Navitor Pharmaceuticals announced the initiation of a Phase I clinical study with its lead pipeline candidate, NV-5138, for treatment-resistant depression (TRD). NV-5138 is a novel small molecule that directly activates mTORC1, a master cellular regulator that has recently been shown to be a central signaling pathway required for the efficacy of several rapid acting antidepressants. NV-5138 is initially being evaluated in TRD but may offer future potential for the treatment in the broader disease category of major depressive disorder (MDD). The Phase I, multicenter, two-part, double-blind, placebo-controlled study will evaluate the safety, tolerability and pharmacokinetics of NV-5138 in up to 88 subjects, including healthy volunteers and patients diagnosed with TRD. In Part A, the single-ascending-dose portion of the study, up to 48 healthy volunteers will be randomly assigned to double-blind treatment in six dosage-level cohorts. Within each cohort, six subjects will be randomized to receive NV-5138 and two subjects will be randomized to receive placebo. In Part B of the study, approximately 40 subjects diagnosed with TRD will be randomly assigned to double-blind treatment at a single dosage level that will be established based on data from Part A of the study.
Amgen announced results from a Phase III study evaluating the efficacy and safety of biosimilar candidate ABP 710 compared with REMICADE (infliximab) in patients with moderate-to-severe rheumatoid arthritis. The results confirm non-inferiority compared to infliximab but could not rule out superiority based on its primary efficacy endpoint, which compared the response difference measured by 20 percent or greater improvement at week 22. Key secondary endpoints included ACR50, ACR70 and Disease Activity Score 28-joint count C reactive protein (DAS28-CRP).The primary endpoint of ACR20 had a prespecified equivalence margin of +/- 15 percent, and the observed upper end of the confidence interval was 15.96 percent. The Phase III study was a randomized, double-blind trial. There were 558 patients enrolled and randomized (1:1) to receive either ABP 710 or infliximab at a dose of 3 mg/kg administered as an infusion on day 1, at weeks 2 and 6, and every 8 weeks thereafter. Among them, 279 patients were randomized to the ABP 710 group and 279 patients were randomized to the infliximab group. The primary endpoint was assessment of ACR20 at week 22. Key secondary endpoints included ACR50, ACR70 and the DAS28-CRP.
Global Blood Therapeutics announced the completion of a planned review of Part A of the Phase III HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study, which is evaluating voxelotor for the treatment of sickle cell disease (SCD). On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1500 mg and 900 mg doses after 12 weeks of treatment versus placebo. The HOPE Study is a randomized, double-blind, placebo-controlled, multi-national study that enrolled patients age 12 and older with SCD who had had at least one episode of VOC in the previous year. The study was originally designed in two parts: Part A compared voxelotor administered at doses of 900 or 1500 mg per day versus placebo in 154 patients treated for at least 12 weeks, and Part B planned to enroll 250 patients randomized to placebo or a dose of voxelotor selected from Part A. The primary efficacy endpoint is the proportion of patients who achieve a greater than 1 g/dL increase in hemoglobin at 24 weeks of treatment compared with baseline. Key secondary efficacy endpoints evaluated in Part A were the effect of voxelotor on SCD symptom exacerbation as measured by the PRO instrument, overall SCD symptoms as measured by the PRO instrument, and traditionally defined VOCs. The study found 58 percent of patients taking the 1500 mg dose (p<0.0001) and 38 percent of patients taking the 900 mg dose (p=0.0021) achieved a greater than 1 g/dL increase in hemoglobin at 12 weeks versus 9 percent of patients taking placebo. This compares favorably to the hemoglobin increase assumption agreed to with the U.S. Food and Drug Administration (FDA) in the HOPE Study protocol of a 35 percent response.
BioAtla announced the treatment of the first patient in its clinical trial BA3021-001 for BioAtla’s BA3021, a novel conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC). This is a multi-center, open-label, Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of BA3021 in patients with advanced solid tumors including non-small cell lung cancer (NSCLC), triple negative breast cancer and soft tissue sarcoma. The CAB-ROR2-ADC BA3021 is designed to maximize efficacy on ROR2 expressing tumors while minimizing toxicity, leading to better clinical outcomes. The ROR2 transmembrane protein tyrosine kinase is an onco-fetal protein that acts as a non-canonical Wnt 5A receptor. ROR2 is found to be highly expressed during embryonic development and in several important cancer types, and the level of expression in tumors is tightly correlated with patient prognosis.