SURE1 and REASSURE Trials Paved Way for FDA Approval of Orlynvah

This discussion with Corey Fishman, CEO of Iterum Therapeutics, and Steven Aronin, MD, SVP of Clinical Development at Iterum, elaborated on the approval of Orlynvah for uncomplicated urinary tract infections (uUTIs). Their insights focused on the SURE1 and REASSURE trials, which compared Orlynvah to ciprofloxacin and augmentin, respectively, paving the way for its FDA approval.

The SURE1 trial demonstrated that Orlynvah was superior to ciprofloxacin in patients with infections caused by ciprofloxacin-resistant organisms. Although, the trial also revealed an unexpected outcome: Orlynvah did not show non-inferiority against ciprofloxacin in patients with susceptible organisms. Aronin noted, "What was unexpected was the other population, the population of patients who had a ciprofloxacin-susceptible organism. We did not show non-inferiority, and that was unexpected.”

The researchers attribute this anomaly to the differential impact of antibiotics on the bacterial flora in patients. “Cipro sticks around a long time,” explained Aronin. “Because it sticks around a lot longer than beta-lactam antibiotics like sulopenem, it has a longer effect on the bacteria that are not causing infection but are just sitting there.” This prolonged presence led to better outcomes in the 12-day follow-up, making ciprofloxacin appear more effective in some cases.

Elaborating on cipro, Fishman said, “The safety profile is a major concern, and it is no longer recommended as a first-line agent. There is a significant resistance issue with Cipro, primarily due to safety challenges. There are several severe issues that can arise, and for uncomplicated infections, both the FDA and EMA have stated that it no longer makes sense to use Cipro as a first-line treatment for uncomplicated infections like uUTIs.”

Recognizing the need for further evidence to prove Orlynvah safe and efficacious, the FDA required they conduct a second study. TheTo address the unexpected findings from the SURE1 trial, they set up the REASSURE trial compared Orlynvah to augmentin, confirmed Orlynvah's superiority in susceptible populations and established non-inferiority across the overall population. Fishman emphasized the importance of this approval for empiric therapy in community settings, particularly where options are limited.

“The overall population is crucial,” Aronin noted. “Patients who show up with symptoms of a UTI and have an abnormal urinalysis—they have a UTI, but you don't know the bugs yet. That's the treating doctor’s population. It's important for the treating doctor to understand that we're just as good as the other agents in this space.”

Fishman added, “This is a very different model than historical antibiotics. Most that have launched recently have a big component in the hospital, but in the community, primary care doctors are the main prescribers. This is where sulopen can be incredibly valuable for appropriate patients.”

Looking ahead, Iterum Therapeutics plans to seek a strategic partner for the launch of Orlynvah. Fishman stated, “Now that we have approval, we will renew those efforts to find a partner to work with us in some capacity. It’s not just about being an antibiotic company; it’s about who the physicians are that are currently in your call pattern.”

The team is optimistic about finding a partner who can effectively introduce Orlynvah to the market, targeting companies with products that are already prescribed by primary care physicians and specialists like urologists and OB-GYNs. “We’d love to do that sooner rather than later because we want to get this product on the market, treating patients and helping physicians with limited options,” Fishman concluded.

As excitement builds, Aronin remarked, “I just came back from the Infectious Disease Annual Conference in Los Angeles, and lots of doctors came up to me. They’re very excited about the prospect of this being available to treat their patients. Everybody's talking about stewardship, but they also understand there's an unmet need here.”

The approval of Orlynvah not only fills a critical gap in UTI treatment options but also represents a significant advancement in addressing antibiotic resistance, ultimately benefiting both physicians and patients.

Watch Part 1 of our interview here: FDA Approves Oral Sulopenem (Orlynvah) for Uncomplicated Urinary Tract Infections