January 2021 - Failed clinical study TOP5

On January 4, Calithera Biosciences announced that its main product, the glutamine enzyme inhibitor Teleglenastat (CB-839), had failed to reach its main endpoint in CANTATA clinical trials in patients with advanced or metastatic renal cell carcinoma (RCC).
calA shares fell 45 per cent on the day and announced 35 per cent job cuts.
Teleglenastat is a glutamine inhibitor.
In this study, 444 patients with advanced or metastasis RCC were recruited, all of them having previously received first- or two-line system therapy (including at least one vascular endothrotypy growth factor (VEGF) or a combination therapy of Navuliyu monoantigen and ipimu monoantigen), with the primary endpoint being progressive survival (PFS) as determined by an independent review of blind methods.
results showed that there was no significant difference in PFS (9.2m VS 9.3m) between Telaglenastat and placebo combined cabotini, thus missing the main finish line.
security is similar to using cabotinib alone.
Based on the strong scientific evidence of the use of Teleglenastat in patients with KEAP1/NRF2 mutant non-small cell lung cancer, and the safety observed in CANTATA, Calithera President and CEO Susan Molineaux said it would continue to advance Theraglenastat's random KEAPSAKE trial to evaluate the results of Telaglenastat's treatment of non-small cell lung cancer in association with K.
decision to lay off staff is also a follow-up study, with Calithera Biosciences' cash, cash equivalents and investments of approximately $115 million as of December 31, 2020.
executives believe this is enough to keep the company running by 2022, including the release of interim data on the KEAPSAKE test and the completion of the current cystic fibrosis test by 2021.
addition to the CANTATA study, Telaglenastat is conducting phase II ENTRATA trials in RCC, KEAPSAKE II trials in KEAP1/NRF2 mutation lung cancer, and solid tumor phase II trials with palbociclib.
addition, the company still has two arginase inhibitors in clinical studies, interfering with amino acid metabolism is the company's CALA platform strategy.
Tumor metabolism accelerated, reproduction, metastasis requires energy participation, which also gave birth to the concept of energy metabolism treatment, including a variety of amino acid path, amino acid transport protein and mitochondrial, the previous IDO inhibitors are also representatives of the field, but ultimately is also folding sand, failed to hit the line.
2. SRP-9001 Treatment of Duchy Muscular Dystrophy (DMD) Phase II Study On January 7, Sarepta announced the results of part1 topline study in a clinical Phase II (Study 102) study of the gene therapy SRP9001 for the treatment of Duchy muscular dystrophy (DMD).
results showed that although the study met the main biological indicators of micromyotrophy protein expression at 12 weeks after treatment, the main functional endpoints of the improvement in the overall NSAA score at 48 weeks were not statistically significant.
, SRPT's share price fell 51.9 per cent and its $6.5bn market capitalisation evaporated.
ISD is a muscular dystrophy disease caused by mutations in the muscular dystrophy protein gene.
is an aggressive disease that usually causes death in early adulthood and is accompanied by serious complications, including heart or respiratory problems.
mainly affects boys, with about 1 in every 3,500 or 5,000 boys with DMD.
SRP-9001 is a research gene transfer therapy designed to transfer micromyotrophy protein encoding genes to muscle tissue to produce trace amounts of antimyotrogen protein.
Study 102 Study PART 1 is an ongoing, randomized, double-blind, placebo-controlled clinical trial designed to assess the safety, efficacy, and toadability of single-dose SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) in 41 patients.
12 weeks after receiving SRP-9001 (n-20) treatment compared to the baseline, the average expression rate of micromyotrogenic protein measured by protein brination was 28.1%, and the study reached the main biological endpoint (P.lt;0.0001).
, participants treated with SRP-9001 had an increased total NSAA score at 48 weeks compared to placebo.
, the difference is not statistically significant (P s 0.37).
At each measuring point in time, participants who received SRP-9001 performed better than the placebo group, and at 48 weeks, participants in the treatment group showed a statistically significant 1.7 statistically significant increase in NSAA scores compared to the baseline (The total NSAA score increased by 0.9 points compared to the baseline for participants in the placebo group, which was statistically meaningless (n=21, P=0.1411).
results of the study 102 strengthened the good safety and tolerance of the SRP-9001 and found no new safety signals.
consistent with previously reported clinical data, clinical complement activation was not observed.
85 percent of the subjects in the treatment group experienced at least one adverse treatment-related event, compared with 43 percent in the placebo group.
Of the participants with treatment-related adverse events, 82% were mild or moderate severity, and 4 participants experienced severe adverse treatment-related events, including 3 participants in the treatment group (2 cases of transverse myolysis, 2 cases of transaminase elevation) and 1 participant in the placebo group (transverse muscle dissolution).
3. Troriluzole's Phase II/III Study for the Treatment of Alzheimer's Disease (AD) On January 18, Biohaven Pharmaceuticals announced the completion of the key top-line data and critical secondary data analysis for the treatment of the mild and moderate Alzheimer's Disease Phase II/III clinical study (T2 Protect AD).
according to the Alzheimer's Assessment Scale-11 versions of the Cognitive Sub-Scale (ADAS-Cog) and the Clinical Dementia Scale Boxes Score Sum (CDR-SB), mild-moderate treatment was treated at 48 weeks In the AD patient study, Troriluzole and placebo showed no significant difference compared to placebo controls in pre-set common primary endpoints and key secondary measurements (sea mass, assessed by magnetic resonance imaging (MRI).
