FDA approves Ripretinib for treatment of advanced gastrointestinal mesotypes! Reding Pharma Holds China Interests

On May 15, Deciphera Pharmaceuticals announced that the FDA had approved the listing of its Qinlock (ripretinib) for the treatment of patients with advanced gastrointestinal interthelemic sylloma (GIST) who had previously been treated with Imartinib, Schonitinib and RigofiniRipretnib's listing application is based on the FDA-affiliated Centre of Excellence in Oncology (OCE) Real-Time Oncology Review Pilot Project (RTOR)This pilot project aims to explore more effective review procedures to ensure that safe and effective treatment is provided to patients as early as possible while maintaining and improving the quality of the reviewGastrointestinal mesoplasmic tumor is a tumor that affects the digestive tract and its peripheral structure in the abdomen, mostly in the stomach and small intestinegastrointestinal mesothelioma is the most common sarcoma in the gastrointestinal tract, with about 4,000 to 6,000 new cases in the United States each year, with similar incidence rates in Europe and other countries to the United States"China has about 30,000 new diagnoses each year and an estimated 100,000 patients who are already being treated for gastrointestinal mesosetan"DrLin Lin, Vice President of Peking University Oncology Hospital, Chairman of the Expert Committee of the Chinese Society of Clinical Oncology and Vice President of The Oncology Hospital of Peking Universitymost gastrointestinal mesotheliomas are driven by a series of mutations, of which the most common primary mutations are KIT kinase mutations, accounting for about 75%-80% of cases, or PDGFR alpha kinases, accounting for about 5%-10% of casesCurrent treatments cannot inhibit the primary and secondary mutations that cause drug resistance and disease progressionThe five-year survival rate for the disease is about 48%-90%, depending on the stage at the time of diagnosisthe clinical treatment practice of THE Western treatment of GIST in China is consistent, NCCN and the China Gastroenteric Intertheorsa Diagnosis and Treatment Consensus (2017 Edition) have recommended Imatinib, Schonitini, and Regfini as the first, second and third-line treatments of GIST, respectivelyWestern registered clinical studies observed that imartini had a 1-year survival rate of 88%, a median progression-free rebirth (PFS) of 24.1 weeks, and a 21-week RigfiniThe median PFS in Chinese patients, Imatinib for 20 months, Schonitinib for 35 weeks, because of the late approval of Regfini in China, only 11 registered study group of Chinese patients, domestic use has not yet been widespreadAt present, there are no approved four-line treatment drugs at home and abroadRipretinib (DCC-2618) is a new oral KIT and PDGFRA kinase inhibitor developed by Deciphera corporation in the United States Ripretinib can effectively inhibit a wide range of different mutation forms of KIT and PDGFRA kinase, including secondary drug-resistant mutations and refractory primary mutations By optimizing the binding of inhibitors with the KIT and PDGFRA regions, Ripretinib controls the activation of the switch-mediated kinase active conformation, making these carcinogenic kinases into inactive conformations In preclinical studies, the instantaneous expression results of CHO cells carrying mutations in different KIT and PDFGRA genes showed that Ripretinib had the strongest inhibition of KIT and PDGFRA primary mutations and KIT drug-resistant mutations compared to other similar products Phase 3 clinical study of INVICTUS is a randomized, double-blind, and placebo-controlled international multicenter study designed to assess the safety, tolerance, and efficacy of ripretinib in patients with advanced GIST Figure 1 INVICTUS Research Design the study included 129 patients who had received at least one treatment, including imatinib, regorafenib and sunitinib, who were randomly assigned and given ripretinib and placebo treatment on a 2:1 scale The independent central imaging committee conducted a efficacy assessment based on the mRECIST v1.1 standard program, and determined that the primary study endpoint was no progression (PFS), and the secondary study endpoint was objective mitigation rate (ORR), total survival (OS) and adverse events in treatment compared to placebo, it was found that PFS in the Ripretinib group reached 6.3 months, the placebo group was only 1.0 months (P0.0001), Ripretinib group had OS for 15.1 months, the placebo group was only 6.6 months (P 0.0005
), Ripretinib group of ORR0.00000
00000000000000000000000000000000) Ripretinib compared placebo to reduce the risk of disease progression or death by 85% Figure 3 Ripretinib compared placebo to observe lasting efficacy although there were no significant statistical differences in ORR, Ripretinib reached the main study endpoint PFS and critical secondary study endpoint OS, and significantly reduced the risk of disease progression or death by 85%, with significant clinical improvement Figure 4 Ripretinib compared placebo to reduce the risk of disease death by 64% in addition, further analysis of patients who were cross-received with Ripretinib and not withripretinib in the comfort group found that cross-treatment had significant OS benefits, with median OS in both groups being 11.6 months and 1.8 months, respectively Figure 5 The placebo group cross-received Ripretinib treatment, which can bring about OS benefits
