Multiple sclerosis oral new drug: Bujian tecfidera upgrade product vumerity gastrointestinal tolerance significantly improved!

November 26, 2019 / BIOON / -- Biogen recently released detailed data of phase III evolve-ms-2 study of vumerity (diroxime fumarate, biib098) Vumerity is a new oral drug approved by FDA in late October to treat recurrent multiple sclerosis (RMS) The data shows that compared with tecfidera (dimethyl fumarate, DMF, dimethyl fumarate), vumerity has improved the tolerance of gastrointestinal tract (GI) evaluated by patients Evolve-ms-2 is a multicenter, double-blind, positive drug-controlled, 5-week phase III study conducted in 506 patients with relapsing remitting multiple sclerosis (RRMS) to assess the tolerance of vumerity to tecfidera, including duration and severity The primary end point of the study was to assess the number of days reported by patients with GI symptoms with a symptom intensity score of ≥ 2 on the individual gastrointestinal symptoms and effects scale (igisis) The secondary end point was to assess the number of days for which patients reported igisis intensity score ≥ 1 or ≥ 3 GI symptoms (relative to exposure) in the entire study population, only the number of days for which igisis intensity score ≥ 2 GI symptoms in part B patients, and the total gastrointestinal symptoms and effects scale (ggisis) intensity score ≥ 1, ≥ 2 or ≥ 3 in the entire study population GI symptom days were scored according to the worst (i.e the highest) individual symptom of Isis in the study week Patients who completed the 5-week treatment period were eligible for evolve-ms-1, a 96 week open label safety study for vumerity It is worth mentioning that evolve-ms-2 is the first study to directly compare GI tolerance of two RMS treatment drugs The results showed that vumerity was significantly associated with a shorter duration, severity, and daily impact of the five major GI symptoms compared to tecfidera The primary end point results showed a 46% reduction in the number of days of self-reported igisis intensity score ≥ 2 (adjusted odds ratio [95% CI]: 0.54 [0.39-0.75], P = 0.0003) in vumerity treated patients compared to tecfidera Igisis is a new exploratory scale for patients to self evaluate the intensity and duration of major gastrointestinal symptoms, including nausea, vomiting, upper and lower abdominal pain and diarrhea In this study, the results observed by tecfidera were consistent with the known safety of the drug In addition, the results also showed that compared with tecfidera, patients treated with vumerity had a lower (1) discontinuation rate due to GI adverse events (AE) (0.8% vs 4.8%); (2) the number of days with igisis intensity score ≥ 1 and ≥ 3 was less (relative decrease 29%, relative decrease 44%); (3) the number of days with self-reported intensity score ≥ 1 (decrease 30%) was less in the global gastrointestinal symptoms and effects scale (ggisis), which assessed the overall intensity of gastrointestinal symptoms, the impact on daily activities and their degree of annoyance The days with ggisis intensity score ≥ 2 and ≥ 3 were also less (4) During the five week treatment period, the worst Isis intensity score gradually decreased The above results using the patient assessment symptom intensity scale were supported by a lower incidence of GI AE reported by study investigators (vumerity 34.8%, tecfidera 49.0%) The total incidence of AE was 78.3% in vumerity group and 83.7% in tecfidera group The severity of most AES was mild or moderate The proportion of patients who stopped the study due to AE was 1.6% in vumerity group and 5.6% in tecfidera group Alfred sandrock, executive vice president and chief medical officer of Bojian R & D, said: "we know that each patient's journey in multiple sclerosis may be very different, so Bojian's goal is to achieve individual treatment goals through our extensive combination of multiple sclerosis Tecfidera is a clinically significant treatment for patients, and we believe that vumerity is now based on our franchise, which is another compelling option for recurrent Ms " At the end of October this year, vumerity was approved by the FDA of the United States It is a new oral fumaric acid drug with a unique chemical structure, which is used for the treatment of multiple sclerosis (RMS), including clinical isolated syndrome, relapse relief disease and active secondary progressive disease Vumerity was developed by Alkermes, and Bojian has an exclusive global license for commercialization of Vumerity, which has been marketed in the United States According to the terms of the license and cooperation agreement between Bojian and Alkermes, the FDA approval will trigger Bojian to pay Alkermes a $150 million milestone payment Vumerity is an immunosuppressant It is a premedical fumaric acid monomethyl ester (MMF) with controlled-release dosage form It can be rapidly converted into MMF in vivo MMF has immunomodulatory and neuroprotective effects The neuronal degeneration of multiple sclerosis (MS) is related to oxidative stress MMF has antioxidant properties, which may help to protect myelin sheath and insulating nerve fibers Specifically, MMF can activate Nrf2 pathway, participate in cell response to oxidative stress, and may protect neurons from damage The immunoregulation of MMF may be related to the inhibition of NF KB mediated pathway, and NF KB plays a key role in the immune system Vumerity is a new oral therapy for RMS It is an upgraded version of the listed drug tecfidera (dimethyl fumarate, DMF, dimethyl fumarate), which has improved gastrointestinal tolerance It has been proved to have good efficacy, safety and tolerance in clinical research Vumerity has differential gastrointestinal (GI) tolerance due to the difference of chemical structure between vumerity and tecfidera Tecfidera can be converted into MMF to play its role in vivo The recommended starting dose of the drug is 120mg every time, twice a day, lasting for 7 days After that, the maintenance dose is 240mg every day, twice a day, with meals or on an empty stomach FDA's approval of vumerity is based on a new drug application (NDA) submitted by 505 (b) (2) regulatory approach The NDA includes pharmacokinetic bridging data comparing vumerity and tecfidera to establish bioequivalence, and is based in part on FDA's safety and efficacy results for tecfidera The mid-term exposure and safety findings of evolve-ms-1, a key phase III clinical study, were also included in the drug NDA This is a single arm, open label, 2-year safety study that is assessing the long-term safety of vumerity in patients with relapsing remitting multiple sclerosis (RRMS) The interim results of the study at the time of NDA submission included a low overall incidence (6.3%) of vumerity treatment interruptions due to adverse events, and less than 1% of vumerity treatment interruptions due to gastrointestinal (GI) adverse events Other exploratory efficacy endpoints of the study showed changes in clinical and radiologic indicators compared to baseline Key components of the vumerity clinical development project include evolve-ms-1 study, pharmacokinetic bridging study comparing vumerity with tecfidera, evolve-ms-2 study Tecfidera is a heavy MS drug of Bojian It is the largest oral MS drug in the world, and the only targeted and highly effective MS drug with more than 10 years of clinical experience In 2017, tecfidera's sales (US $4.214 billion) surpassed the peptide drug Copaxone (galatirine acetate) of TIWA / Takeda for the first time, becoming the best-selling MS drug in the world According to the 2018 performance report released by Baijian at the end of January this year, tecfidera's sales in 2018 was $4274 million In MS field, Bojian is the absolute hegemon In addition to tecbidera, Avonex (interferon β - 1A) and Tysabri (natalizumab), two other drugs of the company, also achieved global sales of US $1915 million and US $1864 million in 2018 Original source: Biogen presentations data demonstrating improved gastroenteric tolerance with vumerity Gamma (diroximel fumarate) Compared to TECFIDERA® (dimethyl fumarate)