FDA sets June date for latest review of Merck’s last-ditch antibiotic

The FDA has started a six-month priority review of Merck & Co/MSD’s triple antibiotic Recarbrio in a new indication, setting up a possible approval by 4 June.

The new indication for Recarbrio – a novel antibiotic combination – is for use of the drug in adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by Gram-negative infections.

The drug, a fixed-dose combination based on established antibiotic Primaxin (imipenem/cilastatin) with Merck’s novel beta-lactamase inhibitor relebactam, was first approved by the FDA for complicated urinary tract (UTI) and intra-abdominal infections (cIAI) last July.

As with most antibiotics used as rescue therapies for challenging infections, Recarbrio isn’t expected to become a big seller for Merck. After its approval for cIAI last year, analysts at Cowen & Co said they expected turnover to reach $50 million this year, and $150 million in 2024.

Its clinical significance far outweighs its commercial prospects however, as it provides another option for patients who are running out of treatment options.

Drugs in the carbapenem class like imipenem have become last-line treatments for a number of multidrug resistant (MDR) infections. The inclusion of relebactam in Recarbrio is designed to restore sensitivity to the carbapenem, providing a fallback therapy.

The US marketing application is based on the results of the phase 3 RESTORE-IMI 2 trial in adult patients with HABP/VABP, due for presentation at the ECCMID 2020 conference in April.

The trial showed that Recarbrio was comparable to piperacillin/tazobactam – a combination antibiotic used for many years to treat invasive bacterial pneumonias like HABP/VABP – when it came to clinical cure, microbiologic cure, and adverse reaction rates.

Recarbrio hasn’t been approved in Europe yet, but that could happen within the next few weeks, as last December, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the drug.

Unlike the FDA’s indication-specific approval, the EU regulator is reviewing a blanket indication for Recarbrio in hard-to-treat Gram-negative infections, caused by organisms like Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Merck is one of the few big pharma companies still investing in antibiotics research, and it also sells another antibiotic – Zerbaxa (ceftolozane/tazobactam) – for cIAI and HABP/VABP that it acquired along with Cubist Pharmaceuticals in 2014.

An exodus of big pharma companies from antibiotics R&D is one of the factors behind a new UK proposal for a new payment system for antibiotics that will see companies paid upfront for access to new antibiotics based on their value to the NHS, rather than the volume of medicines sold.