Clinical Catch-Up: February 10-14
It was a very busy week for clinical trial news. Here’s a look.
Kodiak Sciences announced positive safety, efficacy and durability data from its ongoing Phase Ib trial of KSI-301 in wet age-related macular degeneration (AMD), diabetic macular edema (DME) and retinal vein occlusion (RVO). KSI-301 is an intravitreal anti-VEGF antibody biopolymer conjugate. They describe the data as promising with 420 doses in 130 patients.
vTv Therapeutics announced positive data from Part 2 of the Phase II Simplici-T1 trial of TTP399 in type 1 diabetes. TTP399 is a novel, liver-selective glucokinase activator. The 12-week trial studied the efficacy and safety of 800 mg of TTP399 compared to placebo in 85 people with type 1 diabetes on optimized insulin therapy. It hit its primary objective, demonstrating statistically significant improvements in HbA1c compared to placebo.
Regeneron Pharmaceuticals announced positive two-year results from the Phase III PANORAMA trial of Eylea (aflibercept) in moderately severe to severe non-proliferative diabetic retinopathy (NPDR). The data showed that untreated moderately severe and severe NPDR can lead to vision-threatening events, and Eylea was shown to reduce the likelihood of these events by at least 75% compared to more than half of the patients (58%) in the untreated sham arm developed a VTC or center-involved diabetic macular edema (CI-DME) within two years.
Roche’s Genentech and Eli Lilly’s different drugs failed the same Alzheimer’s clinical trial. DIAN-TU-001 is a Phase II/III trial that tested two therapies compared to placebo, Genentech and Roche’s gantenerumab and Eli Lilly and Company’s solanezumab.
The overall trial was founded in 2010 and funded by Eli Lilly and Company, Roche and Genentech, the National Institutes of Health, and other donors. The trial was sponsored by Washington University School of Medicine in St. Louis. Genentech announced that the gantenerumab arm of the Phase II/III DIAN-TU-001 trial did not meet the primary endpoint in an early-onset, inherited form of Alzheimer’s. This form of Alzheimer’s is known as autosomal dominant AD (ADAD) and makes up less than 1% of cases. Eli Lilly and Company’s solanezumab also failed to meet the primary endpoint. Solanezumab is also an antibody against amyloid.
Oculis reported positive data from a Phase II trial of OCS-01 for diabetic macular edema (DME). OCS-01 is a novel eye drop formulation of dexamethasone, developed using the company’s Soluble NanoParticle technology. The trial met its efficacy endpoints, showing that OCS-01 was more effective than vehicle in reducing central macular thickness and improving visual acuity.
Myovant announced its Phase III LIBERTY open-label extension study of relugolix combination therapy for uterine fibroids was positive. The drug is a combination of relugolix, estradiol and norethindrone acetate. It showed an 87.7% response rate at one year while maintaining bone mineral density. It expects to include the data in its NDA for heavy menstrual bleeding associated with uterine fibroids expected in April 2020.
Alkahest launched a Phase IIb trial of AKST4290 in treatment native wet age-related macular degeneration. AKST4290 is a small molecule CCR3 inhibitor that can be dosed orally. The company dosed the first patient, which will determine the effects of the drug on visual acuity.
Bold Therapeutics received clearance from Health Canada to initiate a Phase Ib trial of BOLD-100 in combination with FOLFOX for gastric, pancreatic, colorectal and bile duct cancers. BOLD-100 is a first-in-class anti-resistance therapeutic that appears to improve the activity of a wide range of other anti-cancer drugs by disabling a critical and previously untargeted resistance, survival and proliferation pathway common across cancers.
Intellia Therapeutics presented new data from two of its programs for NTLA-5001 for treatment of acute myeloid leukemia (AML). NTLA-5001 is an engineered T-cell therapy utilizing a T-cell receptor-directed approach to target Wilms’ Tumor 1 (TWT1) intracellular antigen for AML. The data showed that the selection of a natural, high-affinity TRC, in combination with CRISPR-enabled engineering and targeted insertion, results in an engineered T-cell that can kill primary AML blasts.
Biohaven Pharma reported negative topline data from its Phase III trial of troriluzole compared to placebo for Generalized Anxiety Disorder (GAD). The trial looked at 402 adults at more than 45 centers in the U.S. The drug as a monotherapy twice a day did not differentiate from placebo on the mean change from baseline on the Hamilton Anxiety Rating Scale (HAM-A) after eight weeks of treatment.
