Tests for Duchenne muscular dystrophy drugs typically assess how well people with muscular dystrophy perform tasks, such as walking. The key measure in the key test of Italfarmaco Group’s Duchenne drug givinostat is stair climbing. Less than two seconds doesn’t seem like much, but when it comes to oral medication, it can mean everything. These seconds represent the time difference between patients who received the experimental treatment and those who received a placebo. Italfarmaco said the results showed its drug slowed muscle decline and paved the way for discussions with regulators to seek marketing authorization.
This Phase 3 preliminary results Presented Saturday during the annual meeting of the Parent Project Muscular Dystrophy, a patient group.
Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder that causes insufficient levels of dystrophin, a key muscle protein. The disease, which mainly affects boys, begins to show its muscle-weakening effects between the ages of 2 and 5. Over time, patients lose the ability to walk. The effects of Duchenne on the heart and lungs often lead to death in patients in their 20s.
Givinostat is a small molecule designed to block histone deacetylase (HDAC). This enzyme alters the three-dimensional folding of DNA, preventing gene translation. Privately held Italfarmaco noted that studies have shown that patients with Duchenne have higher-than-normal HDAC activity, which may prevent muscle regeneration and cause inflammation. By blocking HDAC, givinostat aims to slow the progression of Duchenne.
In a phase 3 trial of the Italfarmaco drug, 179 boys aged 6 years and older were randomly assigned to receive an oral suspension or a placebo twice a day for 18 months. The participants had been chronically treated with steroids, a standard Duchenne therapy. The anti-inflammatory and immunosuppressive effects of steroids are thought to slow the progression of the disease.
The main goal of the study was to measure the time it takes to climb four flights of stairs. According to the results presented by Italfarmaco, patients who received givinostat had a slower decline in the ability to perform stair climbing tasks than patients who received a placebo. On average, the difference is 1.78 seconds. Secondary objectives of the study included measuring the time to stand up from the floor and the six-minute walk test. Compared with the placebo group, the giveinostat group experienced a 3.28-second reduction in wake-up time, Italfarmaco said. For the six-minute walk test, the company said there was a small decrease in both treatment groups over time.
The six-minute walk test is the main goal of the key test Exondys 51, the first FDA-approved Duchenne therapy. In that small study, there was no significant difference between the patients who received the drug and the control group. Exondys 51, an antisense oligonucleotide that allows the cell’s protein-making machinery to produce a shorter but still functional version of dystrophin, Accelerated approval in 2016 Surrogate endpoint of increased dystrophin production observed in some patients.The drug’s maker, Sarepta Therapeutics, continues to win Two more Duchenne drugs approvedEach of Sarepta’s three approved Duchenne therapies targets a different genetic subgroup of patients.
Italfarmaco, Sarepta and other drug developers are working on Expanding the range of Duchenne treatments Use different treatments and potentially help more patients. Sarepta, Solid Biosciences and Pfizer has both conducted clinical trials with gene therapy Delivers a gene that produces dystrophin to cells.
Sarepta’s research also includes an improved next-generation drug based on Exondys 51, whose technology helps to better penetrate tissue and increase dystrophin production. But the experimental therapy, SRP-5051, ran into setbacks.The Cambridge, Massachusetts-based biotech announced last Thursday that the FDA has placed the clinical hold In Phase 2 testing after observing low levels of magnesium in the patient’s blood. The patient was treated with magnesium supplementation and the complications resolved within three days, Chief Scientific Officer Louise Rodino-Klapac said on the conference call.The company is responding to the FDA’s request for safety information, and the study is continuing outside the U.S.
Adverse reactions observed in the givinostat test were mild to moderate and included diarrhea, abdominal pain, low blood platelet levels and increased blood triglyceride levels, Italfarmaco said. Based on the latest results of givinostat in Duchenne patients, the company plans to meet with U.S. and European authorities. Italfarmaco also plans to submit the full results of the Phase 3 study for publication in a peer-reviewed journal.
“There is a huge unmet medical need for additional medicines to treat this debilitating rare disease, and with these positive results, we intend to meet with regulators to share these findings and discuss full data submission in a marketing application potential pathway approval for the set,” Italfarmaco Chief Medical Officer Paolo Bettica said in a prepared statement. “
It’s not all smooth sailing for givinostat. Italfarmaco had previously tested the drug in another muscle disease, Becker muscular dystrophy.Last summer, the company reported Phase 2 testing of the directive Failure To achieve the primary goal of showing fibrotic or scar tissue changes, as measured from muscle biopsy. Although it failed to show a significant difference from placebo on this endpoint, Italfarmaco noted that there was a significant difference from placebo in muscle deterioration as assessed by MRI scans of the leg muscles.
Photos by Flickr users Jemetlaw through Creative Commons license
