Liver toxicity concerns spike Motif Bio’s iclaprim filing

Motif Bio’s hope of adding to the antibiotic armamentarium for serious bacterial infections has just been dealt a blow by the FDA.

The company says the regulator has rejected its marketing application for iclaprim as a treatment for acute bacterial skin and skin structure infections (ABSSSI) as it needs “additional data … to further evaluate the risk for liver toxicity before [it] can be approved.”

London-headquartered Motif put a brave face on the outcome but has been brutalized by the news, with its shares falling 84% in trading on the GBX exchange to enter penny share territory, matched by an 80% decline on the Nasdaq.

It’s a case of déjà vu for iclaprim, which was first brought in front of the FDA in 2009 when it was owned by Arpida but was turned down with a request for another clinical trial.

The company is obviously disappointed by the decision, but analysts at Peel Hunt say it has come as a real surprise given that iclaprim showed an “extremely favorable” safety and toxicity profile established through testing in around 1,300 patients, and the FDA didn’t schedule an advisory committee to go through the data before making a decision.

The verdict leaves “no clear route to approval or commercialization,” they suggest, and in the meantime Motif’s cash reserves are starting to look a little light at around $12 million in cash—and $15 million in debt—as of the end of 2018.

The company’s CEO Graham Lumsden said the next step is to request a meeting with the FDA to discuss the Complete Response Letter (CRL) for the program, which should take place “within approximately 30-45 days.”

“We look forward to working with the agency to discuss options to advance iclaprim towards approval,” he added.

Iclaprim—which Motif described as a next-generation diaminopyrimidine—is the company’s only clinical-stage program. It has been planning trials in follow-up indications including hospital-acquired bacterial pneumonia and Staphylococcus aureus infections in people with cystic fibrosis.

The drug hit the mark in two separate ABSSSI phase 3 trials, matching antibiotic mainstay vancomycin which is starting to be affected by drug resistance and also carries the risk of kidney toxicity.

The company has previously said that one of iclaprim’s main advantages over vancomycin was its lack of kidney problems, given that around one-fourth of the 3.6 million ABSSSI patients admitted to U.S. hospitals each year has kidney disease.