Emphatic results from two phase III trials of Achaogen’s antibiotic plazomicin should pave the way for the approval of a new weapon in the fight against antimicrobial resistance. And, just as importantly for the company, the results might help it attract a buyer.
Achaogen’s share price shot up 148% yesterday, but with a market cap of $373m it is still fairly inexpensive, making it a prime candidate for a takeout. Who might acquire it is another question – Merck & Co’s takeover of Cubist in 2014 shrank the pool of antibiotic players. But there has been a resurgence of interest in the sector of late, with companies including Pfizer and Novartis pledging to tackle antimicrobial resistance this year.
Other big pharmas are getting in on the act, with Roche teaming up with Japan’s Meiji Seika Pharma and Canada’s Fedora Pharmaceuticals last year on a phase I project, OP0595, and Glaxosmithkline set to take its candidate gepotidacin into phase III. Antibiotics are back in vogue, and Achaogen’s results might have come at just the right time.
There is still the worry that any new antibiotics might be saved as a last resort to delay the emergence of resistance, which could limit their sales. But with governments dangling financial carrots to spur the development of new options, the sector is looking more attractive than it was a few years ago.
And if it does reach the market, plazomicin should be differentiated from other antibiotics, Sun Trust analysts believe. They pointed out several advantages: it is active against multiple strains of carbapenem-resistant enterobacteriaceae (CRE), can be given in a single 30-minute IV infusion per day, and can be combined with other agents for the treatment of infections caused by multiple pathogens.
The latest data from the phase III Epic and Care studies will not have hurt Achaogen’s cause. The company immediately cashed in, announcing a public offering of up to 5.75 million shares, worth $75m at yesterday’s price.
The funds are earmarked to support regulatory filings in the US in the second half of 2017 – plazomicin has priority review status so could be launched as early as 2018 – and in Europe in 2018.
Epic, a 609-patient registration trial in patients with complicated urinary tract infections (cUTI), met endpoints specified by both the FDA and EMA. To satisfy the former, plazomicin showed non-inferiority versus meropenem on a pre-specified composite endpoint of clinical cure and microbiological eradication; in addition, a test-of-cure analysis on the same primary endpoint suggested that plazomicin was superior to meropenem.
Meanwhile, plazomicin was superior to meropenem on microbiological eradication at the test-of-cure visit, as requested by the EMA. Meropenem is the gold standard of treatment for cUTI.
|Epic trial results|
|Plazomicin (%)||Meropenem (%)||Result|
|Composite endpoint at day 5, mMITT (FDA)||88.0||91.4||Statistical non-inferiority|
|Composite endpoint at TOC, mMITT (FDA)||81.7||70.1||Statistical superiority|
|Microbiological eradication at TOC, mMITT (EMA)||87.4||72.1||Statistical superiority|
|Microbiological eradication at TOC, ME (EMA)||90.5||76.6||Statistical superiority|
|ME = microbiologically evaluable; mMITT = microbiological modified intent-to-treat; TOC = test of cure.|
The smaller Care trial, in 69 patients with serious infections due to CRE, found a lower rate of mortality or serious disease-related complications with plazomicin versus colistin, one of the few remaining antibiotics for this indication.
However, the small sample size meant that no formal statistical hypothesis testing was performed.
|Care trial results|
|Plazomicin (%)||Colistin (%)||Relative reduction|
|Day 28 all-cause mortality or significant disease-related complications (primary endpoint)||23.5||50.0||53.0%|
|Day 28 all-cause mortality||11.8||40.0||70.5%|
Neither trial raised any serious safety worries, although there was a slightly higher incidence of renal function adverse events with plazomicin than with meropenem in Epic.
On safety plazomicin looks to have the advantage over another antibiotic, Cempra’s solithromycin, which is due an FDA decision December 27 and 28 for the oral and intravenous versions respectively (Panel nod gives Cempra little solace, November 7, 2016).
The trial results, and the growing antimicrobial resistance problem, make plazomicin’s approval look likely. Achaogen will be hoping that this is also enough to hook a buyer.