Clinical Catch-Up: October 26-30
It was a particularly busy week for announcements about clinical trials, both related to COVID-19 and everything else. Here’s a look.
COVID-19-Related
AstraZeneca and the University of Oxford reported that their COVID-19 vaccine increases immune responses in older and younger adults against COVID-19. They also indicated that adverse events for AZD1222 were lower in the elderly volunteers than in the younger.
aTyr Pharma completed enrollment in its Phase II trial of ATYR1923 in COVID-19 patients with severe respiratory complications. ATYR1923 is a fusion protein made up of the immuno-modulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody. It is a selective modulator of neuropilin-2 that downregulates the innate and adaptive immune response in inflammatory diseases.
BioSig Technologies halted its signal finding Phase II trial of merimepodib in combination with IV remdesivir in adults with advanced COVID-19. This patient population was at high risk for dying from the disease. Although the most recent review suggested all 22 Grade 4 patients were discharged from the hospital and did not relapse in the 37-day follow-up period, in Grade 3 patients there was an imbalance in survival rates between the placebo and merimepodib that indicated it would be unlikely to hit its primary safety endpoints.
Biophytis dosed the first patient in Brazil in its Phase II/III trial of sarconeos in COVID-19-related respiratory failure. Sarconeos is a small molecule, oral compound being developed for treatment of neuromuscular diseases, including sarcopenia and Duchenne’s muscular dystrophy (DMD).
Eli Lilly halted a study of its LY-COV555 antibody against COVID-19 in hospitalized patients. About two weeks ago an independent Data Monitoring Committee paused enrollment in this trial because of a potential safety issue. The National Institute of Allergy and Infectious Diseases (NIAID), the study sponsor, could not verify the safety issue, but their analysis also indicated there was little likelihood the antibody would help the hospitalized patients.
Novavax provided an update on its Phase III COVID-19 vaccine trial. Of NVX-CoV2373. It presented data on its ongoing Phase I/II trial, including new Phase II reactogenicity data. It expects its US Phase III trial to be fully enrolled in November.
Aerpio Pharmaceuticals dosed its first patient in the Phase II trial of razuprotafib to prevent and treat acute respiratory distress syndrome (ARDS) in COVID-19 patients. Razuprotafib binds to and inhibits vascular endothelial protein tyrosine phosphatase (VE-PTP), an important negative regulatory of Tie2.
Pfizer and BioNTech indicated yesterday that its Phase III clinical trial of 44,000 volunteers now needs fewer than 2,000 people to be fully enrolled. The vaccine, which requires two doses about 28 days apart, has also fully dosed 36,000 people.
OncoSec got the FDA go-ahead to run its Phase I trial for CORVax12, a novel DNA-encodable vaccines against SARS-CoV-2 that the company is developing with Providence Cancer Institute. CORVax combines the company’s immuno-stimulant IL-12 expression platform, TAVO (tavokinogene telseplasmid), with a DNA-encodable stabilized trimeric SARS-CoV-2 spike glycoprotein developed by researchers at NIAID.
Equillium received the green light from the FDA to launch a Phase III EQUINOX trial of itolizumab in hospitalized COVID-19 patients with ARDS. They plan to begin enrolling in the fourth quarter with data in mid-year 2021. Itolizumab is a first-in-class monoclonal antibody that selectively targets the CD6-ALCAM pathway, which plays a central role in modulating the activity and trafficking of T cells that drive immuno-inflammatory diseases.
Non-COVID-19-Related
Novartis released promising interim Phase II data of iptacopan in C3 glomerulopathy (C3G). The analysis was presented at the virtual American Society of Nephrology (ASN) 2020 Annual Meeting. Iptacopan is a first-in-class oral, small molecule that inhibits factor B. Factor B is a key serine protease of the alternative pathway of the complement cascade. In the interim data analysis, after 12 weeks iptacopan significantly decreased proteinuria (protein in the urine) by 49% compared to baseline values. It was measured by 24-hour urine protein/creatinine ratio (UPCR) evaluation in 12 patients with C3G. The drug strongly inhibited alternative complement pathway activity and improved plasma C3 levels. It also stabilized renal function.
