Clinical Catch-Up: August 24-28
As August wraps up, there were still clinical trial announcements, although fewer than earlier this summer. Here’s a look.
Novavax enrolled the first patients in the Phase II part of its ongoing clinical trial of NVX-CoV2373, its COVID-19 vaccine candidate. The Phase II portion expands on the age range of the Phase I part by including adults 60 to 84 years of age as about 50% of the trial population.
Humanetics Corporation and Pharmaceutics International are partnering to support a clinical trial of BIO 300 in COVID-19 patients. The study will focus on people treated for severe COVID-19, discharged from the hospital, and who continue to recuperate at home. BIO-300 is a highly selective modulator of inflammation, cell cycle arrest and DNA damage repair being developed for several indications including oncology and defense countermeasures.
Partner Therapeutics announced the first patient had been enrolled in the iLeukPulm Phase II trial of inhaled Leukine in hospitalized COVID-19 patients with acute hypoxemia. Leukine (sargramostim) is a recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF). The company also entered into a $35 million milestone-based Firm Fixed Price (FFP) deal with the Department of Defense to fund two Phase II trials of Leukine in COVID-19 patients with acute hypoxemia.
Celltrion Group received the go-ahead from the Korean Ministry of Food and Drug Safety to begin a Phase I trial of CT-P59 for COVID-19. The company has started enrolling patients with mild symptoms. CT-P59 is an antiviral antibody treatment candidate. The company launched a Phase I trial of the therapy in the UK in July.
Moderna presented more detailed data from the Phase I trial of its mRNA COVID-19 vaccine at the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP). In looking at the 100-microgram dosage of the vaccine, Moderna and NIH investigators split the Phase I trial into three age groups: 15 to 55, 56 to 70, and 71-and-older. In comparing their data to the blood of patients who recovered from COVID-19 (convalescent) and evaluating out to day 57, the 100-microgram dose met “geometric mean titer levels of 267 for the 18-55 year old cohort, 235 for the older adult cohort (ages 56-70) and 242 for the elderly cohort (ages 71+), compared to the previously published GMT of 109 in the convalescent sera.”
Adding to that, the company noted that neutralizing antibody titers and T-cell responses in both the 56-70 and 71+ age groups were consistent with the titers and responses observed in younger adults. The vaccine also stimulated Th1-biased CD4 T-cell responses in both the 56-70 and 71+ cohorts.
Novartis announced that its Phase III COMBI-I trial of its experimental checkpoint inhibitor spartalizumab in combination with Tafinlar (dabrafenib) and Mekinist (trametinib) failed to hit the primary endpoint in melanoma. Specifically, the trial did not meet the primary endpoint of investigator-assessed progression-free survival. The trial was testing the drug in combination with Tafinlar and Mekinist in untreated patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600 mutation-positive cutaneous melanoma compared to Tafinlar and Mekinist alone.
Bristol Myers Squibb announced that the Phase III IDHENTIFY trial of Idhifa (enasidenib) plus best supportive care (BSC) compared to conventional care, did not meet the primary endpoint of overall survival (OS) in relapsed or refractory acute myeloid leukemia (r/r AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. Specifically, the trial evaluated Idhifa versus conventional care regimens, which include best support care (BSC) only, azacytidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC. The patients were 60 years or older with AML refractory to or relapsed after second- or third-line AML therapy and positive for an IDH2 mutation. The primary endpoint was overall survival. Key secondary endpoints included overall response rate, event-free survival, duration of response and time to response.
Silverback Therapeutics initiated a Phase I trial of SBT6050 in adults with HER2-expressing solid tumors. SBT6050 is a specific small molecule tool-like receptor 8 (TLR8) agonist conjugated to a HER2-directed monoclonal antibody. TLR9 is highly expressed in myeloid cells that are common in human tumors.
Takeda Pharmaceutical and Ovid Therapeutics announced positive topline data from the Phase II ELEKTRA trial of soticlestat in children with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS). Soticlestat is a potent, highly selective, oral, first-in-class inhibitor of cholesterol 24-hydroxylase (CH24H). The drug hit the primary endpoint, demonstrating a 27.8% median reduction from baseline in convulsive seizure (DS) and drop seizure (LGS) compared to a 3.1% median increase in patients taking placebo during the 12-week maintenance period.
Dermavant Sciences announced positive data from two Phase III clinical trials, PSOARING 1 and 2. The trials were identical, multi-center, randomized, vehicle-controlled, double-blind, parallel studies that evaluated tapinarof cream, 1% in adults with plaque psoriasis. Tapinarof is a potential first-in-class, once-daily therapeutic aryl hydrocarbon receptor modulating agent (TAMA) topical cream. It is also being developed for atopic dermatitis. In addition to tapinarof demonstrating highly statistically significant improvement in the primary endpoint, the drug in both trials demonstrated highly statistically significant improvement in PAS175 from baseline at Week 12, which was a key secondary endpoint. Also, up to 80% of participants achieved an equal or greater than 1-grade improvement in PGA across both studies.
DURECT Corporation presented data from a Phase IIa trial of DUR-928 in alcoholic hepatitis at the Digital International Liver Congress 2020 (EASL). The drug was well tolerated at all doses tested in 19 AH patients, including 12 severe AH patients. DUR-928 epigenetically modulates the expression of multiple clusters of master genes involved in cell signaling pathways, by which it stabilizes mitochondria, reduces lipotoxicity, regulates inflammatory or stress responses, and promotes cell survival.
Natera announced a collaborative agreement with Mass General Cancer Center (MGCC) of Massachusetts General Hospital for a Phase II trial of Kisqali (ribociclib), a CDK4/6 inhibitor for the treatment of ER+ breast cancer. LEADER (part II) will randomize patients who have localized post-menopausal breast cancer with detectable ctDNA after surgery as evidence of minimal residual disease and will determine tumor molecular response after Kisqali in combination with endocrine therapy compared to endocrine therapy alone. Natera’s Signatera test will be leveraged for patient enrollment eligibility.
Jazz Pharmaceuticals presented data at the Virtual SLEEP 2020, the 34th annual meeting of the Associated Professional Sleep Societies (APSS). Three posters presented data from the Phase III withdrawal study of JZP-258 in adults with narcolepsy with cataplexy.