Clinical Catch-Up: July 26-30
With the Alzheimer’s Association International Conference (AAIC) conference last week, there were plenty of clinical trial news and updates. Here’s a look.
COVID-19-Related
Claritas Pharmaceuticals reported that a study led by clinicians at Royal Brompton & Harefield NHS Foundation Trust validated the potential of its nitric oxide releasing compound, R-107, as a possible treatment for coronavirus and COVID-19 infection. In the study, inhaled nitric oxide significantly improved oxygen levels given to patients with severe COVID-19 pneumonia.
Moderna announced that as it continues its study of its COVID-19 vaccine in children ages 5 to 11, it is expanding the study to include evaluations of rare side effects, including heart inflammation (myocarditis and pericarditis). This will likely push back EUA for this population until the end of this year or early 2022.
eFFECTOR Therapeutics dosed the first patient in a Phase Ib trial of zotatifin in mild to moderate COVID-19. Zotatifin is a potent and sequence-selective inhibitor of eukaryotic translation initiation factor 4A mediated translation.
Non-COVID-19-Related
Abeona Therapeutics announced magnetic resonance imaging (MRI) data from its Phase I/II Transpher A trial in San Filippo Syndrome Type A (MPS IIIA). MPS IIIA is a rare, fatal disease of lysosomal storage. ABO-102 is a novel gene therapy. It is a one-time intravenous infusion. It uses a self-complementary AAV9 vector to transport a functional copy of the SGSH gene to CNS and peripheral organ tissues. The MRI data demonstrated that ABO-102 increased grey matter, corpus callosum and amygdala volumes in the brain. The results were in three pediatric patients with MPS IIIA. The results were observed at 24 months and compared to afflicted patients who did not receive the treatment.
INmune Bio announced the design of its upcoming Phase II trial of XPro in patients with mild Alzheimer’s disease. The announcement came with the release of additional biomarker data from the Phase Ib AD trial that demonstrated improvement in white matter (myelinated axons) that degenerate in AD patients. XPro or Xpro1595 is a next-generation inhibitor of tumor necrosis factor (TNF) that uses a dominant-negative TNF technology. Pegipanermin neutralizes soluble NTF without affecting trans-membrane TNF or TNF receptors.
F-star Therapeutics provided an interim update on its first-in-human dose-escalation study of SB 11285 in advanced solid tumors. SB 11285 is a second-generation STING agonist. The drug was well tolerated alone and in combination with atezolizumab across all dose levels.
Eledon Pharmaceuticals received a go-ahead from Health Canada to start a Phase I study of AT-1501 as a replacement for tacrolimus as an immunosuppressive regimen in patients undergoing kidney transplantation. It will be a multicenter, open label study in six to 12 subjects.
MediWound initiated a Phase I/II trial of MW005 for low-risk Basal Cell Carcinoma (BCC). In parallel, an investigator-initiated Phase II trial of the drug in non-melanoma skin cancers is being run at the Soroka Medical Center in Israel. MW005 is a proprietary formulation designed to ease self-administration, and is based on the active substance in NexoBrid and EscharEx, a concentrate of proteolytic enzymes enriched in bromelain.
Allergan, an AbbVie company, announced new data, including the full results of the Phase III GEMINI 1 trial of AGN-190583 (pilocapine 1.25%) ophthalmic solution for presbyopia. The drug met both its primary and key secondary efficacy endpoints, with patients hitting near and intermediate vision gains.
Denali Therapeutics announced additional positive data from a Phase I/II trial of ETV:IDS (DNL310) for Hunter syndrome (MPS III). ETV:IDS is a brain-penetrant enzyme replacement therapy designed to treat CNS and peripheral manifestations of the disease.
Cognito Therapeutics presented new clinical data from its lead digital therapeutic candidate in Alzheimer’s disease. This included data on gamma frequency neuro-modulation on cognitive function, which demonstrated improvements in sleep, improvements in memory and cognition, and decreased brain atrophy and volumetric loss.
Biogen and Ionis Pharmaceuticals announced topline results from a Phase Ib clinical trial of BIIB080/MAPTRX. The drug is an investigational antisense therapy that targets microtubule-associated protein tau (MAPT) mRNA and prevents production of tau protein. The Phase Ib study of BIIB080/MAPTRX hit the primary objective of safety and tolerability in mild Alzheimer’s. It also showed robust time and dose dependent decreases of tau protein in cerebrospinal fluid (CSF) in these patients over the three-month treatment period as well as sustained reductions in the six-month post-treatment period.
Patients receiving the drug demonstrated dose-dependent decreases in total-tau concentration in CSF eight weeks after the last dose with a mean percentage reduction of 30%, 40% and 49% in the low, medium and high dose cohorts who were treated every four weeks, and 42% in the cohort treated every 12 weeks.
Merck announced positive data from the KEYNOTE-355 Phase III trial of Keytruda (pembrolizumab) with chemotherapy in metastatic triple-negative breast cancer. The combination demonstrated a statistically significant and clinically meaningful improvement in overall survival compared to chemotherapy alone.
BioVie presented data from a Phase III trial of NE3107 in Alzheimer’s. NE3107 is an oral small molecule, blood-brain permeable anti-inflammatory insulin sensitizer that binds ERK. The data highlighted its safety profile and broad mechanism of action against features of Alzheimer’s disease.
Kronos Bio reported the FDA had cleared its IND for lanraplenib for r/r FLT3-mutated acute myeloid leukemia in combination with gilteritinib in a Phase I/II trial. It is expected to launch in the fourth quarter. Lanraplenib is a next-generation spleen tyrosine kinase (SYK) inhibitor.
