February 26th, 2020
Our discussions with each of these key stakeholders highlight the importance of a robust clinical trial to support the clinical and commercial uptake potential of a new oral agent. The trial must instill confidence among patients, physicians and payors that an oral agent can replace the intravenous (IV) standard of care. Furthermore, equivalence to the IV standard of care must be shown in patients representing the target population, which for tebipenem HBr are patients that have resistance to other oral antibiotics. Below we explore why an oral-only trial, comparing an oral therapy head-to-head against the standard of care IV therapy, is the optimal trial design to meet these requirements and, if successful, best prepare a medicine for potential clinical and commercial success.
Despite a growing unmet need for more powerful oral anti-infectives for the treatment of cUTI (see blog post here for a review), drug developers have not been able to deliver one for more than three decades. While a successful Phase 3 result for any oral medication treating cUTI would represent an advance, not all trials are created equal. Prior trials (and several current trials) have utilized the lead-in of an IV therapy prior to the initiation of oral therapy; in part, this trial design is based on the belief that using an IV lead-in allows for the IV-administered candidate to do the heavy burden of treating the infection when the bacterial load is highest because the orally administered candidate is unable to demonstrate effectiveness from the start. However, such a design creates ambiguity as to the true power of the oral therapy to deliver on its value proposition to payors and clinicians – effective replacement of an IV therapy with an oral therapy. An oral-only trial can provide the necessary evidence without confounding elements.
A medicine’s ability to yield high drug exposures and ultimately a successful clinical trial versus current standard of care treatment in the population of interest can have a positive impact on its clinical and ultimately commercial success. Examples abound of the power of clinical evidence in uptake, as demonstrated by oral-only trials for fluroquinolones that were key to their early and sustained adoption. Healthcare providers, payors and patients all have a unified goal in ensuring a positive outcome; however, for the manufacturers it is often difficult to marry and unify the goals of all three in a single trial.
Bottomline, it is important to provide a strong clinical and economic rationale for any new medicine introduced to drive early and sustained uptake. The stronger the evidence regarding the medicine’s value proposition (clinical and economical), the higher the odds of a faster and sustained uptake and adoption by payors and clinicians.
Given the documented benefits of an oral-only trial design, why don’t all drug developers use this design? High drug exposures are key to being able to deliver successfully in this design, and not all agents reach sufficient exposures in the plasma to do so. Spero has very carefully selected its Phase 3 dose to be able to answer this fundamental question (see our blog post here for more details) and it benefits from the superior bioavailability of tebipenem HBr. Good drug exposure is the key to delivering a successful trial and ultimately a strong value proposition; in the absence of sufficient exposure, a drug developer is forced to consider less compelling study designs.