June 11, 2020
Our dialogue with the FDA also included discussion of the development of SPR720 beyond the Phase 2a clinical trial. These subsequent studies will assess SPR720 as part of a combination regimen, with the primary assessment to be based on a clinical endpoint. As we advance towards an IND submission for SPR720 and the initiation of the Phase 2a clinical trial, we reflect on our optimism for the path forward for SPR720 and the hope that it could bring to patients in need.
Spero has been in the fortunate position to engage with and listen to patients, clinicians and members of regulatory agencies at gatherings like the recent FDA workshop and NTM conferences and in our offices (pre-COVID, of course).
What are we hearing?
A shift to management of NTM has important implications for trials. Our interactions with patients, clinicians, and the FDA has led us to a stepwise approach to efficiently develop NTM medicines:
Phase 2 matters: Show the drug does its job. Our recent FDA interaction reinforced our plans and timing for a Phase 2a clinical trial. We provided a detailed overview of our strategy for Phase 2a in a previous post. In short, we aim to show that SPR720, administered on its own, can deliver a favorable therapeutic outcome relative to placebo. Exhibiting good PK, safety, and tolerability in patients is also a major and necessary step toward building a SPR720 containing therapeutic regimen. The 28-day duration of our planned Phase 2a clinical trial balances fidelity of a biological signal and speed to that signal, along with patient safety. We will study SPR720 at doses of 500 mg and 1000 mg per day compared to placebo, and we will include a standard of care arm to ensure that our therapeutic measures and timing are valid.
Downstream: Regimen-based therapy, clinical outcome assessment, shorter studies consistent with a disease management paradigm. We believe that our interactions with the FDA demonstrate the agency’s support for our clinical development plans for SPR720 beyond Phase 2a. Namely, we continue to see an opportunity to study the effectiveness of SPR720 as part of a therapeutic combination regimen, either under an adaptive single study design, or with a Phase 2b standalone clinical trial followed by a Phase 3 clinical trial as a basis for approval. With the right SPR720 containing combination and the right study design, we see a pathway to potentially shorter endpoints for approval (6 months or shorter) focused on clinical outcomes that demonstrate an improvement in patient health and consistent with a disease management paradigm.
NTM patients desperately need new options; these options need to be applicable early in disease development, be easy to use, and have an acceptable tolerability profile. We are pleased with the dialogue we have had with patients, clinicians, and regulators to date on how best to deliver on this therapeutic profile. These interactions confirm our conceptions of the field and enable us to continue to build a pathway showing the unique qualities of SPR720 that suit the emerging treatment paradigm that emphasizes patient outcome over microbiological cure. This is a major opportunity for a product candidate such as SPR720 to show that, in this new paradigm, a safe, well-tolerated, easy to administer oral therapy can be a treatment of choice in non-treatment refractory patients. We are inspired by our patient colleagues and excited to continue on this stepwise journey.