safety analysis showed that the incidence of level 3 or 4 adverse events (TEAE) during treatment in the Ripretinib group was 5% for anemia (9%), abdominal pain (7%) and hypertension (7%) The incidence of level 3 or 4 TEAE in the placebo group was anemia (14%) In patients with reduced treatment due to TEAE, 7.1% and 2.3% were treated, respectively, and patients with discontinued treatment were 23.5% and 20.9%, respectively Phase III INVICTUS study confirmed that Ripretinib was compared to placebo for late GIST four-line or above therapy, with both PFS and OS benefits, and Ripretinib showed good tolerance experts commented that GIST is driven by KIT and PDGFRA gene mutations For patients with advanced GIST, the clinical practice of Chinese and Western treatment is consistent, NCCN and the China Gastroenteric Intertheorsa Diagnosis and Treatment Consensus (2017 Edition) have recommended Imatinib, Schonitini, and Regfini as first-, second-and-third-line treatments for GIST, respectively However, when patients receive these treatments, there is an inevitable development of drug resistance, mainly due to the follow-up of some drug-resistant mutations Currently, no standard treatment is available for patients with drug resistance after third-line treatment Patients are clinically encouraged to participate in clinical trials, and some case reports suggest that some drugs may have some effect All in all, for patients with third-line treatment of drug-resistant GIST, the need for treatment is far from being met, and a large number of patients are in urgent need of new treatments Against this background, an INVICTUS study was conducted to assess the effectiveness of the new drug Ripretinib for late GIST four-line or above treatment Unlike other kinase inhibitors, Ripretinib has a unique mechanism of action, preventing kinase from opening the switch by binding to two sites of the kinase, essentially fixing the kinase so that it cannot be activated Based on this unique mechanism of action, Ripretinib can still function in the event of drug resistance mutations in other drugs inVICTUS results further confirm the remarkable effects of Ripretinib's unique mechanism of action First, at the main endpoint, Ripretinib significantly improved PFS compared to placebo, with a median PFS of 6.3 months and 1.0 months, respectively, reducing the risk of disease progression or death by 85%, which was very encouraging Second, the Ripretinib group achieved 9.4% ORR, which is higher in value than other TKI for late GIST second- or third-line treatment This also encourages subsequent head-to-head comparisons Third, the OS in the Ripretinib group was also significantly extended, with the median OS at 15.1 months and 6.6 months, respectively, which had significant clinical significance Of particular note is that this is the first study in GIST that actually observes OS improvement THE INVICTUS FINDINGS GIVE US SOME INSIGHT SON, THAT EVEN IN THE LATER STAGES OF THE DISEASE SHOULD BE ACTIVELY TREATED, AND THAT THERE IS A VERY LARGE CLINICAL BENEFIT TO THE POTENTIAL FOR RAPID PROGRESS IN PATIENTS WHO DO NOT RECEIVE ACTIVE TREATMENT AFTER MULTI-LINE TREATMENT Finally, the safety analysis shows that Ripretinib is safe, well tolerated, and the side effects are mostly minor Overall, based on this finding, Ripretinib is expected to become the new standard treatment for patients with advanced GIST after multi-line treatment In addition, research on the use of Ripretinib than schoinatinib for late GIST second-line therapy is also being carried out, and the results are worth looking forward to In June 2019, Reed Ingle Pharmaceuticals and Deciphera reached an exclusive licensing agreement to acquire The Development and Commercialization of Ripretinib in Greater China (China, Hong Kong, Macau and Taiwan) Under the terms of the agreement, Deciphera will receive a $20 million cash advance and be eligible for potential development and business milestone payments of up to $185 million In addition, Retin Pharma will pay Royalties to Deciphera based on Ripretinib's annual net sales in Greater China on Ripretinib Ripretinib, a clinically developed experimental KIT/PDGFR alpha kinase switching regulatory inhibitor for the treatment of KIT/PDGFR alpha-driven gastrointestinal interthelisal tumor (GIST), systemic hyperblastoma (SM), and other cancers Ripretinib is specifically designed to improve treatment in patients with gastrointestinal mesomal tumors by inhibiting broad-spectrum mutations in KIT and PDGFR alpha Ripretinib blocks the initial and secondary KIT mutations in the 9, 11, 13, 14, 17 and 18 exons involved in gastrointestinal mesoplasmic tumors, as well as the primary 17 exon D816V mutations found in SM Ripretinib also inhibits primary PDGFR alpha mutations in the 12th, 14th and 18th exons, including gastrointestinal mesoplasmic tumors involving the 18th exon D842V mutation on Reeding Pharmaceuticals Andding Pharmaceuticals (NASDAQ: ZLAB) is an innovative biopharmaceutical company based in China and operates worldwide, dedicated to providing patients in China and around the world with innovative drugs in the field of cancer, autoimmune and infectious diseases The company's experienced team has partnered with the world's leading biopharmaceutical companies to create a range of innovative drugs to meet the rapid growth of the Chinese pharmaceutical market and unmet medical needs worldwide The vision of Retin Pharmaceuticals is to become a comprehensive and innovative biopharmaceutical company, developing, producing and selling products developed and developed and partnered in china, in order to promote the health and well-being of human beings around the world author: MedSci Source: MedSci Original