FibroGen presented data from two pooled analyses from its roxadustat global Phase III development program this weekend at the American Society of Nephrology (ASN) Kidney Week 2020 Reimagined conference. The analyses looked at associations between the hemoglobin (Hb) levels achieved and cardiovascular outcomes in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anemia of chronic kidney disease (CKD).
They analyzed six total trials, three in NDD patients and three in DD patients, and they showed that Major Adverse Cardiovascular Events (MACE; all-cause mortality, myocardial infarction, and stroke) and MACE+ (MACE plus heart failure or unstable angina requiring hospitalization) rates were highest when Hb was less than 8 g/dL, decreased as Hb rose, and were lowest when Hb levels exceeded 10 g/dL.
SeaStar Medical announced positive results from the first application of the Seleective Cytopheretic Device (SCD) in pediatric patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). No adverse events were observed and it met its endpoints of safety and reduced mortality and dialysis dependence at day 60. SSD is a medical device that employs immunomodulating technology to target pro-inflammatory neutrophils and monocytes during CRRT and remove the cytokine storm that causes severe inflammation and organ failure in critically ill patients.
RedHill Biopharma announced new data in support of Talicia as first-line therapy for eradication of H. pylori infection in adults. Talicia is a three-drug combination of omeprazole, a proton pump inhibitor, a penicillin-class antibacterial, and rifabutin, a rifamycin antibacterial.
PTC Therapeutics launched a registration-directed Phase II/III trial of vatiquinone (PTC743) in patients with mitochondrial epilepsy. This form of epilepsy is found in children with inherited mitochondrial disease. Vatiquinone is an oral small molecule that inhibits 15-Lipoxygenase, a key enzyme that regulates oxidative stress and inflammation response pathways found in many neurological diseases, including epilepsy.
Advaxis’ ADXS-503 with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) showed pronounced and sustained control in its ongoing Phase I/II non-small cell lung cancer (NSCLC) trial. ADXS-503 is the first drug construct from the company’s ADSX-HOT off-the-shelf, cancer-type specific, immunotherapy program. The combination had a disease control rate of 67% and overall response rate of 17% after immediate prior progression on Keytruda.
Mustang Bio presented initial Phase I trial data of one patient’s experience with MB-105, a prostate stem cell antigen (PSCA) chimeric antigen receptor (CAR) T therapy in PSCA-positive metastatic castration-resistant prostate cancer (mCRPC). On day 28, the patient demonstrated a 94% reduction in PSA, near complete reduction of measurement soft tissue metastasis by computed tomography, and improvement in bone metastases by MRI.
BioCardia published data from its initial open-label roll-in cohort for its ongoing CardiAMP Heart Failure (HF) Phase III trial. The data showed CardiAMP was well-tolerated in HF patients and demonstrated improved distance in six-minute exercise testing at six months. CardiAMP is a cell therapy made up of bone marrow mononuclear cell (BM MNC) enrichment and transendocardial injection of 200 million BM MNCs.
CytoDyn announced two patients have demonstrated noticeable signs of improvement after treatment with leronlimab in helping recover from stroke. Leronlimab is able to cross the blood-brain barrier and is a CCR5 antagonist, which has shown promise in various diseases processes.
Aileron Therapeutics announced new positive clinical data from its ongoing Phase Ib trial of ALRN-6924 prior to second-line topotecan administration. The data demonstrated a protective effect against severe anemia, thrombocytopenia and neutropenia in patients with p53-mutated small cell lung cancer (SCLC).
Galera Therapeutics presented an abstract containing interim data from the first 19 patients in its pilot Phase I/II trial of avasopasem manganese in combination with stereotactic body radiation therapy (SBRT) compared with SBRT and placebo in patients with locally advanced pancreatic cancer (LAPC). At the interim point, more than a year, median overall survival (OS) had not yet been reached in the avasopasem arm but was 40.4 weeks in the placebo arm. The avasopasem arm also demonstrated favorable progression-free survival.
