DMD Innovative Therapy's FDA Accelerates Approval of Keytruda Single Drug Treatment NSCLC Highlights "Power"

At the 61st annual meeting of the American Society of Hematology (ASH), Sangamo Therapeutics and Pfizer jointly announced the interim results of SB-525, a gene therapy for severe haemophilia type A, in a Phase 1/2 clinical trial called AltaThe results showed that all patients treated with the highest dose of SB-525 had the normal level of blood coagulation factor VIIITwo of the patients followed up for 44 and 37 weeksThis therapy has entered phase 3 of clinically registered studiesSB-525 is a gene therapy based on recombinant AAV6 vectorsIts design has improved liver-specific promoters, genetic ally of coding factor VIII, as well as polyadenosine signals (polyA) and viral vector sequences, not only to optimize the efficiency of vector production, but also to improve the expression of liver-specific factor VIII proteinIn a Phase 1/2 clinical trial called Alta, 11 patients with severe haemophilia were divided into four groups and treated with different doses of SB-525 in a Phase 1/2 clinical trial called AltaAs of 17 October this year, five patients had been treated with gene therapy at a dose of 3e13 vg/kg (the highest dose)Testing of factor VIII showed that the factor VIII activity in these patients reached normal levels 5-7 weeks after receiving SB-525 treatmentTwo of the patients (patients 7 and 8) had stable factor VIII levels and lasted 44 and 37 weeksMoreover, all patients treated with the highest dose of SB-525 did not experience bleeding at a time of up to 44 weeks of follow-upMoreover, this group of patients did not receive factor VIII replacement therapy after initially receiving the preventive factor VIII injectionTotal survival improved significantly! The new BMS acute myeloid leukemia drug reached the end of Phase 3, Bristol-Myers Squibb (BMS) announced at the 61st annual meeting of the American Society of Hematology (ASH) that its CC-486 as a maintenance therapy, in the treatment of acute myeloid leukemia patients in the phase 3 critical trial QUAZAR AZAR-001, compared to the total survival of the patient (OS) and no relapse Based on the positive results of the QUAZAR AML-001 trial, Baxter plans to submit a new drug application (NDA) for CC-486 in the first half of 2020CC-486 is a DNA methyl metastase inhibitor (DNMT inhibitor) that alters gene expression at epigenetic levels and inhibits the proliferation of cancer cellsIn addition to being used in clinical trials for Patients with AML, CC-486 also treats Patients with T-cell lymphoma in Phase 2 clinical trials, as well as patients with myelogenic abnormality syndrome (MDS) in Phase 2 and 3 trialsCompared to placebo, CC-486 significantly improved OS in AML patients (Photo: BMS Official Website) A 3-phase trial of a randomized, double-blind, placebo-containing control groupPatients who participated in the trial had moderate/low-risk AML and had achieved the first complete remission (CR) or full remission and incomplete blood cell count relief (CRi) after receiving strong induced chemotherapy The results showed a significant improvement in OS in patients in the CC-486 treatment group at a median follow-up time of 41.2 months compared to the placebo group, with the median OS in the CC-486 group of patients at 24.7 months and the placebo group at 14.8 months, reaching the primary endpoint of the trial The median RFS was 10.2 months for patients in the treatment group, compared with 4.8 months in the placebo group In addition, the health-related quality of life (HRQoL) score of patients in the CC-486 group was maintained at the baseline during treatment, reaching the critical secondary endpoint of the trial The disease control rate of refracted breast cancer is 97.3%! Heavy ADC therapy reached the clinical primary endpoint AstraZeneca and Daiichi Sankyo jointly announced that the joint lying antibody coupling drug (ADC) (fam-) trastuzumab deruxtecan (DS-8201) reached the primary end point in the critical phase 2 trial destinY-Breast01 for treatment of HER2-positive metastatic breast cancer patients According to the press release, DS-8201 has the potential to become a new treatment for breast cancer patients who have received at