New drugs for rare diseases! Arimoclomol, a heat shock response inducer, has a strong therapeutic effect in the treatment of Niemann peak disease type C. It has been applied for listing this year!

January 4, 2020 / BIOON / - orphozyme, a biopharmaceutical company in Denmark, focuses on the development of innovative drugs for the treatment of rare protein misfolded diseases Its platform is based on the early scientific discovery of heat shock proteins (HSPs) Recently, the company released the 12-month interim data of phase II / III clinical study of arimoclomol in the treatment of Niemann Pick disease type C (NPC) Long term data show that arimoclomol treatment has continued to have a positive impact on disease progression over the past two years In addition, the data from the post genome subgroup analysis provide more evidence for the efficacy of arimoclomol In general, these new data strengthen the regulatory applications of arimoclomol in the United States and Europe Alphazyme has planned to submit a new drug application (NDA) for arimoclomol to the US Food and Drug Administration (FDA) in the first half of 2020, and the drug is expected to be approved in the first half of 2021 In addition, the company plans to submit a marketing authorization application (MAA) to the European Drug Administration (EMA) in the second half of 2020 "We are very encouraged by the 12-month results of the open label extension study," said Thomas blaettler, chief medical officer of orphozyme During two years of treatment, arimoclomol has a sustained effect on the progression of the disease In addition, in a placebo-controlled trial, patients who were initially randomized to placebo had a 90% reduction in progression after switching to arimoclomol NPC is a devastating disease, arimoclomol is a promising compound, which has the potential to change the life of patients We look forward to submitting the application for listing as soon as possible and bringing this innovative therapy to the market to address the major unmet needs of NPC, a devastating disease " Arimoclomol is a leading compound of orphozyme company It is a small molecule heat shock stress inducer, which can amplify the production of heat shock protein (HSP) Heat shock response is a protective system which is responsible for the treatment of cell stress and is involved in the maintenance of proper protein folding HSP can save defective misfolded proteins, clear protein aggregates and improve lysosomes function After oral administration, arimoclomol can be quickly dispersed to the whole body, and can pass through the blood-brain barrier and enter the brain The drug can play a role in stress cells by stimulating the heat shock response of cells, helping the misfolded proteins to restore normal function, or using the cell recovery system lysosome to recover these proteins when they can not restore normal function, so that they will no longer form toxic accumulation, which will help to reduce the accumulation of misfolded proteins Quality may be the cause of many diseases and symptoms At present, arimoclomol is being developed as a potential therapy for four rare diseases, including two lysosomal storage diseases (Niemann Pick disease type C [NPC] and Gaucher disease [GD]) and two neuromuscular diseases (sporadic inclusion body myositis [sIBM], amyotrophic lateral sclerosis [ALS]) The drug has been studied in 7 phase I and phase II clinical trials Niemann Pick disease type C (NPC) is a hereditary, progressive, debilitating and often fatal neurovisceral disease The disease belongs to a family called lysosomal storage disease, which is caused by mutations that cause NPC protein defects As a result, lipids, usually cleared by lysosomes, accumulate in tissues and organs, including the brain, and drive disease pathology In the United States and Europe, the number of NPC patients is estimated at 1000-2000 Currently, there is no approved treatment drug for NPC in the United States, and only one drug has been approved in Europe Arimoclomol has been awarded orphan drug qualification for treatment of NPC in the United States and the European Union In the United States, arimoclomol has also been awarded rare paediatric drug qualification, fast track qualification (U.S.) and breakthrough drug qualification Arimoclomol has been proved to have a clinically significant role in the progression of NPC, which is further supported by the biomarker effect, which shows that it has an impact on the biological basis of the disease, and has good safety and tolerance Adam, NPC patient (photo source: nnpdf ORG), arimoclomol treatment of NPC phase II / III results confirm that the British drug and health care products Administration (MHRA) conducted routine examination on the clinical research institutions that conducted the trial on behalf of orphozyme In accordance with the procedure agreed with MHRA, the test data were reanalyzed and the overall efficacy and safety previously reported were confirmed On the basis of routine clinical nursing plus arimoclomol treatment, the treatment difference in the main end point (measured by 5-threshold clinical severity scale [5-threshold npccss]) was - 1.34 (the same as previously reported), P value was 0.0537 The new gene subgroup analysis further supports the robustness of phase II / III test results: in NPC, homozygous functional nonsense mutations indicate early onset and rapid progression of disease FDA recommends analyzing the effect of homozygous mutations on the results of the study In the placebo-controlled phase of the trial, all patients with homozygous functional nonsense mutations (n = 3) were under 4 years old and randomly assigned to the arimoclomol treatment group (3 out of 4 arimoclomol treatment patients in this subgroup) If the imbalance of treatment allocation was considered, the effect of arimoclomol on disease progression was statistically significant (P = 0.024) compared with placebo Continuous efficacy and continuous reduction of disease progression: the 12-month open label expansion results of phase II / III randomized placebo-controlled trial (ct-orzy-npc-002) confirmed the continuous clinical benefits of arimoclomol within 2 years of treatment, and further proved its efficacy and safety 41 patients who completed the 12-month double-blind phase of the trial continued to enter the open label extension period, and all patients received arimoclomol treatment Patients who switched from placebo to arimoclomol experienced a similar degree of reduction in disease progression in patients assigned to arimoclomol during the placebo-controlled period (using 5-domain npccss, the open label extension period was 0.23 progression vs placebo control period was 2.0 progression) Compared with the placebo-controlled group, patients who received arimoclomol for 2 years showed greater progress in the open label extension period This is mainly due to the continuous aggressive disease process in patients under 4 years old Among the pre-defined subgroups of patients ≥ 4 years old and patients receiving miglustat (meglut) as part of routine clinical care, the benefits of early initiation of arimoclomol therapy were greater than those of delayed initiation therapy, which indicated that arimoclomol therapy changed the course of disease During 24 months of treatment, arimoclomol was safe and well tolerated Source of original text: orphozyme reports positive arimoclomol data from open label phase 2 / 3 extension in Niemann Pick disease type C