Statement of Dr. Diana Zuckerman
At the FDA Antimicrobial Drugs Advisory Committee Meeting on Sulopenem
September 9, 2024
I’m Dr. Diana Zuckerman, president of the National Center for Health Research. Our center is a nonprofit public health think tank that scrutinizes the safety and effectiveness of medical products, and we don’t accept funding from companies that make those products — so we have no conflicts of interest.
Thank you for the opportunity to share my views today and thank you for the important work of this Advisory Committee. My expertise is based on my current work as well as my post-doc training in epidemiology and public health, and as a former faculty member and researcher at Yale and Harvard. I’ve also previously served as professional staff in the US Congress, HHS, and the White House. I’m a founding Board member of the nonprofit Alliance for a Stronger FDA, which educates Congress about the need to financially support the essential work of the FDA.
Antibiotic resistance is clearly a serious problem, so we need to take today’s meeting very seriously. As a woman, I am very familiar with UTIs and know that they are very common and can interfere with daily life. However, UTIs are an acute illness with very obvious symptoms, so research on a medication for UTIs should focus on patient-centered symptoms and outcomes, not the bacteria in the urine of asymptomatic women who have already been treated. A composite measure does not make sense. FDA usually relies on surrogate endpoints when the clinical endpoint would take years to study. Surrogate endpoints are a way to complete studies more quickly, such as a surrogate endpoint that predicts if a drug reduces the chances of long-term disability or death. But since UTI is an acute illness, we don’t need a surrogate endpoint for an uncomplicated UTI: All that matters is that the infection does not progress and the symptoms go away. We know if the UTI symptoms have disappeared in a week or at most a few weeks.
As panel members have stated, there can be bacteria in the urine of asymptomatic women that do not affect a woman’s health. In fact, research shows that giving antibiotics to asymptomatic women can result in more symptomatic urinary tract infections. Bacteria in urine may show which patients are more likely to get another UTI but is not proven to predict whether a particular antibiotic makes a recurrence less likely – because some patients are more likely to have a recurrence than others, regardless of
what antibiotic they use.
Most important: an uncomplicated UTI is not life-threatening – if antibiotic treatment is delayed for a week or two, it will still be successful. Meanwhile, drinking plenty of fluids, avoiding alcohol, swimming and baths, and other behavior changes can be helpful, and in some cases UTIs even go away by themselves. And there are other antibiotic choices for patients like those studied in these trials, so there is no urgent need to approve a new treatment that hasn’t been adequately proven to have long-term benefits compared to amoxicillin or Cipro for a UTI.
Doctors don’t order urine cultures for patients whose symptoms go away after treatment for UTIs, so measuring urine cultures after treatment has no relevance to the practice of medicine in the real world.
Cipro can have serious side effects, so an alternative to Cipro would be welcome if it were as effective as Cipro but was safer. But serious risks of Cipro were not known when it was first approved and it took years of Cipro being taken by large number of patients to determine those risks. The studies of sulopenem are much too small and short-term to determine what rare, serious long-term complications may be and whether it is as safe as Cipro. We do know that it is more likely to have side effects that are as unpleasant as UTI symptoms.
In summary, as several of you have pointed out today, there are problems with these studies. The patients studied by the sponsors were not necessarily the patients who you might be appropriate to use this drug — patients most likely to have a UTI that will not adequately respond to other antibiotics. If the drug is intended for those patients, it should have been studied on those patients. These different patient characteristics
mean we cannot know from the studies presented here whether this drug would be safe and effective in patients who most need it.
One last point: This should not be a first line treatment!