August 11, 2020
We designed a Phase 3 trial comparing oral tebipenem HBr head-to-head with IV ertapenem to demonstrate that an oral carbapenem has the potential to be a more attractive treatment option than an IV carbapenem. If our Phase 3 trial yields positive data, we believe it would demonstrate that oral tebipenem HBr could offer the equivalent efficacy of IV ertapenem while providing the potential to keep RRF UTI patients out of the hospital.
Well before COVID-19, healthcare stakeholders have demonstrated a concerted effort to get patients out of the hospital quickly or to keep patients out of the hospital entirely, when possible. Surgeons, for example, keep a close watch on their length of stay metrics and have implemented rapid recovery protocols to speed hospital discharge after surgery. Some fairly intensive surgical procedures, like joint replacements, are being performed in ambulatory surgery centers to avoid hospitalization altogether. Similarly, Emergency Departments routinely utilize observation units for stays expected to be less than 24 hours. Further, stemming back to the 1970s, we have seen the growth of the Urgent Care model to triage non-life-threatening emergencies. Treating patients in the lowest acuity setting possible has many potential benefits, including patient safety and patient quality of life factors.
Much as COVID-19 has accelerated trends such as grocery delivery, the added risk and burden that COVID-19 has placed on the healthcare system has accelerated the shift to treat even serious illnesses outside of the hospital. A New York Times headline dated April 6, 2020 asked, “Where Have All the Heart Attacks Gone?”1 The Washington Post, covering the same topic, noted on April 19, 2020 that patients with heart attacks, strokes and even appendicitis had essentially vanished from hospitals.2 The absence of care for these severe patients is a concerning yet real consequence of COVID-19.3 The data suggest that as the pandemic continues, many specialties will continue to defer inpatient procedures and use technology to defer or avoid in-person visits after the “new normal” is established. For example, telehealth was up 3,500% over baseline at the first pandemic peak with a shift in severity of conditions treated by telehealth.4,5
When fluoroquinolones were introduced in the 1980s, they enabled cUTI to be treated effectively at home. Despite the push toward treatment in lower acuity settings and the availability of powerful oral agents, there was a 56% population-adjusted increase in hospitalization for UTI over the decade from 1999-2011.6 More recent data show that one in three UTI admissions is due to a resistant pathogen (ESBL or FQ-resistant) and that these patients are not necessarily sicker than patients with organisms that are susceptible to orals.7 While 86% of UTI patients in the community can be treated outside of the hospital, there are over a million cases annually that cannot be addressed with the current arsenal of oral antibiotics and require IV therapy.7 So today, while complex surgery can be performed outside of the hospital, RRF UTI patients frequently require hospitalization. This paradigm is broken.
Outpatient utilization of IV ertapenem has grown to nearly 60% as of 2018, while only about 40% of IV ertapenem usage is in the hospital, the lines having crossed in mid-2015.8 Further, in a recent Spero-sponsored market research study, community physicians reported stocking ertapenem in their clinics for intramuscular injection as a way to help patients with resistant UTI avoid hospitalization.7 Unfortunately, outpatient utilization of IV-administered therapies has a 25% complication rate, which ultimately results in the patient being hospitalized as a result of the IV administration, not the underlying disease. Moreover, it is well documented that patients prefer the convenience and lack of invasiveness of oral therapy over IV administration.9
In the last few years, several clinical trials have demonstrated that with oral potency equal to IV, transition to outpatient oral therapy is appropriate for serious infections such as endocarditis, osteomyelitis and Enterobacteriaceaebacteremia.10-12 Spero has raised the bar higher. We carefully designed our Phase 3 ADAPT-PO trial to compare oral tebipenem HBr directly against IV ertapenem in a serious infection without an IV lead-in. In demonstrating oral equivalence to IV, tebipenem HBr has the potential to be the only oral carbapenem that can provide the confidence of an IV and hence the ability to treat patients completely at home without the need to have them set foot in the hospital. The overall result of an effective oral agent not only is preferable to patients, but again reduces the burden on the healthcare system and minimizes safety risks to patients when IV therapy is involved, and even more so when IV therapy is administered within the confines of a hospital setting.
IQVIA findings from qualitative research with physicians showed that as a result of COVID-19 community physicians were generally more likely to prescribe an oral or self-injectable medication for their patients when possible (disease-state agnostic; e.g., PCPs were 50% more likely).5 We know that it can be clinically appropriate to treat UTI patients who do not require hospitalization at home. Likewise, there are significant economic savings associated with hospital avoidance and reduced patient lengths of stay. For patients that are out of oral options for cUTI, if FDA approved, tebipenem HBr could make at-home treatment possible once again. This is a value that resonates powerfully with patients and providers, particularly in the new normal of COVID-19.