Motor Disorders

SILVER SPRING, Md., March 18, 2024 /PRNewswire/ -- Today, the U.S. Food and Drug Administration approved Lenmeldy (atidarsagene autotemcel), the first FDA-approved gene therapy indicated for the treatment of children with pre-symptomatic late infantile, pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD). Metachromatic leukodystrophy is a debilitating, rare genetic disease affecting the brain and nervous system. It is caused by a deficiency of an enzyme called arylsulfatase A (ARSA), leading to a buildup of sulfatides (fatty substances) in the cells. This buildup causes damage to the central and peripheral nervous system, manifesting with loss of motor and cognitive function and early death. It is estimated that MLD affects one in every 40,000 individuals in the United States. There is no cure for MLD, and treatment typically focuses on supportive care and symptom management. "This is the first FDA-approved treatment option for children who have this rare genetic disease," said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER). "We remain committed to advancing scientific and regulatory principles that enable the efficient development and review of safe, effective and innovative products that have the potential to change patients' lives." Lenmeldy is a one-time, individualized single-dose infusion made from the patient's own hematopoietic (blood) stem cells (HSCs), which have been genetically modified to include functional copies of the ARSA gene. The stem cells are collected from the patient and modified by adding a functional copy of the ARSA gene. The modified stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow. The modified stem cells supply the body with myeloid (immune) cells that produce the ARSA enzyme, which helps break down the harmful build-up of sulfatides and may stop the progression of MLD. Prior to treatment, patients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in Lenmeldy. "MLD is a devastating disease that profoundly affects the quality of life of patients and their families. Advancements in treatment options offer hope for improved outcomes and the potential to positively influence the trajectory of disease progression," said Nicole Verdun, M.D., director of the Office of Therapeutic Products in CBER. "This approval represents important progress in the advancement and availability of effective treatments, including gene therapies, for rare diseases." The safety and effectiveness of Lenmeldy was assessed based on data from 37 children who received Lenmeldy in two single-arm, open-label clinical trials and in an expanded access program. Children who received treatment with Lenmeldy were compared to untreated children (natural history). The primary efficacy endpoint was severe motor impairment-free survival, defined as the interval from birth to the first occurrence of loss of locomotion and loss of sitting without support or death. In children with MLD, treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared with untreated children. All children with pre-symptomatic late infantile MLD who were treated with Lenmeldy were alive at 6 years of age, compared to only 58% of children in the natural history group. At 5 years of age, 71% of treated children were able to walk without assistance. Eighty five percent of the children treated had normal language and performance IQ scores, which has not been reported in untreated children. In addition, children with pre-symptomatic early juvenile and early symptomatic early juvenile MLD showed slowing of motor and/or cognitive disease. The most common side effects of Lenmeldy are fever and low white blood cell count, mouth sores, respiratory infections, rash, medical line infections, viral infections, fever, gastrointestinal infections and enlarged liver. After infusion with Lenmeldy, patients should be monitored for neutrophil counts and risk of delayed platelet engraftment until engraftment has been achieved. Treatment with Lenmeldy may be associated with formation of blood clots or a type of swelling of brain tissues known as encephalitis. There is a potential risk of blood cancer associated with this treatment; however, no cases have been seen in patients treated with Lenmeldy. Patients receiving this product should have lifelong monitoring for hematologic malignancies, including a complete blood count (with differential) annually and integration site analysis, as warranted, for at least 15 years after treatment. The application received Priority Review, Orphan Drug, Rare Pediatric Disease and Regenerative Medicine Advanced Therapy (RMAT) designations. The FDA granted approval of Lenmeldy to Orchard Therapeutics. Media Contact: Carly (Kempler) Pflaum, [email protected], 240-672-8872 The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, radiation-emitting electronic products, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration

Data published in The Lancet Neurology showed favorable efficacy of ND0612 compared to oral immediate-release levodopa/carbidopa REHOVOT, Israel, March 18, 2024 /PRNewswire/ -- NeuroDerm Ltd., a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), today announced the publication of results in The Lancet Neurology from the pivotal, Phase 3 BouNDless trial (NCT04006210). Results from the trial, which evaluated the efficacy, safety and tolerability of investigational ND0612 – a continuous, 24 hours/day subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) – in comparison to oral immediate-release (IR) LD/CD in Parkinson's disease (PD) patients with motor fluctuations, met its primary endpoint and the first four secondary endpoints, and showed ND0612 was superior at increasing "ON" time without troublesome dyskinesia and reducing "OFF" time, compared to oral IR-LD/CD