| Item 7.01. | Regulation FD Disclosure. |
On September 8, 2020, Spero Therapeutics, Inc. (the “Company”), in connection with the positive topline results for its Phase 3 ADAPT-PO clinical trial of oral tebipenem HBr described below, issued a press release (the “Topline Data Press Release”) and provided an investor presentation (the “Topline Data Investor Presentation”), which will be made available on the Company’s website or distributed by the Company in hardcopy or electronic form.
A copy of the Topline Data Investor Presentation and Topline Data Press Release are attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K (this “Current Report”). The information set forth in this Item 7.01 and in Exhibit 99.1 and Exhibit 99.2 attached hereto is “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall such information be deemed incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended.
Tebipenem HBr – Positive Topline Results from Phase 3 ADAPT-PO Clinical Trial
On September 8, 2020, the Company announced positive topline results for the Phase 3 ADAPT-PO clinical trial of oral tebipenem HBr in complicated urinary tract infection (“cUTI”) and acute pyelonephritis (“AP”). The ADAPT-PO trial is the first ever trial to compare an all oral regimen against an all intravenous (“IV”) regimen for the treatment of cUTI. The pivotal Phase 3 clinical trial of oral tebipenem HBr met the primary endpoint, demonstrating statistical non-inferiority versus IV ertapenem. The primary endpoint of the trial was defined as the overall response rate (combined clinical cure plus microbiological eradication) at the test-of-cure (“TOC”) visit in the microbiological-intent-to-treat population (“micro-ITT”). Favorable overall response rates at TOC were 58.8% versus 61.6% for tebipenem HBr and ertapenem, respectively (treatment difference, -3.3%; 95% confidence interval [CI]: -9.7, 3.2; -12.5% NI margin). Clinical cure rates at TOC were high, at greater than 93% in both treatment groups, and overall response rates were consistent across key subgroups of interest.
In the ADAPT-PO trial, comparative safety data from the 1,372 hospitalized adult patients who enrolled in the trial suggest that tebipenem HBr was well-tolerated, with a safety profile similar to that of ertapenem. Treatment emergent adverse events (“TEAEs”) were reported in approximately 26% of patients in both treatment groups. The most commonly reported TEAEs in both treatment groups were diarrhea (5.0%) and headache (3.8%). Serious TEAEs were infrequent (1.3% for tebipenem HBr versus 1.7% for ertapenem) and no deaths were reported in the trial. Three Clostridiodes difficile-associated TEAEs were observed in the ertapenem group, while none were observed in the tebipenem HBr group.
ADAPT-PO is a global, randomized, placebo-controlled Phase 3 clinical trial that evaluated the safety and efficacy of tebipenem HBr in hospitalized adult patients with cUTI or AP. Patients were randomized (1:1) to receive 600 mg of tebipenem HBr orally every 8 hours, or 1 g of ertapenem IV every 24 hours, for a total of 7 to 10 days. Patients with concurrent bacteremia received up to 14 days of therapy. The primary endpoint was the overall response, defined as the combination of clinical cure and microbiological eradication of the causative pathogen(s), at the TOC visit (Day 19, plus or minus 2 days) and was assessed in the micro-ITT population. The primary analysis and assessment of non-inferiority was evaluated using a pre-specified -12.5% non-inferiority (“NI”) margin. This NI margin was a modification of the original NI margin of -10% that was discussed with the U.S. Food and Drug Administration (“FDA”) because of concern that the COVID-19 pandemic could have an adverse effect on the trial. As a result, the NI margin was modified prior to database lock from the original NI margin. However, as noted by the lower bound of the 95% confidence interval (-9.7), the trial also achieved success according to the original -10% NI margin.
The Company plans to present emerging data from the tebipenem HBr program, including the ADAPT-PO clinical trial results, in detail at future scientific meetings and in publications. The Company intends to initiate a rolling New Drug Application (“NDA”) submission and anticipates completing the NDA submission to the FDA for tebipenem HBr in the second quarter of 2021.