Disc Medicine initiated a Phase I trial of DISC-0974 for modulating iron metabolism and red blood formation in anemia of inflammation. DISC-0974 is a first-in-class inhibitor of hemojuvelin (HJV).
Genentech, a Roche company, published data from FIREFISH Part 2, a global study of Evrysdi (risdiplam) in babies ages 1-7 months old with symptomatic Type 1 spinal muscular atrophy (SMA). It hit the primary endpoint with 29% sitting without support for at least five seconds by month 12.
Satsuma Pharmaceuticals randomized the first patient in its SUMMIT Phase III trial of STS101 for acute treatment of migraine. STS101 is proprietary nasal powder formulation of the anti-migraine drug dihydroergotamine mesylate (DHE).
Orchestra BioMed presented long-term follow-up data on hypertensive patients from the control group of the MODERATO II study who received crossover treatment with BackBeat Cardiac Neuromodulation Therapy. The data showed a clinically meaningful and statistically significant decrease in blood pressure.
Karyopharm Therapeutics dosed the first patients in two Phase II and I/II trials of XPOVIO (Selinexor) in advanced melanoma and in patients with treatment-naïve myelofibrosis. The drug is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound in combination with approved therapies.
ALX Oncology and Merck dosed the first patient in the Phase II ASPEN-04 trial of ALX148 and Merck’s Keytruda (pembrolizumab) and standard chemotherapy for advanced head and neck squamous cell carcinoma. ALX148 is a next-generation CD47 blockers. Keytruda is an anti-PD-1 checkpoint inhibitor.
Arcturus Therapeutics received approval from the UK Health Research Authority to start a Phase II trial of ARCT-810 for Ornithine Transcarbamylase (OTC) Deficiency. ARCT-810 is a novel mRNA-based therapeutic candidate.
Reneo Pharmaceuticals dosed the first patient in the STRIDE Phase IIb study of REN001 for patients with primary mitochondrial myopathies (PMM). REN001 is a potent and selective agonist of the peroxisome proliferator-activated receptor delta receptor.
HUTCHMED and AstraZeneca initiated a Phase II trial of Orpathys (savolitinib) in advanced or metastatic MET amplified gastric cancer or adenocarcinoma of the gastroesophageal junction. Salvolitinib is an oral, potent, and highly selective small molecule MET inhibitor, a receptor tyrosine kinase.
SCYNEXIS presented data from its Phase III VANISH Program on oral ibrexafungerp for vulvovaginal candidiasis (VVC), also known as vaginal yeast infection. The data demonstrated strong efficacy and a favorable tolerability profile.
AC Immune presented data from the Phase Ib trial of anti-Abeta (beta-amyloid) vaccine ACI-24 in adults with Down syndrome. The results showed the drug was safe and tolerated in adults with Down syndrome. Down syndrome individuals are susceptible to Alzheimer’s disease. Beta-amyloid accumulation in the brain is linked to Alzheimer’s disease.
Progenity announced successful completion of the validation study of its Preecludia rule-out test for preeclampsia. The PRO-104 study was a prospective, multi-center, observational study with more than 1,300 enrolled subjects. Test specimens were collected from pregnant patients aged 18 to 45 years and 28 0/7 to 36 6/7 weeks’ gestational age.
Eli Lilly and Company presented data analysis from the Phase II TRAILBLAZER-ALZ study that supports the argument that decreases in beta-amyloid in Alzheimer’s disease slows cognitive decline. Lilly’s data is two exploratory analyses from the TrailBLAZER-ALZ trial of their own monoclonal antibody, donanemab. It targets a modified form of beta-amyloid plaque known as N3pG. In one analysis, they found that larger changes to amyloid plaques after treatment with donanemab was “highly associated with less cognitive decline.” In addition, the patients with the most plaque clearance at 24 weeks also had less progression of yet another abnormal protein found in Alzheimer’s patients, tau. The second analysis demonstrated that donanemab resulted in a rapid decrease of a biomarker that is associated with Alzheimer’s pathology, plasma P-tau217, which was observed within 12 weeks.
Cyclo Therapeutics announced new data from its Phase I extension trial of Trappsol Cyclo for Niemann-Pick Disease Type C1. The drug is a proprietary formulation of hydroxypropyl beta cyclodextrin with an affinity for cholesterol. The data demonstrated continuing safety and efficacy trends.
Revolo Biotherapeutics was granted authorization in the UK to runa Phase II allergen sensitivity study of ‘1104, its first-in-class peptide for treatment of allergic disease. The peptide is derived from a natural immune-regulatory protein, mTB Chaperonin 60.1.
Orchestra BioMed announced long-term follow-up data on hypertensive patients from the control group of the MODERATO II study who received crossover treatment with BackBeat Cardiac Neuromodulation Therapy. The data showed a clinically meaningful and statistically significant reduction in blood pressure.
Vaxart announced that its oral tablet vaccine platform successfully boosted immune responses in patients previously vaccinated with a Vaxart oral vaccine more than a year earlier. The data is from the company’s 12-subject Phase Ib blinded study of its norovirus vaccine.
Annovis Bio presented efficacy data from two Phase IIa trials of ANVS401 (posiphen) for cognition in Alzheimer’s and motor function in Parkinson’s disease. The data demonstrated a 30% improvement in cognition after 25 days of treatment. They also presented data showing that the drug decreases cytotoxic cascade.