As usual, it was a busy week for clinical trial updates. Here’s a look.
As usual, it was a busy week for clinical trial updates. Here’s a look.
Merck and Bayer’s vericiguat met the primary efficacy endpoint in the Phase III VICTORIA trial in patients with worsening chronic heart failure. Vericiguat is a soluble guanylate cyclase (sGC) stimulator. The drug decreased the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when dosed in combination with available heart failure therapies.
Foamix Pharmaceuticals announced it had completed enrollment in its Phase II trial of FCD105 for moderate-to-severe acne vulgaris. FCD105 is a topical combination foam of 3% minocycline and 0.3% adapalene. The trial enrolled 400 patients, aged 12 years and older, with moderate-to-severe acne vulgaris. It is being conducted at multiple U.S. locations.
Iterum Therapeutics completed enrollment in its SURE 2 clinical trial of sulopenem in complicated urinary tract infections (cUTI). Sulopenem is a novel penem anti-infective compound with both oral and intravenous formulations. It is effective against a wide range of gram-negative, gram-positive and anaerobic bacteria resistant to other antibiotics. The multi-center, double-blind trial is measuring efficacy, tolerability, and safety of IV and oral sulopenem for cUTI in adults.
Karuna Therapeutics announced results from its Phase II trial of KarXT for acute psychosis in patients with schizophrenia. The drug showed a statistically significant and clinically meaningful 11.6-point mean reduction in total Positive and Negative Syndrome Scale (PANSS) score compared to placebo.
Novartis announced new subgroup analyses from its global Phase III PARAGON-HF study of patients with heart failure with preserved ejection fraction (HFpEF). The data suggest that in specific subgroups, receiving Entresto may cause greater decreases in heart failure hospitalizations and cardiovascular death compared to valsartan. The most benefit was observed in women with HFpEF and in HFpEF patients who were recently hospitalized for heart failure.
Caladrius Biosciences presented results from then ESCaPE-CMD trial of CLBS16 at the American Heart Association Scientific Sessions 2019. CLBS16 is the company’s autologous CD34+ cell therapy. The data demonstrated highly statistically significant improvement in coronary flow reverse correlating with symptom relief in patients with coronary microvascular dysfunction after a single intracoronary injection of CLBS16.
Amgen announced new analysis from the Repatha (evolocumab) cardiovascular outcomes FOURIER study. The trial evaluated the effectiveness of Repatha in patients who had a recent myocardial infarction (MI). The data showed patients who had a recent MI were at a higher risk of subsequent cardiovascular events compared to patients who had an MI over a year ago. They found that the risk of heart attack, stroke or CV death in this group of patients receiving Repatha was 25% compared to 15% in patients with a more distant MI.
The company, with Cytokinetics and Servier also announced new data from COSMIC-HF, a Phase II trial of omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF). In addition to previously reported improvements in cardiac contractility measures, the study found that measures of diastolic function were not different from placebo, and for some measures, trended toward improvement.
Adaptimmune updated data from patients with synovial sarcoma in the ongoing Phase I trial of ADP-A2M4. Of the 14 patients with s synovial sarcoma who have been treated in the expansion phase and have post-baseline scans, seven to date had clinical responses representing an overall response rate of 50%. Thirteen patients showed clinical benefit with best overall responses of PR or stable disease.
Myovant announced that its Phase III HERO trial relugolix met its primary endpoint and six key secondary endpoints in advanced prostate cancer. Relugolix is a once-daily, oral gonadotropin-release hormone (GnRH) receptor antagonist that decreases testicular testosterone production. In analysis of the responders, 96.7% of men receiving relugolix achieved sustained testosterone suppression to castrate levels. The company defined “responder” as achieving and maintaining testosterone suppression to less than or equal to 50 ng/dL from Week 5 through Week 48.
Five key secondary endpoints that were hit included superiority to leuprolide acetate, including rapid suppression of testosterone at days 4 and 15, profound suppression of testosterone at Day 15, rapid suppression of prostate-specific antigen (PSA) at Day 15, and suppression of follicle-stimulating hormone (FSH) at Week 24. The drug also showed non-inferiority to leuprolide acetate on sustained testosterone suppression through 48 weeks.
CRISPR Therapeutics and Vertex Pharmaceuticals announced positive interim data from the first two patients in the companies’ ongoing Phase I/II clinical trials of its CRISPR/Cas9 gene-editing therapy CTX001. One of the patients with transfusion-dependent beta thalassemia (TDT) was treated with CTX001 in the first quarter of 2019. The data reflects nine months of safety and efficacy follow-up. The second patient has severe sickle cell disease (SCD) and received CTX001 in mid-2019. The interim data is for four months of safety and efficacy follow-up. Nine months after CTX001 infusion, the TDT patient was transfusion independent. Total hemoglobin levels were 11.9 g/dL, 10.1 g/dL fetal hemoglobin, and 99.8% F-cells. Thirty days after CTX001 infusion, the SCD patient reached neutrophil and platelet engraftment. Four months after treatment, the patient was free of VOCs and had total hemoglobin levels of 11.3 g/dL, 46.6% fetal hemoglobin, and 94.7% F-cells.
