma’s antibiotic sheds more light on the group’s strategy since it was cleaved off from the original Theravance in 2013.
Elsewhere Cempra, a small-cap antibiotic player, used ICAAC to showcase its oral solithromycin, CEM-101, against various infections. And Ampliphi said its prototype bacteriophage cocktail showed comparable efficacy to vancomycin in a mouse model of Staphylococcus aureus lung infection.
Of course, it was not all good news at ICAAC, as Merck’s studies of bezlotoxumab also showed a fail for actoxumab, a related antitoxin, which provided no benefit over placebo in preventing C difficile recurrence.
It is fortunate for Merck that it has bezlotoxumab to fall back on. Merck is notable for being a big pharma company with a major focus on antibiotics and anti-infectives, and after its $9.5bn purchase of Cubist it has a lot to live up to.
|Bezlotoxumab||Merck & Co||Modify I||NCT01241552|
|Bezlotoxumab||Merck & Co||Modify II||NCT01513239|
|Relebactam||Merck & Co||–||NCT01506271|