Clinical Catch-Up: October 12-16
It was another busy week for both COVID-19-related clinical trial news as well as trial updates for other indications. Here’s a look.
AstraZeneca reported the long-acting antibody (LAAB) combination, AZD7442, will advanced into two Phase III clinical trials. The trials will evaluate more than 6,000 participants in and outside the U.S. The LAABs have been designed with the company’s proprietary half-life extension technology. The intention is to increase the durability of the antibodies for six to 12 months after a single dose. AZD7442 is a cocktail of two LAABs, which decreases the risk of the SARS-CoV-2 virus developing resistance to the antibodies.
AZD7442 is made up of two LAABs derived from convalescent patients who recovered from COVID-19. The LAAB technology was discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020. They were optimized by AstraZeneca with half-life extension and reduced Fc receptor binding. The reduced Fc receptor binding is to minimize the risk of antibody-dependent disease enhancement, which sometimes happens where antibodies against a virus promote, instead of inhibit, infection and disease.
One of the AZD7442 trials will evaluate the safety and efficacy of the antibody cocktail in preventing infections for up to 12 months in about 5,000 participants. A second trial will study about 1,100 patients who have been exposed to COVID-19 to determine if it can prevent the disease post-exposure. The company also is planning additional trials in about 4,000 patients for treatment of COVID-19.
Johnson & Johnson paused its clinical trial of its COVID-19 vaccine due to “an unexplained illness in a study participant.” The company began its Phase III trial of JNJ-78436735 on September 23. J&J did not disclose much information about the unexplained illness, stating, “We must respect this participant’s privacy. We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information.”
The company also emphasized that adverse events are part of most clinical trials and that this is a “study pause” instead of a “clinical hold,” which is a formal regulatory action. A “clinical hold” can last much longer than a “study pause.”
A new clinical trial by the World Health Organization (WHO) reports that Gilead Sciences’ Veklury (remdesivir) does not have any particular effect on a patient’s survival. WHO’s SOLIDARITY clinical trial evaluated remdesivir and three other drugs in 11,266 hospitalized COVID-19 patients and found that none of the drugs “substantially affected mortality” or decreased the need to ventilate patients, reported the Financial Times.
“These remdesivir, hydroxychloroquine, lopinavir and interferon regimens appeared to have little effect on in-hospital mortality,” the study stated. The WHO trial also demonstrated that the drugs did not affect hospital stays, which seems in contradiction to previous studies. However, WHO scientists said that was not the focus of the trial, which was designed to evaluate the impact on in-hospital mortality. The study has not yet been peer-reviewed.
Caladrius Biosciences opened its proof-of-concept study of CLBS119 for COVID-19-induced lung damage. CLBS119 is made up of peripheral blood-derived autologous CD34+ cells. The study will evaluate 12 patients.
Mesoblast Limited’s Phase III trial of remestemcel-L with maximal care in ventilator-dependent patients with ARDS from COVID-19 surpassed 50% enrollment. The primary endpoint is reduction in 30-day mortality relative to maximal care. Remestemcel-L is made up of culture-expanded mesenchymal stem cells derived from the bone marrow of an unrelated donor.
Pfizer announced they had received approval from the U.S. Food and Drug Administration (FDA) to enroll children as young as 12 years of age in its COVID-19 vaccine trial. The goal is to determine the safety and efficacy of the vaccine in adolescents. To date, the Phase II/III trial has enrolled 37,864 people and of them, 31,062 have received their second vaccination. It has 120 sites in four countries, with 39 in the U.S.
PharmaMar announced that its APLICOV-PC1,2 trail of Aplidin (plitidepsin) for hospitalized adults with COVID-19 had hit both primary safety and secondary efficacy endpoints. In the study, there was a substantial decrease of the viral load in patients between days 4 and 7 and 80.7% were discharged on or before the 15th day of hospitalizations, and 38.2% before the eighth day. Aplidin is isolated from the sea squirt (Aplidium albicans) and has demonstrated anti-myeloma activity. It binds to the specific protein product of the eEF1A2 gene on tumor cells.