least two pre-HER2 targeted therapies DS-8201 is an innovative ADC that targets HER2 receptors, connecting the all-human izede monoclonal antibody trastuzumab with a new type of topological isomorphase 1 inhibitor through a quadpeptide joint This ADC connects more cytotoxins to antibodies, which may have a better effect on killing tumors In 2017, the ADC was approved by the FDA as breakthrough therapy for the treatment of PATIENTs with HER2-positive, locally advanced or metastatic breast cancer In October, the FDA accepted the DS-8201 Biologics License Application (BLA) and granted it priority review The dS-8201 significantly reduced the size of a patient's tumor (Photo: NEJM) A key Phase 2 clinical study involving 184 patients received an average of six pre-therapies, including ado-trastuzumab emtansine (T-DM1), trastuzumab, pertuzumab, and others The results showed an objective remission rate (ORR) of 60.9 percent and a disease control rate (DCR) of 97.3 percent in patients treated with DS-8201 The median remission time (DOR) was 14.8 months and the median progression-free survival (PFS) was 16.4 months Cross the finish line! DMD Innovative Therapy Has Been Approved by the FDA Accelerated By the FDA, the FDA has announced accelerated approval of Sarepta Therapeutics' Vyondys 53 (golodirsen) to treat patients with Duhin's muscular dystrophy (DMD) patients who are suitable for treatment with exon 53 skipping These patients account for about 8% of the total number of DMD patients It is possible to treat most DMD patients through exosome jumps (Photo: Sarepta)Vyondys 53 is a phosphamide-derived oligonucleotide developed by Sarepta It targets the shearing process of the anti-myotrophin mRNA precursor, introducing anexformer 53 jump, designed to produce the short-cut but still functional anti-myotrophin The treatment is FDA-granted fast-track, orphan drug, and priority review Its approval gives Sarepta access to a rare childhood disease priority review voucher The efficacy of Vyondys 53 was evaluated in a two-part clinical study The first part included 12 DMD patients, 8 patients were treated with Vyondys 53 and 4 were given placebo treatment The second part is an open label trial that includes 12 patients in the first part and 13 new DMD patients In this study, the average myotrophin level in patients increased from 0.1% (baseline) to 1.02% of normal levels after treatment at 48 weeks The accelerated approval of Vyondys 53 is an alternative endpoint based on elevated myotrophy in the skeletal muscle of the patient under treatment The FDA believes that elevated myotrophin levels in the application may reasonably predict the clinical benefits of DMD patients At present, the clinical benefits of this treatment have not been confirmed As part of the accelerated approval, the FDA requires Sarepta to conduct clinical trials to verify the clinical benefits of this treatment Ongoing clinical studies will assess whether Vyondys 53 can improve motor function in DMD patients If clinical trials do not prove clinical benefits, the FDA may withdraw approval for the drug "Fearless" KRAS mutation! Keytruda single drug treatment NSCLC highlights "power" Mercadon (MSD) announced that anti-PD-1 therapy Keytruda as a single-drug first-line treatment of PD-L1-positive tumor (TPS 1%) of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), regardless of the patient's KRAS mutation status, can improve the total survival (OS), no survival progression (OS) and no objective relief (OS) These results are based on an exploratory analysis of key Phase 3 KEYNOTE-042 test data The purpose of exploratory analysis was to assess the prevalence of KRAS mutation populations and their correlation with efficacy in the KEYNOTE-042 trial Of the 1274 patients with primary treatment metastatic non-scaly NSCLC in the in-group UNDER-group KEYNOTE-042 and tumor expression PD-L1 (TPS-1%), 301 patients had KRAS-rated data: of which 232 patients did not have any KRAS mutations, 69 patients carried KRAS mutations, and 29 patients carried KRAS G12C mutations Other outcomes of this exploratory analysis (Photo: Mersadon.com) This exploratory analysis showed that Keytruda reduced the risk of death in patients with any KRAS mutation by 58% compared