after 12 weeks. "Orally administered levodopa/carbidopa tablets remain the most essential pharmacological intervention in Parkinson's disease; however, over time, the reliability of its benefits can decrease, leading to the onset of motor fluctuations", said Professor Alberto Espay, Principal U.S. Investigator of the BouNDless trial and Director of the James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders at the University of Cincinnati. "We are encouraged by these positive data, which we believe support ND0612, if approved, as a potential treatment option for people with Parkinson's disease experiencing motor fluctuations who have thus far had limited options." Study participants entered an open label IR-LD/CD optimization phase followed by an open label ND0612 plus IR-LD/CD optimization phase and were then randomized to a 12-week double-blind double-dummy (DBDD) treatment period with either ND0612 or oral IR-LD/CD regimens. Key study findings include: Treatment with ND0612 demonstrated superior efficacy with a statistically significant addition (p<0.0001) of 1.72 hours in "ON" time without troublesome dyskinesia over oral IR-LD/CD, thus meeting the trial's primary endpoint. The trial also demonstrated statistically significant and clinically meaningful results for the first four secondary endpoints, including the key secondary endpoint with an additional 1.4-hour reduction in daily "OFF" time (p<0.0001) with ND0612 vs. oral IR-LD/CD. Additional secondary endpoints that reached statistical significance and clinically relevant improvement for both patients and their physicians were the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II scores (-3.05 [-4.28, -1.81], p<0.0001), the Patients Global Impression of Change (Odds Ratio [OR]: 5.31 [2.67, 10.58], p<0.0001) and Clinician Global Impression of Improvement (OR: 7.23 [3.57, 14.64], p<0.0001). The systemic safety profile of ND0612 was consistent with the well-established safety profile of oral standard of care LD/CD. As expected, due to its mode of continuous subcutaneous administration, infusion site reactions (ISRs) were the most frequent reported treatment emergent adverse events (57% for ND0612 vs. 43% for IR-LD/CD during the DBDD period of the study). Most ISRs were of mild severity. Of note, dyskinesia, falls and ON/OFF phenomena were reported less frequently in the ND0612 group compared to the IR-LD/CD group. Additionally, only 6% of study participants in the ND0612 group discontinued the trial during the DBDD period due to any reason, compared to 6% in the oral IR-LD/CD group. "Motor fluctuations are an all-too-common symptom associated with the use of oral LD/CD in Parkinson's disease, often causing significant disruptions to day-to-day life as the disease progresses," said Tami Yardeni, EVP, Clinical Development, NeuroDerm. "We now have compelling evidence to support the favorable benefit-risk profile of ND0612. These results show significant improvement of motor fluctuations, as well as improvements in the experiences of daily living for this challenging patient population." Analyses of results from the ongoing BouNDless trial complement the long-term safety data from the BeyoND study (NCT02726386) including patients in their eighth year of follow-up.1 About Parkinson's Disease Parkinson's disease affects more than 10 million people worldwide. It is caused by decreasing dopamine signaling in the brain as dopaminergic brain cells die off. Levodopa is the most important replacement therapy for Parkinson's disease, administered together with a levodopa degradation inhibitor (usually carbidopa). Oral levodopa intake leads to fluctuating plasma concentrations, with high peaks and low troughs that contribute to the progressive emergence of disabling clinical oscillations over the day in the motor function of many people with Parkinson's disease. With disease progression, adjustments in oral levodopa therapy become less and less effective in managing such motor complications, leaving patients with limited treatment options that are highly invasive. About ND0612 ND0612 is an investigational drug-device combination therapy – a 24-hours/day, continuous subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) for the treatment of motor fluctuations in people with Parkinson's disease (PD). The safety and efficacy of ND0612 in PD is under review by the U.S. Food and Drug Administration (FDA) who has assigned a Prescription Drug User Fee Act (PDUFA) target action date for the second quarter of CY (calendar year) 2024. About NeuroDerm, Ltd. NeuroDerm, Ltd. is a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), based in Israel, inspired to reduce disease burden and improve the quality of life of patients and their families through innovative drug-device combination therapies and technologies. NeuroDerm is a pharmaceutical and medical technology integrated company developing central nervous system (CNS) product candidates that are designed to address major deficiencies of current treatments. For additional information, please visit NeuroDerm's website at  or follow us on LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678, and focusing on ethical pharmaceuticals. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction by identifying patient populations with high potential for efficacy and safety. In addition, MTPC is working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly owned subsidiary of Mitsubishi Tanabe Pharma Corporation's (MTPC) 100% owned U.S. holding company, Mitsubishi Tanabe Pharma Holdings America, Inc. It was established by MTPC to commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on Twitter, Facebook and LinkedIn. __________________________________ 1S Isaacson, et al. Long-term safety of continuous levodopa/carbidopa infusion with ND0612: Results from the ongoing BeyoND study. Poster presented at: American Academy of Neurology Annual Meeting; 2022 Apr 2-7; Seattle, WA. Logo -

