Dive Brief:
- In a mixed bag of news for Achaogen, the Food and Drug Administration approved its once daily intravenous antibiotic Zemdri for complicated urinary tract infections caused by Enterobacteriaceae in patients with few or no alternative treatment options, but gave the company a thumbs down for bloodstream infection.
- The approval of the aminoglycoside is based in part on the Phase 3 EPIC cUTI trial, which showed non-inferiority to meropenem for the co-primary efficacy endpoints of composite cure (clinical cure and microbiological eradication) at day five and test-of-cure around day 17.
- The FDA also handed Achaogen a Complete Response Letter for Zemdri's submission for bloodstream infection, leading to a 20% drop in share price. The CRL said that the CARE study data wasn't sufficient to show effectiveness in this indication. Achaogen will meet with the FDA to attempt to resolve the issues.
Dive Insight:
Around three million cases of complex urinary tract infections (cUTIs), including pyelonephritis, are treated in hospitals in the U.S. every year. If not managed properly, treatment failure rates and recurrences increase, re-hospitalization numbers climb, patient outcomes worsen and healthcare costs balloon. Achaogen's aim is to provide an alternative option in the form of Zemdri (plazomicin), particularly for difficult-to-treat patients.
"Bacteria continue to circumvent existing antibiotics, making certain infections notoriously hard to treat and putting some patients at high risk for mortality," said James McKinnell, at the David Geffen School of Medicine and LA Biomed at Harbor-UCLA, in a company release.
The response from the FDA for Zemdri mirrored the Antimicrobial Drugs Advisory Committee advice in May, with a unanimous positive vote in support of the complicated urinary tract infection indication and an 11 to 4 negative vote against the bloodstream infection (BSI) indication, the potentially larger market. The share price fell around 25% at the time, and NASDAQ halted trading of the company's common stock.
"Voting members felt that while the CARE data was positive, the evidence did not meet the substantial requirement under the LPAD (limited population antifungal/bacteria drug) approval pathway. While there is no indication for BSI, the plazomicin label does include microbiological data… and [Leerink's expert network] MEDACorp physician feedback has reiterated their desire to have another antibiotic class treatment option for their carbapenem-resistant Enterobacteriaceae patients, given the few treatment options for these patients…" wrote Leerink analyst Ami Fadia in a note to investors.
Despite the positive spin from the company and its opinion leaders, the market showed its dismay again on the BSI news, with stock value dropping to close to its 52-week low, which surprised analysts.
"While investors might have become incrementally more optimistic in the week leading into the PDUFA, we are nevertheless surprised by the negative stock reaction today … particularly after the negative stock reaction following the May 3 AdCom vote," Fadia added.
Leerink predicts revenue for Zemdri of around $160 million in cUTI and $250 million in BSI by 2025, with a launch for cUTI expected in July 2018.
The FDA is among the agencies globally making efforts to combat antimicrobial resistance, with a statement from FDA Commissioner Scott Gottlieb earlier this month describing the the agency's work to improve economic incentives for companies developing antibiotics, make the development process more predictable, and support companies working in the area.