to chemotherapy (HR.42 .9 5% CI, 0.22-0.81)) to reduce the risk of death in patients with KRAS G12C mutationby by 72% (HR.28 (95% CI, 0.09-0.86) Keytruda's safety was consistent with the results observed in previously reported metastatic NSCLC patient studies Set cell lymphoma added "strong enemy"! Kite, a subsidiary of Gilead Sciences, announced that its CAR-T therapy KTE-X19, which targets CD19, has completely remissiond after one treatment in a trial for patients with recurrent/refractive enset cell lymphoma (MCL) Kite has filed a bioproduct licensing application (BLA) with the FDA If approved, KTE-X19 would be the first CAR-T treatment for MCL patients, the press release said KTE-X19 is an autonomous CAR-T therapy that targets CD19 It uses an XLP manufacturing process that includes T-cell screening and lymphocyte enrichment For some B-cell malignancies with signs of circulating lymphocytes, lymphocyte enrichment is a necessary step in the manufacture of CAR-T therapy CURRENTLY, KTE-X19 IS TREATING PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), CHRONIC LYMPHOCYTIC LEUKEMIA (CLL), AND MCL IN PHASE 1/2 CLINICAL TRIALS KTE-X19 has been approved by the FDA for breakthrough therapy and BYEMA-awarded PRIME drug recognition The research and development pipeline and progress of KTE-X19 (Photo Source: Kite Website) This BLA submission is based on positive clinical research data in Phase 2 called ZUMA-2 MCL patients who participated in the trial had received five pre-treatments, including chemotherapy, anti-CD20 monoclonal antibody therapy, BTK inhibitor ibrutinib or acalabrutinib, but the patient developed resistance or the disease returned The results showed that in 60 MCL patients who were able to assess efficacy, the total remission rate (ORR) reached 93%, of which 67% reached full remission (CR) At 12.3 months of median follow-up, 57% of patients' remission was still maintained Of the 28 patients who were initially treated (follow-up time was at least 24 months), 43% were still alive and in a state of ongoing remission without the need for additional treatment The 12-month progression-free survival rate and total survival rates are estimated at 61 per cent and 83 per cent, respectively Disease control rate 77%! Keytruda Triple Therapy Show The promising anti-cancer activity BioLineRx announced the results of a Phase 2a clinical trial of the BL-8040 developed by the company with the PD-1 antibody Keytruda, as well as chemotherapy, in combination with chemotherapy to treat patients with metastatic pancreatic cancer BL-8040 is a polypeptide antagonist that targets the chemofactor receptor CXCR4 The results show that this combination therapy shows a welcome anti-cancer activity in patients with metastatic pancreatic cancer The BL-8040 is a CXCR4 reverse agoniser with "best-in-class" features CXCR4 is a highly expressed trend factor receptor in many human cancers, and its high expression is associated with poor prognosis in patients Pre-clinical and clinical studies have shown that by inhibiting the function of CXCR4, BL-8040 can affect the transport of immune cells, effect T-cell tumor immersion, and reduce the immunosuppressive cells in the tumor microenvironment, thus turning "cold" tumors into "hot" A total of 36 patients participated in the phase 2a clinical trial called COMAT/KEYNOTE-202 as of December 5 this year ( photo: BioLineRx ) These patients had stage 4 metastatic pancreatic cancer and continued to progress after first-line chemotherapy The trial data showed that of the 22 patients who were able to receive a efficacy assessment, 7 achieved partial remission (PR), 10 achieved stable disease (SD), had a total remission rate (ORR) of 32% and disease control rate (DCR) was 77% This is better than the current second-line standard chemotherapy (17% ORR and 52% DCR) During treatment, five patients in a stable disease transitioned to partial remission as treatment continued, demonstrating the lasting effects of this combination Of the seven patients who received partial remission, five were still receiving treatment for a maximum duration of more than 330 days Originally: DMD innovative therapy accelerates crossing finish line; Keytruda triple therapy shows promising anti-cancer activity