Item 8.01 Other Events.
On June 10, 2022, Fulcrum Therapeutics, Inc., or Fulcrum, announced clinical proof-of-concept data from the ongoing Phase 1b trial of FTX-6058 for the treatment of sickle cell disease, or SCD. Initial data from the first subjects to receive a 6 mg dose of FTX-6058, an oral fetal hemoglobin, or HbF, inducer, showed a rapid and robust induction of HbF and achieved increases of up to 6.3% over baseline, were increasing at last measured time point, and that maximal levels of HbF may have not yet been achieved.
Increases in HbF have been shown to reduce the frequency or severity of a broad range of SCD symptoms, including vaso-occlusive crises, or VOC, anemia, pain, infection, stroke and others. Based on a large body of genetic, clinical, and observational evidence showing the effects of higher levels of HbF in people with SCD, the induction of HbF by 5-10% over baseline could be associated with reduced disease burden and improved clinical outcomes. These initial data showing that FTX-6058 increases HbF levels by up to 6.3% support its potential to become a transformative therapy for people living with SCD.
The Phase 1b study has enrolled six of up to ten subjects. These six subjects (none on background hydroxyurea) received at least one 6 mg dose of FTX-6058 and all were included in the safety analyses. As of the data cut-off on May 25, 2022, three subjects were evaluable at day 28 and beyond for increases in HbF. Three subjects were not evaluated due to non-adherence or protocol deviation, as specified in the statistical analysis plan.
All subjects evaluable for HbF change over baseline achieved increases in HbF by day 28. Changes in additional parameters, such as total bilirubin, reticulocyte count, and total hemoglobin were also observed, consistent with reduced hemolysis. A table showing the percent increase in HbF at pre-specified time-points is provided below.
| | | | | | | | | | | | | | | | | | |
Absolute HbF (%) |
| | | Baseline | | Day 14 | | Day 28 | | Day 42 | | Day 56 | | Day 70 | | Day 84 (EOS) | | Post Tx + 7D | | Increase from
baseline |
Subject 1 | | 9.2% | | 9.8% | | 10.9% | | 13.5% | | 14.0% | | 13.7% | | 13.7% | | 14.4% | | 5.2% |
Subject 2 | | 3.7% | | 5.0% | | 7.8% | | 9.6% | | 10.0% | | | | | | | | 6.3% |
Subject 3 | | 6.2% | | 6.5% | | 7.3% | | 8.3% | | | | | | | | | | 2.1% |
FTX-6058 was generally well-tolerated in the initial cohort. No serious treatment emergent adverse effects, or TEAEs, were reported, and there were no discontinuations due to TEAEs. All non-serious TEAEs were transient and deemed unrelated to study drug.
By the end of this year, Fulcrum plans to complete enrollment in the current dose cohort, as well as its second and third cohorts in this dose-ranging study, with the goal to initiate a registrational trial in 2023.
Forward-Looking Statements
This disclosure contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release are forward-looking statements, including statements regarding the potential benefits of FTX-6058 and achieving a 5-10% increase in HbF and effects on SCD, the clinical development plan for FTX-6058 and initiation of registrational trial for sickle cell disease, among others. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrum’s ability to continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod, FTX-6058 and its other product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Fulcrum’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties, and other important factors, in Fulcrum’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Fulcrum’s views as of the date hereof and should not be relied upon as representing Fulcrum’s views as of any date subsequent to the date hereof. Fulcrum anticipates that subsequent events and developments will cause its views to change. However, while Fulcrum may elect to update these forward-looking statements at some point in the future, Fulcrum specifically disclaims any obligation to do so.