Astellas Pharma and Seagen announced positive topline results from the second cohort in its Phase II trial, EV-201. The cohort is evaluating the antibody-drug conjugate (ADC) Padcev (enfortuma vedotin-ejfv) in locally advanced or metastatic urothelial cancer patients who have been previously treated with a checkpoint inhibitor and have not received platinum-containing chemotherapy and are ineligible for cisplatin. Data demonstrated a 52% objective response rate (ORR). Padcev is a first-in-class ADC directed against Nectin-4, which is a protein highly expressed in bladder cancer.
Regeneron Pharmaceuticals and Sanofi reported that a Phase III trial of Dupixent (dupilumab) hit its primary and all key secondary endpoints in children aged 6 to 11 years with uncontrolled moderate-to-severe asthma. The primary endpoint assessed the annualized rate of severe asthma attacks in two primary pre-specified populations: patients with baseline blood EOS greater than or equal to 300 cells/microliter and patients with markers of type 2 inflammation. In those two patient groups, the ones who added Dupixent to standard of care had fewer severe asthma attacks and demonstrated improved lung function.
Voyager Therapeutics indicated that after its IND submission for VY-HTT01 in September 2020, the FDA had notified them that the IND was placed on clinical hold pending the resolution of certain chemistry, manufacturing and controls (CMC) issues. VY-HTT01 is being developed to treat Huntington’s disease.
Evelo Biosciences dosed the first patients in its Phase II trial of EDP1815 for mild to moderate psoriasis. EDP1815 is an oral biologic for inflammatory diseases including psoriasis, atopic dermatitis, and COVID-19. It is a strain of Prevotella histicola. It also announced it had completed enrollment of 24 patients in the Phase Ib trial cohort of the drug in mild to moderate atopic dermatitis.
Cyclerion Therapeutics announced results from its Phase I translational pharmacology study of IW-6463. IW-6463 is the first sGC stimulator in development for central nervous system disorders. In the study, the daily oral drug demonstrated desired CNS exposure, blood-brain-barrier penetration and target engagement. It also showed statistically significant improvements in various markers associated with age-related cognitive decline and neurodegenerative diseases. The company also announced topline data from its STRONG-SCD study of olinciguat in sickle cell disease. It was generally well tolerated but did not demonstrate adequate activity to support more internal clinical development.
Vertex Pharmaceuticals announced that after early data on its Phase II trial of VX-814 in Alpha-1 antitrypsin deficiency (AATD), it is halting the trial and ending development of the drug. The trial was in about 50 patients and was to evaluate the safety and pharmacokinetics of VX-814 and its ability to increase functional levels of alpha-1 antitrypsin over 28 days. Patients demonstrated elevated liver enzymes, AST/ALT, and in four patients, across different doses, the elevated liver enzymes were eight times greater than the upper limit of normal. To date the elevated liver enzymes have either resolved or are resolving. The company decided that based on the data, it would not be feasible to safely reach exposure levels.
Amylyx Pharmaceuticals published overall survival analysis from the CENTAUR trial evaluating AMX0035 in amyotrophic lateral sclerosis (ALS). The analysis followed each trial participant for up to three years from the start of the trial and found participants randomized to AMX0035 at baseline had a 44% lower risk of death compared to the group who originally received placebo over the duration of follow-up. The drug is a neuroprotective therapy designed to decrease the death and dysfunction of motor neurons through targeting of mitochondrial and endoplasmic reticulum related cell death pathways.
Galapagos NV and Servier reported their ROCELLA Phase II clinical trial of GLPG1972/S201086 failed to meet its primary endpoint in osteoarthritis knee repair. The focus of the trial was to demonstrate efficacy of at least one dose of GLPG1972/S201086 compared to placebo after 52 weeks in reducing cartilage loss of the central medial tibiofemoral compartment of the target knee via quantitative MRI. The trail failed to do so, with the change from baseline to week 52 in cartilage thickness being -0.116 for the placebo group and -0.068, -0.097 and -0.085 for the low, medium and high dose groups, respectively. There was also no statistically significant difference observed compared to placebo on any of the secondary endpoints, including clinical outcomes. The drug’s mechanism of action targets a cartilage degrading enzyme called ADAMTS-5.
Orion Biotechnology Canada reported results from their Phase I trial of OB-002H for prevention of HIV. The drug is a highly potent chemokine analog of CCL5, an HIV co-receptor. The study included open-label single-dose (vaginal and rectal) and multi-dose product (vaginal) administration of OB-002H gel. The product was well tolerated, and adverse events were mild or moderate.