Catabasis Pharmaceuticals announced that its Phase III PolarisDMD trial of edasolonexent in Duchenne muscular dystrophy (DMD) failed to hit the primary endpoint, which was change from baseline in the North Star Ambulatory Assessment (NSAA) over one year compared to placebo. The secondary endpoint also did not show statistically significant improvements. The company is halting activities related to the development of edasalonexent.
Dermavant Sciences presented data on its Phase III PSOARING trial of tapinarof cream in plaque psoriasis. Tapinarof is a potential first-in-class, steroid-free, cosmetically elegant, once-daily therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream. The data was presented at the European Academy of Dermatology and Venereology (EADV).
Rafael Pharmaceuticals crossed the enrollment of 100 patients in its Phase III Armada 2000 trial of devimistat in relapsed or refractory acute myeloid leukemia (AML). Devimistat is being tested in combination with high dose cytarabine and mitoxantrone (CHAM) compared to high dose cytarabine and mitoxantrone alone in older patients.
Syntrix Pharmaceuticals completed initial dosing in its Phase I/II trial of SX-682 in myelodysplastic syndromes and metastatic melanoma. They are also opening trials of the drug in pancreatic cancer, colorectal cancer and advanced tumors including breast and head and neck cancers. SX-682 is an oral allosteric small-molecule inhibitor of CXCR1 and CXCR2, a master switch of the immunosuppressive tumor microenvironment.
Scholar Rock announced positive six-month interim data from the TOPAZ Phase II clinical trial of SRK-015 in Type 2 and 3 Spinal Muscular Atrophy (SMA). The patients receiving the drug showed improvements in Hammersmith scale scores, the primary efficacy endpoint, in all three patient cohorts. SRK-015 is a selective inhibitor of the activation of myostatin.
Alzheon initiated a Phase II trial evaluating biomarker effects of ALZ-801 in Alzheimer’s disease. The drug is an oral therapy blocking formation of neurotoxic soluble amyloid oligomers.
GeneTx Biotherapeutics and Ultragenyx Pharmaceutical announced positive interim data from the Phase I/II trial of GTX-102 for Angelman syndrome. Preliminary data in five patients suggested substantial improvements in communication, behavior, sleep, gross motor and fine motor function. GTX-102 is an antisense oligonucleotide designed to target and inhibit expression of UBE3A-AS.
ATAI Life Sciences completed its pilot study designed to show nose to brain delivery of N-acetylcysteine (NAC) in healthy volunteers. They have also received approval to continue Phase I trial development from the FDA. NAC stimulates the synthesis of glutathione, the most abundant endogenous antioxidant, and is known to prevent oxidative damage to cells. It is being developed for intranasal delivery to patients with acute mild traumatic brain injury (mTBI).
Allergan, an AbbVie company, announced the Phase III GEMINI 1 and 2 clinical trials of AGN-190584 (pilocarpine 1.25%) ophthalmic solution for presbyopia hit their primary efficacy endpoint. AGN-190584 is an optimized formulation of pilocarpine, a cholinergic muscarinic receptor agonist. Presbyopia is otherwise known as farsightedness.
Novartis advanced NIS803 into Phase II, triggering a $25 million milestone payment to XOMA Corporation. NIS793 is an anti-TGFbeta monoclonal antibody being investigated for first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). Novartis licensed the compound from XOMA.
Finch Therapeutics presented data from the positive PRISM3 trial of CP101 for the prevention of recurrent C. difficile infection. The data was an expansion on positive topline data previously reported from the trial, a Phase II trial, demonstrating the antibiotic hit the primary efficacy endpoint.
MediWound completed enrollment of its NexoBrid Phase III pediatric clinical trial. The trial is evaluating NexoBrid compared to standard-of-care in hospitalized children with severe thermal burns of 1% to 30T of Total Body Surface Area. NexoBrid is a topically administered biological product that enzymatically removes nonviable burn tissue.
Gyroscope Therapeutics announced the first surgery using its Orbit Subretinal Delivery System (Orbit SDS) to deliver its investigational gene therapy, GT005, to a patient with geographic atrophy (GA) secondary to dry age-related macular degeneration, as part of the ongoing Phase I/II FOCUS trial. The Orbit SDS delivers a controlled volume beneath the retina.