However, a subgroup analysis of patients with mild AD showed that, although there was no significant numerical difference compared to placebo in week 48, troriluzole had potential benefits in ADAS-cog scale scores and MIR-assessed sea mass volume.
the average change in the volume of the sea mass in patients treated with troriluzole for mild AD (n=48) was -1.1% compared to the baseline, while the value of the placebo group (n=49) was -1.6% (p=0.2).
While data from ADAS-cog and haima MRI measurements in mild AD patients show that troriluzole has potential efficacy in early AD patients, additional analysis and biomarker data are needed to determine whether further research on early AD is necessary.
Troriluzole is a 3rd generation prebiotic drug developed by Biohaven that mediates glutamate, primarily by enhancing the expression and function of excitatory glutamate transporter on glial cells and increasing the re-intake of glutamate in synapses to reduce glutamate levels in synapses.
study, subjects were given 280 mg of troriluzole daily with good tolerance, consistent with previous studies.
's not Troriluzole's first defeat.
last year, in a 12-week Study of Phase II/III Obsessive Compulsive Disorder, troriluzole also failed to reach its primary endpoint, and the Clinical Phase III study of General Anxiety disorder failed.
, Biohaven CEO Dr. Vlad Coric said more biomarker data and other secondary analysis data are being waited to help determine whether troriluzole can benefit early AD patients.
but in general, the hope of success has faded.
4. Bintrafusp alfa Treats NSCLC Phase III Study January 20, German Merck and co-owner Glaxo announced that its PD-L1/TGFb fusion protein bintrafusp alfa (M7824) Phase III (INTR@PID Lung 037) interim analysis showed that it was not possible to beat Mercadon's PD-1 antibody, Trutruda.
, on the recommendation of the Independent Data Monitoring Board, Merck decided to terminate the study because it was unlikely to reach a common primary endpoint, particularly a non-progressed lifetime.
INTR@PIDLung 037 study is a multi-center, randomized, open, and controlled study designed to evaluate the efficacy of M7824 vs Pablic Pearl monoantigen therapy PD-L1 high expression late NSCLC.
a total of 584 subjects were recruited to receive static injection M7824 1200 mg every 2 weeks or 200 mg per 3 weeks until the disease progressed.
the main endpoints are progress-free and total lifetimes assessed by the Independent Review Board (IRC).
M7824 is a dual-functional fusion protein that recognizes the antibody structure (Y) that binds to PD-L1 at one end and TGF-β-β fusion protein (Trap) that binds to TGF-β, which simultaneously blocks both PD-L1 and TGF-β signaling path paths, relieving the immune system of inhibition and improving the immune system's inhibition of cancer cells.
the product is still in the process of a number of clinical studies, including cervical cancer, breast cancer, urethra skin cancer, BTC and so on.
5. GSK2831781 Phase II study for the treatment of active ulcerative colitis On January 22, Australian biotechnology Immutep announced that one of its partners, GlaxoSmithKline's research and development team, had discontinued GSK2831781's Phase II proof-of-concept study on active ulcerative enteritis.
GlaxoSmithKline made the decision after completing its scheduled mid-term analysis and discussing it with the Data Assessment Board, and is currently reporting, evaluating and analyzing the efficacy and safety data further, as well as evaluating the biological mechanisms to determine the next steps in the GSK2831781 development plan.
Immutep's collaboration with GSK remains valid, GSK2831781 From Immutep's IMP731 antibody, which is a cytotoxic antibody that depletes activated T cells and could theoretically be used to treat chronic autoimmune diseases, in addition to being studied for ulcerative colitis, which is evaluated for other autoimmune diseases.
GSK2831781 is also one of 14 important projects highlighted by GSK at the J.P. Morgan conference in the field of autoimmune and other diseases, and is another failed study following GSK's announcement that its PD-L1/TGFb fusion protein bintrafusp alfa (M7824) lost out at NSCLC.
between the two failed studies, the FDA's approval of GSK's long-acting, injectable HIV drug Cabenuva on January 21st was the biggest consolation for GSK's back-to-back losses.
LAG-3 (lymphocyte activation gene 3, LAG-3, CD223) is an immune checkpoint-subject protein that is mainly expressed in active T-cells, NK cells, B-cells, and plasma cell dendrine cells.
LAG-3 can be combined with MHC II molecules to reduce the activity of T cells.
, LAG-3 also enhances the inhibitory activity of regulatory T-cells (Tregs).
the use of therapeutic antibodies to inhibit LAG-3, can lift the inhibition of T cells, enhance the body's immune response.
6 January 2011, GSK and Immutep reached an agreement to receive a global exclusive development interest of 64 million pounds ($100 million, including down payments and mileage) from GSK2831781.
GSK will be subject to additional sales royalties if future products are available.
GSK is responsible for all costs associated with the clinical development and commercialization of GSK2831781.
Immutep is a pioneer in the development of LAG-3 immunotherapy for cancer and autoimmune diseases, and in addition to GSK's GSK2831781, there are three other core LAG-3 products under study, including first in class antigen delivery cells (A PC) activator Eftilagimod Alpha (LAG-3 fusion protein, in collaboration with Pfizer, Merca East, Eton, Eton), tumor-directed ieramilimab (which has granted global rights to Novarma), and LAG-3 agonist IMP761 intended for use in autoimmune diseases.
GSK's termination of GSK2831781's ulcerative enteritis Phase II project will not affect Immutep's plans for the development of three other products.