City of Hope, Dana-Farber Cancer Institute and MD Anderson Cancer Center reported that a Phase II clinical trial of a Triplex vaccine to prevent cytomegalovirus reduced the rates of CMV complications in transplant recipients by 50%. The trial enrolled 102 people who had undergone an allogeneic hematopoietic stem cell transplant, with half receiving Triplex, developed by City of Hope researchers.
TriSalus Life Sciences initiated a Phase I trial of its Pressure-Enabled Drug Delivery (PEDD) approach with standard of care system chemotherapy. PEDD with SmartValve technology is a self-expanding, one-way micro-valve that allows optimal infusion pressures for deeper therapeutic penetration. The trial will be conducted at Roger Williams Medical Center in patients with unresectable pancreatic adenocarcinoma and enroll nine patients.
Adverum Biotechnologies announced new interim data from the OPTIC Phase I dose-ranging trial of ADVM-022 intravitreal injection gene therapy for wet age-related macular degeneration (ADM). The drug showed a robust efficacy signal and evidence of a dose response in both cohorts. ADVM-022 uses a proprietary vector capsid, AAV.7m8, which carries an aflibercept coding sequence under the control of a proprietary expression cassette. It is administered as a one-time intravitreal injection.
Astellas Pharma and Pfizer reported results of the final overall survival (OS) analysis from the Phase III PROSPER trial of Xtandi (enzalutamide) plus androgen deprivation therapy compared to placebo plus ADT in non-metastatic castration-resistant prostate cancer (nmCRPC). The data showed a statistically significant improvement in OS in patients receiving the drug and ADT. OS was a key secondary endpoint. In 2018, the companies reported the PROSPER trial met its primary endpoint of metastasis-free survival (MFS).
Exelixis’ Cabometyx (cabozantinib) showed promising Phase I results in prostate cancer with cabozantinib in combination with Genentech’s checkpoint inhibitor Tecentriq (atezolizumab). Exelixis announced positive results from the metastatic castration-resistant prostate cancer (CRPC) cohort of COSMIC-021, the Phase Ib trial of Cabometyx and Tecentriq in patients with locally advanced or metastatic solid tumors.
The interim analysis included 44 patients with a median follow-up of 12.6 months. The objective response rate (ORR), the trial’s primary endpoint, was 32%, including two complete responses and 12 partial responses. The disease control rate came in at 80%. In 36 patients with high-risk clinical features that included visceral metastases and/or extra-pelvic lymph node metastases, the ORR was 33%.
The median duration of response for all patients that responded was 8.3 months. Of the 12 patients who had an objective response and at least one post-baseline prostate-specific antigen (PSA) evaluation, 67% showed their PSA dropped at least 50%.
LogicBio Therapeutics announced the FDA had placed a clinical hold on its IND submission for LB-001 for methylmalonic acidemia (MMA) pending the resolution of clinical and nonclinical questions. LogicBio submitted the IND in January 2020 to support the launch of the Phase I/II trial. LB-001 is an investigational pediatric genome editing therapy using the company’s GeneRid technology, that allows site-specific integration and presumably lifelong expression of therapeutic transgenes. It is designed to insert a functioning copy of the faulty human methylmalonyl-COA mutase (MMUT) gene into the genome of MMA patients.
Elicio Therapeutics and Natera plan to collaborate on a prospective, multicenter Phase I/II trial of ELI-002 in pancreatic ductal adenocarcinoma (PDAC) patients who have undergone neoadjuvant chemotherapy after pancreatectomy. ELI-002 is an Amphiphile immuno-oncology therapy targeting KRAS mutations. The IND submission for the 108-patient trial will open at 10-12 sites in the U.S. in the first half of this year.
NGM Biopharmaceuticals initiated a Phase Ia/Ib trial of NGM120 in cancer and cancer anorexia/cachexia syndrome (CACS). CACS is uncontrolled wasting of skeletal muscle and fat associated with cancer. NGM120 is a first-in-class antagonistic antibody that binds glial cell-derived neurotrophic factor receptor alpha-like (GFRAL), inhibiting growth differentiation factor 15 (GDF15) signaling.
