The Italfarmaco group announces the first positive data from the phase 3 trial showing the beneficial effect of givinostat in patients with Duchenne muscular dystrophy

— Study Meets Primary Endpoint, Secondary and Exploratory Endpoints Showing Consistency with Primary Endpoint —

— The data reinforce the safety profile previously observed for Givinostat; treatment in boys with DMD continues to show good safety profile —

— The Company Plans to Discuss the Possibility of Submitting a Marketing Application to Regulatory Authorities for Givinostat in DMD —

— The results were presented at the PPMD ​​annual conference on June 25, 2022 —

MILAN, June 26, 2022–(BUSINESS WIRE)–Italfarmaco Group today announced positive early data from its completed Phase 3 EPIDYS trial with Givinostat, the company’s proprietary histone deacetylase (HDAC) inhibitor, in boys with Duchenne muscular dystrophy (DMD). The primary objective of the study was to assess the effects of Givinostat on slowing disease progression in ambulatory DMD boys aged 6 years and older on chronic steroids. The study compared Givinostat to placebo and achieved the primary endpoint (change from baseline in time to climb 4 steps) after 18 months of treatment in the target population1 with key secondary endpoints consistent with the functional primary endpoint. Givinostat continued to demonstrate a safety profile consistent with previous studies. The main data was presented by the Chief Medical Officer of the Italfarmaco Group, Dr. Paolo Bettica, on June 25, 2022, during the hybrid Parent Project on Muscular Dystrophy (PPMD) Annual Conference.

In October 2020, the United States Food and Drug Administration (FDA) granted Givinostat Rare Pediatric Disease Designation for the treatment of DMD. Previously, the company also received orphan drug designation from the FDA and EMA, and Fast Track designation from the FDA. Based on the study results, which show that adding Givinostat to steroid therapy results in clinical benefits for study participants, the Company plans to meet with U.S. and European regulators to discuss the opportunity to submit a marketing application and solicit comments on a future submission of regulatory approval application. The company intends to submit the full results of the EPIDYS study for publication in a peer-reviewed journal in due course.

“These early Phase 3 results in DMD add to the growing dataset we have collected over the past several years that have shown positive results with our investigational therapeutic candidate, Givinostat, when taken with steroids in patients with DMD, offering new hope to boys with DMD. , their families and the medical community,” said Paolo Bettica, MD, PhD, Italfarmaco Group Chief Medical Officer. “There is a huge unmet medical need for additional drugs to treat this debilitating rare disease and with these positive results, we intend to meet with regulatory agencies to share these findings and discuss a way forward to submit the ‘full dataset in a marketing application for a potential We are extremely excited to share these positive new insights from the EPIDYS trial with the community and would like to thank all stakeholders involved.’

The EPIDYS Phase 3 clinical trial is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Givinostat in people with DMD (Cinicaltrials.gov: NCT02851797). The trial recruited 179 ambulant males with an average age of 9 and on stable steroids for at least 6 months. The boys were randomized 2:1 and chronically treated with Givinostat oral suspension or placebo for an 18-month period. Among them, 120 boys formed the target population1.

Overview of clinical results
Main criterion: The mean change from baseline to climbing 4 steps was selected as the primary endpoint to assess the efficacy of Givinostat compared to placebo. The results demonstrated a slower decline in the performance of this functional task in the group treated with Givinostat (difference vs. placebo of 1.78 seconds, p=0.0345).

Key Secondary Endpoints: Various secondary endpoints were analyzed and showed results consistent with the primary functional endpoint. These included functional tests such as the North Star Ambulatory Assessment (NSAA) and the Time to Rise Test (TTR) as well as muscle strength analyses. Fat infiltration into the vastus lateralis (VL) muscle of the thigh is a hallmark of disease progression in patients with DMD and has been measured using a noninvasive objective imaging method called magnetic resonance spectroscopy (MRS) to assess the effectiveness of Givinostat. The data indicated that treatment with Givinostat delayed fat infiltration by approximately 30% (difference vs placebo, -2.9%, nominal p=0.035). Additional exploratory endpoints were also analyzed in the clinical study. These results further confirm the potential of Givinostat as a clinical benefit for boys with DMD.

Security and tolerance: The majority of adverse events (AEs) were mild to moderate in intensity (95%). Three boys (2.5%) treated with Givinostat withdrew from the trial due to an AE. Similar to previously observed adverse reactions occurring in at least 1 in 10 subjects were diarrhea, abdominal pain, thrombocytopenia, hypertriglyceridemia, decrease in platelets and increase in triglycerides. Givinostat tolerance was managed with appropriate monitoring and dose adjustments. No other security issues were observed.

Professor Eugenio Mercuri, Professor of Pediatric Neurology at the Catholic University of Rome, Italy, commented: “These results show the beneficial effect of Givinostat in boys with DMD, proving its ability to slow disease progression.”

“I believe the results of the EPIDYS study are clinically meaningful, are consistent with previous findings, and further demonstrate that givinostat can slow muscle deterioration, leading to a reduction in muscle function decline,” added Teacher. Craig McDonald, professor in the Department of Pediatrics and Physical Medicine and Rehabilitation at the University of California, Davis.

About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a serious genetic neuromuscular disease characterized by progressive muscle weakness and degeneration and is the most common type of muscular dystrophy in the world. DMD is caused by mutations in the DMD gene that result in the absence of a functional dystrophin protein, which plays a crucial role in maintaining the structural and membrane stability of muscle fibers. The disease primarily affects boys with symptoms usually seen between the ages of two and five that worsen over time with individuals losing their ability to walk. Eventually, the heart and respiratory muscles are affected, leading to premature death. The incidence of DMD is approximately 1 in 3500 to 6000 male births worldwide.

About Givinostat
Givinostat is an investigational drug discovered through internal research and development efforts of Italfarmaco Group in collaboration with Lorenzo Puri (Sanford Burnham Prebys Medical Research Institute, San Diego, formerly Santa Lucia Foundation, Rome) and his team, and partnerships with Telethon and Parent Project aps. Its safety and efficacy are being evaluated for the treatment of Duchenne and Becker muscular dystrophy. Givinostat inhibits histone deacetylases (HDACs). HDACs are enzymes that prevent gene translation by altering the three-dimensional folding of DNA in the cell. Studies show that higher than normal HDAC activity in people with DMD can prevent muscle regeneration and also trigger inflammation. In the company’s DMD clinical study, in boys aged 7 to less than 11 years, Givinostat was observed to slow the progression of the disease, significantly increase muscle mass and reduce the amount of fibrotic tissue . In this study, treatment with Givinostat also significantly reduced muscle tissue necrosis and fat replacement, two additional endpoints related to disease progression (Bettica et al., Neuromuscular Disorders 2016).

About Italfarmaco Group
Italfarmaco Group is a specialty pharmaceutical company engaged in the discovery, development, manufacture and marketing of branded prescription and over-the-counter products in more than 60 countries on 5 continents. Italfarmaco Group’s research and development expertise is best demonstrated by its HDAC inhibitor development programs, addressing new therapeutic treatments for specialized and rare diseases. Through both marketed drugs and compounds in development, Italfarmaco Group is dedicated to serving patients whose needs remain largely unmet.

1 Target population: Individuals with a Vast External Muscle Fat Fraction (VL MFF) assessed by Magnetic Resonance Spectroscopy (MRS) in the range >5% and ≤30%

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