Pivotal Phase 3 data, published in The Lancet Neurology, showed favorable efficacy of ND0612 compared to oral immediate-release levodopa/carbidopa JERSEY CITY, N.J., March 18, 2024 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced the publication of results in The Lancet Neurology from the pivotal, Phase 3 BouNDless trial (NCT04006210) evaluating the efficacy, safety and tolerability of investigational ND0612 – a continuous, 24 hours/day subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) – in comparison to oral immediate-release (IR) LD/CD in people with Parkinson's disease (PD) experiencing motor fluctuations. Results from the study, which met its primary endpoint and the first four secondary endpoints, showed ND0612 was superior at increasing "ON" time without troublesome dyskinesia and reducing "OFF" time, compared to oral IR-LD/CD after 12 weeks. "Orally administered levodopa/carbidopa tablets remain the most essential pharmacological intervention in Parkinson's disease; however, over time, the reliability of its benefits can decrease, leading to the onset of motor fluctuations," said Professor Alberto Espay, Principal U.S. Investigator of the BouNDless trial and Director of the James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders at the University of Cincinnati. "We are encouraged by these positive data, which we believe support ND0612, if approved, as a potential treatment option for people with Parkinson's disease experiencing motor fluctuations who have thus far had limited options." Study participants entered an open label IR-LD/CD optimization phase followed by an open label ND0612 plus IR-LD/CD optimization phase and were then randomized to a 12-week double-blind double-dummy (DBDD) treatment period with either ND0612 or oral IR-LD/CD regimens. Key study findings include: Treatment with ND0612 demonstrated favorable efficacy with a statistically significant addition (p<0.0001) of 1.72 hours in "ON" time without troublesome dyskinesia over oral IR-LD/CD, thus meeting the trial's primary endpoint. The trial also demonstrated positive and clinically meaningful results for the first four secondary endpoints, including the key secondary endpoint with an additional 1.4-hour reduction in daily "OFF" time (p<0.0001) with ND0612 vs. oral IR-LD/CD. The remaining secondary endpoints that reached statistical significance were the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II scores (-3.05 [-4.28, -1.81], p<0.0001), the Patients Global Impression of Change (Odds Ratio [OR]: 5.31 [2.67, 10.58], p<0.0001) and Clinician Global Impression of Improvement (OR: 7.23 [3.57, 14.64], p<0.0001). The systemic safety profile of ND0612 was consistent with the well-established safety profile of oral standard of care LD/CD. Infusion site reactions (ISRs) were the most reported treatment emergent adverse events (TEAEs) in any group during the DBDD period (57% for ND0612 vs. 43% for IR-LD/CD). Some ISRs (infusion site nodule, infusion site bruising, infusion site infection, infusion site erythema, infusion site pain, infusion site eschar and infusion site swelling) were more frequent in the ND0612 group compared to placebo and oral LD/CD groups. Additionally, only 6% of study participants discontinued the trial during the DBDD period due to any reason – including 5% due to AEs – compared to discontinuation rates of 6% and 3%, respectively, of study participants in the oral LD/CD groups. "These findings from the BouNDless study show us that continuous, subcutaneous delivery of levodopa/carbidopa with ND0612 has the potential to impact people living with Parkinson's disease who experience motor fluctuations," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "We look forward to the continued evaluation of ND0612 to further our understanding of its effect in Parkinson's disease, and as a part of our commitment to address unmet needs for this patient population." Analyses of results from the ongoing BouNDless trial complement the long-term safety data from the BeyoND study (NCT02726386) assessing ND0612, with some patients in their eighth year of follow-up.1 About ND0612 ND0612 is an investigational drug-device combination therapy – a 24-hours/day, continuous subcutaneous (SC) infusion of liquid levodopa/carbidopa (LD/CD) for the treatment of motor fluctuations in people with Parkinson's disease (PD). Development of investigational ND0612 is being led by NeuroDerm, Ltd., a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). The safety and efficacy of ND0612 in PD is under review by the U.S. Food and Drug Administration (FDA), who has assigned a Prescription Drug User Fee Act (PDUFA) target action date for the second quarter of CY (calendar year) 2024. About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . About NeuroDerm, Ltd. NeuroDerm, Ltd. is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), based in Israel, inspired to reduce disease burden and improve the quality of life of patients and their families through innovative drug-device combination therapies and technologies. NeuroDerm is an integrated pharmaceutical and medical technology company developing central nervous system (CNS) product candidates. For additional information, please visit NeuroDerm's website at  or follow the Company on LinkedIn. Media inquiries: [email protected] 1 S Isaacson, et al. Long-term safety of continuous levodopa/carbidopa infusion with ND0612: Results from the ongoing BeyoND study. Poster presented at: American Academy of Neurology Annual Meeting; 2022 Apr 2-7; Seattle, WA. SOURCE Mitsubishi Tanabe Pharma America