AstraZeneca announced new data from five more analyses of the Phase III DAPA-HF trial. The data showed that Farxiga (dapagliflozin) decreased the risk of the primary composite outcome of worsening heart failure, defined as hospitalization or an urgent visit, or death from cardiovascular causes, compared to placebo, when added to standard of care. All across all five analyses, Farxiga showed improvements compared to placebo.
The Medicines Company announced data from ORION-10, the second of three 19-month Phase III trials of inclisiran for lowering cholesterol. Inclisiran is an investigational twice-yearly drug to reduce low-density lipoprotein cholesterol (LDL-C). It is the first and only in the small-interfering RNA (siRNA) class. The ORION-10 trial met all primary and secondary efficacy endpoints. The drug demonstrated placebo-adjusted LDL-C decreases of 58% at day 510 and showed time-averaged placebo-adjusted LDL-C decreases of 56% from day 90 through day 540.
Bristol-Myers Squibb announced results from one of the co-primary endpoints from its Phase III CheckMate -915 clinical trial looking at Opdivo and Yervoy in combination compared to Opdivo alone for the adjuvant treatment of complete surgical removal of stage IIIb/c/d or stage IV melanoma. The drug combination did not hit the co-primary endpoint of recurrence-free survival (RFS) in patients whose tumors expressed PD-L1 greater than 1%. However, the Data Monitoring Committee recommended the company continue the study with no changes. It will remain double-blinded and continue to investigate the other co-primary endpoint of RFS in the all-comer, intent-to-treat population.
Spring Bank Pharmaceuticals initiated dosing patients in its Phase I trial of SB11285. The drug is an intravenously administered STING agonist. The trial is being designed to evaluate safety, tolerability and initial anti-tumor activity of the drug in patients with advanced solid tumors.
Seelos Therapeutics dosed the first subjects in a Phase I Drug-Drug Interaction (DDI) study. SLS-002-191 is a single-center, open-label trial of SLS-002 in combination with two commonly prescribed antidepressants. SLS-002 is an intranasal racemic ketamine formulation. The study will enroll 48 healthy volunteers and evaluate over two weeks two treatment arms with a combination of SLS-002 and either venlafaxine ER or sertraline.
BrainStorm Cell Therapeutics published the results of its Phase II clinical trial of a single transplantation of autologous bone-marrow derived MSC-NTF cells (NurOwn) in ALS patients. The trial enrolled 48 patients randomized 3:1 at three U.S. sites. The trial confirmed that a single transplantation of NurOwn cells was safe and well-tolerated.
Sierra Oncology initiated a Phase III MOMENTUM trial of momelotinib in myelofibrosis. Momelotinib is a JAK1, JAK2 and ACVR1 inhibitor. The trial is expected to enroll 180 myelofibrosis patients who are symptomatic, anemic and have been previously treated with a JAK inhibitor.
Medsenic completed recruitment of all patients planned for its Phase II clinical trial. The study is evaluating Arscimed for chronic graft versus host disease (GvHD). The objective of the trial is to determine an optimal benefit/risk ration for IV treatment with a positive partial and/or complete response rate at six months after cGvHD diagnosis. Arscimed’s pharmacologically active ingredient is arsenic trioxide.
Elysium Health completed enrollment of its clinical trial of Basis on liver fat accumulation in healthy adults with nonalcoholic fatty liver (NAFL). Basis is a combination of the company’s proprietary nicotinamide riboside (NR) and pterostilbene (PT), which is designed to increase NAD+ levels and activate sirtuins. One hundred and eleven patients with NAFL ages 18-70 have been enrolled in the double-blind, placebo-controlled, randomized trial. It is expected to be completed in April 2020.
Spark Biomedical opened patient enrollment in its clinical trial to validate its auricular neurostimulation device for opioid withdrawal relief, currently named Phoenix. The company partnered with CARMAhealth, a specialty outpatient and primary care practice focused on addiction medicine. Patients with opioid use disorder (OUD) will enroll in the trial at two locations in Austin, Texas, and Lake Worth, Florida.
VBL Therapeutics announced data from its Phase II trial of VB-111 in recurrent glioblastoma (rGBM). VB-111 is a first-in-class, targeted anti-cancer gene-therapy agent developed for a wide range of solid tumors. The primary endpoint of the trial is an immunological readout and whether VB-111 can result in an increase in tumor infiltrating T lymphocyte (TIL) within the rGBM tumor. The drug demonstrated objective response, with VB-111 responders having a survival advantage.
