Novartis spinoff Nabriva finally scores its first antibiotic approval
In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.
The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.
It is the first new class of antibiotics for pneumonia in nearly two decades in the United States, chief Ted Schroeder suggested in an interview with Endpoints News ahead of the approval.
In 2017, the first pivotal trial showed lefamulin was as effective as moxifloxacin, which belongs to a family of broad-spectrum, systemic antibacterial agents that have been used widely as therapy of respiratory and urinary tract infections called fluoroquinolones.
In 2018, the FDA revised its guidance on fluoroquinolones, acknowledging their use has been associated with mental health side effects and serious blood sugar disturbances.
Last year, the second Nabriva trial also showed that lefamulin was as effective as moxifloxacin — although investors were concerned by the drug’s side-effect profile as cases of diarrhea were worse on the lefamulin arm, versus in patients given moxi.
On Monday, Nabriva said it expects to launch its drug, via major specialty distributors, next month. It will carry a list price of $205 for the IV version, per day — while the oral formulation is priced at $275 per day.
The lowest price for the most common version of moxifloxacin is around $27.00, about a 74% discount to the average retail price of $106.46, according to GoodRx estimates.
Lefamulin will have an edge because it is available in an oral formulation — most products launched today are IV only or principally designed for use in a hospital, Schroeder said. “(W)e actually think that this is really the outpatient opportunity, that will be the big driver, ultimately, of…sales.”
The company $NBRV did not provide its sales expectations for the drug, which is to be branded as Xenleta. But H.C. Wainwright analysts projected peak sales of $460 million through 2028 in a note published last week.
The beleaguered field of antibiotics is desperate for a winner. For one of the biggest threats to global health, the lion’s share of antibiotic development is taking place in a handful of labs of small biopharma companies as a majority of their larger counterparts focus on more lucrative endeavors. In recent months, a handful of antibiotic developers — including Achaogen and Tetraphase — have seen their value go up in smoke as feeble drug sales frustrate growth. But on average, most freshly approved antibiotics have been more potent versions of existing classes of antibiotics.
It is no secret that the industry players contributing to the arsenal of antimicrobials are fast dwindling. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments must be priced cheaply, and often lose potency over time as microbes grow resistant to them. Consequently, until now there have been no new class of antibiotics approved since the 1980s — and today, roughly 700,000 deaths annually are attributed to drug-resistant bacteria, according to the WHO.
“Right now, if we don’t do something to support the small companies that have the innovative products, we run a real risk of not only companies going bankrupt — but losing the antibiotic development expertise that’s resonant within those companies, because the scientists tend to move on and do other things,” Schroeder emphasized.
Weeks ago, the CMS unveiled a proposal to restructure the payment apparatus to rescue existing antibiotic manufacturers, by classifying drug resistance in a way will compel higher payments to hospitals treating patients with antimicrobial resistance, and crafting a pathway for doctors to prescribe appropriate new antibiotics without disrupting hospital budgets.
It’s a big step in the right direction, Schroeder said. “Antibiotic stewardship relies on using the appropriate antibiotics for the appropriate patient at the right time. And when cost is the first decision point, it kind of undermines the opportunity, undermines the principles of good antibiotic stewardship.”
He also expressed his support for the DISARM (Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms) legislation that is currently being considered by Congress. The bill is designed to compel reimbursement by Medicare of antibiotics that treat stubborn infections away from the bundled payment system, within which all antibiotics currently reside. “I think ultimately, that’s the best solution,” Schroeder said.
In May, Nabriva’s complicated urinary tract infection drug, Contepo, was spurned by the FDA, which cited issues related to facility inspections and manufacturing deficiencies at one of Nabriva’s contract manufacturers. Lefamulin’s manufacturing apparatus is completely separate, Schroeder added.