Sanofi is partnering with Merck to test its THOR-707 compound with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in solid tumors. THOR-707 is a non-alpha IL-2 candidate that is currently being studied in Phase I trials in solid tumors. The two companies will launch a Phase II trial to evaluate the combination’s safety, pharmacokinetics and preliminary efficacy in a variety of cancers.
AbbVie presented new data that demonstrated that significantly more atopic dermatitis patients receiving Rinvoq (upadacitinib) monotherapy achieved improvement in additional measures of skin clearance and itch reduction compared to placebo. This was data from the Phase III Measure Up 1 and 2 trials.
Arcus Biosciences is teaming with AstraZeneca to study domvanalimab in combination with Imfinzi (durvalumab) in a registrational Phase III trial in unresectable Stage III non-small cell lung cancer (NSCLC). Domvanalimab is Arcus’s investigational anti-TIGIT antibody. Imfinzi is currently the only immunotherapy approved for unresectable Stage III NSCLC.
Vaccinex reported additional data from its recently completed Phase II SIGNAL study of pepinemab in Huntington’s disease. Pepinemab blocks SEMA4D and as a potential disease-modifying treatment of Huntington’s, Alzheimer’s and other neurodegenerative disorders.
Incyte announced efficacy and safety data from pooled results from two Phase III trials, TRuE-AD1 and TRuE-AD2 evaluating ruxolitinib cream in mild-to-moderate atopic dermatitis (AD). The new data reinforce that ruxolitinib showed a rapid, substantial and sustained decrease in itch and improved the extent and severity of AD.
AnHeart Therapeutics published pooled analysis of two Phase I trials of taletrectinib. The drug is a next-generation ROS1/NTRK inhibitor. It was evaluated in non-small cell lung cancer.
Zai Lab dosed the first patient in China in the POD1UM-101 trial of retifanlimab in patients with previously treated, microsatellite instability-high endometrial cancer. The drug is a checkpoint inhibitor against PD1.
Hookipa Pharma dosed the first patient with HB-202 for Human Papillomavirus 16-positive cancers as part of its ongoing HB-201 Phase I/II trial. HB-202 is a replicating arenavirus therapy based on the Pichinde Virus (PICV). They are engineered using different arenavirus backbones while expressing the same antigen, an E7/E6 fusion protein derived from HPV16.
AstraZeneca reported that in the PONENTE Phase IIIb open-label trial, Fasenra (benralizumab) eliminated the use of maintenance oral corticosteroids in OCS-dependent asthma patients. It met both co-primary endpoints, with 62% of patients achieving complete elimination of daily OCS use and 81% achieving complete elimination or were able to reduce their daily OCS dose to 5mg or less when further reduction was impossible due to adrenal insufficiency.
Polyphor AG completed recruitment in its FORTRESS Phase III trial of balixafortide in metastatic breast cancer. Balixafortide is a potent blocker of CXCR4, a key molecule involved in tumor growth and metastasis.
ChemoCentryx announced positive topline data from its AURORA Phase II trial of avacopan for chronic disabling skin disease Hidradenitis Suppurativa (HS). Avacopan is a first-in-class, orally-administered selective inhibitor of the complement C5a receptor.
Axovant Gene Therapies presented patient-level data in cohort 2 of SUNRISE-PD, showing that its AXO-Lenti-PD gene therapy had a favorable safety and tolerability profile and showed improvement in Parkinson’s disease. AXO-Lenti-PD adds three genes that help to produce dopamine into the putamen, the part of the brain impacted by the loss of dopamine in Parkinson’s disease.
Oncoceutics dosed the first patient in its Phase I trial of next-generaiton imipridone ONC206 for recurrent primary CNS neoplasms. ONC206 is part of the family of drug candidates known as imipridones.
Aligos Therapeutics dosed the first patient in its Phase Ia/b trial of ALG-000184 in hepatitis B. The drug is a small molecule class II capsid assembly modulator (CAM) that targets the virus’s capsid assembly as well as the establishment of covalently closed circular DNA (cccDNA).