Advaxis and Personalis are collaborating to leverage Personalis’ ImmunoID NeXT Platform in Advaxis’ ongoing Phase I/II ADXW-503 (HOT Lung) trial. The trial is studying ADXW-503 as a monotherapy and in combination with Merck’s Keytruda in non-small cell lung cancer (NSCLC). Under the deal, Personalis will run comprehensive tumor immunogenomic profiling to identify the predictive composite biomarkers and/or signatures of response as well as potential mechanisms of therapy resistance.
iCAD announced the first metastatic brain tumor was treated in the U.S. with intraoperative radiation therapy (IORT) using the Xoft Axxent Electronic Brachytherapy (eBx) System. It is the beginning of a clinical trial on IORT for patients with large brain metastases treated with neurological resection with the Xoft System. The Xoft System is FDA-cleared, CE marked and licensed in many countries for cancer treatment anywhere in the body. It utilizes a tiny x-ray source to deliver precise, concentrated doses of radiation directly to the tumor site.
Merck’s checkpoint inhibitor Keytruda (pembrolizumab) proved itself effective in yet another cancer indication. This time, the company announced positive results from the pivotal Phase III KEYNOTE-355 trial of Keytruda in combination with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC) whose tumors expressed PD-L1. The trial met one of its dual primary endpoints, progression-free survival (PFS).
Allena Pharmaceuticals reached agreement with the FDA on a streamlined design for URIROX-2, the second pivotal clinical trial of reloxaliase for severe hyperoxaluria. Reloxaliase is a potential first-in-class, non-absorbed, oral enzyme. The trial design incorporates adaptive design elements to allow changes to sample size and duration of treatment based on accrued kidney stone disease progression rates.
TLC completed its patient enrollment early in Part 2 of the TLC590 Phase II trial. The trial is evaluating TLC590 for postsurgical pain management after bunionectomy. TLC590 is a non-opioid, proprietary BioSeizer sustained release formulation fo ropivacaine.
Adamas Pharmaceuticals published the final results from a two-year open-label study showing that its Gocovri (amantadine) in Parkinson’s disease showed a sustained improvement in levodopa-induced dyskinesia (LID). The trial enrolled 223 patients. The research was published in the Journal of Parkinson’s Disease.
CicloMed presented two posters at the American Society of Clinical Oncology Genitourinary Cancer Symposium on new data from its Phase I trial of fosciclopirox. The data was analyzed in 19 advanced solid-tumor patients across eight dose cohorts, which gave them the Recommended Phase II Dose. The second poster describes the fosciclopirox Phase I expansion cohort in cisplatin-ineligible muscle-invasive bladder cancer (MIBC) patients.
Advaxis updated results from the combination arm of KEYNOTE-46 (Part B), the company’s ongoing Phase I/II trial of ADXS-PSA with Merck’s Keytruda in metastatic, castrate-resistant prostate cancer. ADXS-PSA is a Lysteria monocytogenes (Lm)-based immunotherapy. The survival data suggested the potential for meaningful increases in median overall survival.
SCYNEXIS completed patient enrollment ahead of schedule in the second pivotal Phase III (VANISH-306) trial of ibrexafungerp for vulvovaginal candidiasis (VCC), otherwise known as a vaginal yeast infection. Ibrexafungerp is a broad-spectrum, IV/oral antifungal.
Dana-Farber Cancer Institute presented data of a Phase I/II trial at the ASCO 2020 Genitourinary Cancers Symposium of MK-6482 in advanced clear cell kidney cancer. The study was in 55 patients who had an average of three previous treatment regimens. MK-6482 targets hypoxia-inducible factor (HIF)-2a, blocking cell growth, proliferation, and abnormal blood vessel formation. In their study, they reported a response rate of 24% across all risk categories of patients receiving the drug.
Janssen Pharmaceutical of Johnson & Johnson released interim data from the Phase IIIB STARDUST study of Stelara (ustekinumab) in Crohn’s disease. At week 16, 79% of patients with moderately to severely active Crohn’s disease achieved clinical response and 67% were in clinical remission. Stelara is a human IL-12 and IL-23 antagonist.
CytoDyn reported continued positive data from its mTNBC and MBC patients receiving leronlimab. Leronlimab is a CCR5 antagonist. The company updated information on five patients with metastatic triple-negative breast cancer (MTNBC) or metastatic breast cancer (MBC). They describe them as “extremely promising.”