Clinical Catch-Up: March 29-April 2
It was a busy week for clinical trial news. Here’s a look.
COVID-19-Related
NeuroRx announced that Zyesami (aviptadil) met the primary endpoint of its Phase IIb/III trial, showing a meaningful survival benefit in critical COVID-19. They also indicated plans to initiate a trial of inhaled Zyesami for patients with moderate and severe COVID-19, and the drug was included in the I-SPY clinical trial platform for COVID-19 respiratory failure.
The Cancer Research Institute (CRI) and RevImmune dosed the first patient in a new Phase II trial of interleukin-7 (IL-7) in cancer patients with COVID-19. COVID-19 patients have low T-cell levels and exhausted T-cells, and the therapy is believed to augment the cellular immune response.
CytoDyn released additional data on its clinical trial of Vyrologix (leronlimab-PRO 140) in severe-to-critically ill patients with COVID-19. The drug is a CCR5 antagonist. The data found that was leronlimab was added to standard of care, leronlimab decreased mortality at 14 days by 82%.
Pfizer and BioNTech announced positive topline results of a Phase III trial in adolescents ages 12-15 for their COVID-19 vaccine. The vaccine, BNT162b2 demonstrated 100% efficacy and robust antibody responses, and was well tolerated.
Kamada announced topline data from its Phase I/II trial of its anti-SARS-CoV-2 plasma-derived hyperimmune globulin (IgG) treatment for COVID-19. It demonstrated a favorable safety profile. Of the 12 patients who received the treatment, 11 recovered, seven were discharged from the hospital at or before day 5 post-treatment, and the four remaining were discharged by day nine. One patient died on day 37 post-treatment from complications to COVID-19.
Emergent BioSolutions offered an update on its Phase III trial of SARS-CoV-2 Immune Globulin Intravenous (Human) (COVID-HIG) to treat hospitalized patients with COVID-19. Unfortunately, the ITAC trial showed that the addition of the treatment to Gilead Sciences’ remdesivir, did not provide clinical benefit compared to standard of care plus placebo in hospitalized adult COVID-19 patients with symptoms for less than 12 days. No safety issues were raised.
Pfizer and BioNTech’s current Phase III trial of the Pfizer-BioNTech COVID-19 vaccine has confirmed that protection remains high for at least six months after the second dose. In a statement, the companies reported the vaccine, BNT162b2, was 91.3% effective against the disease, measured seven days through up to six months after the second dose. More importantly, it was 100% effective against severe disease as defined by the U.S. Centers for Disease Control and Prevention (CDC) and 95.3% effective against severe COVID-19 as defined by the U.S. Food and Drug Administration (FDA).
Non-COVID-19-Related
Orphazyme announced its Phase II/III clinical trial of arimoclomal for inclusion body myositis (IBM) failed to hit both its primary and secondary endpoints. Inclusion body myositis (IBM) is a progressively debilitating muscle-wasting disease, marked by an accumulation of protein aggregates and atrophy of muscle cells. This leads to weakness and eventually to severe disability. There are currently no approved treatments.
Arimoclomol is designed to amplify the production of Heat Shock Proteins (HSPs). HSPs can rescue defective misfolded proteins, clear protein aggregates, and improve lysosome function.
uniQure announced findings from a comprehensive investigation into a case of hepatocellular carcinoma (HCC) diagnosed in one patient in the HOPE-B pivotal trial of etranacogene dezaparvovec—the conclusion was it was highly unlikely the HCC was caused by the gene therapy. Etranacogene dezaparvovec is being evaluated for Hepatitis B. The therapy consists of an AAV5 viral vector carrying a gene cassette with the Padua variant of Factor IX.
ORYZON Genomics enrolled the first patient in the PORTICO Phase IIb trial of vafidemstat in Borderline Personality Disorder (BPD). Vafidemstat is an oral, CNS optimized LSD1 inhibitor.
Adagene announced interim dose-escalation data up to 0.3 mg/kg in its ongoing Phase I trial in Australia of ADG116 in patients with advanced/metastatic solid tumors. ADG116 is a fully human, anti-CTLA-4 monoclonal antibody that targets a unique conserved epitope of CTLA-4.
Biohaven Pharmaceutical enrolled the first patient in a Phase II/III trial of oral zavegepant for the prevention of migraine. The drug is a third generation, CGRP receptor antagonist.
Hutchison China MediTech Limited initiated two international Phase I studies of HMPL-306, one for advanced solid tumors and the other in hematological malignancies. The drug is a novel selective small molecule dual inhibitor of isocitrate dehydrogenase 1 and 2 mutations.
Rafael Pharmaceuticals crossed the enrollment of 150 patients in its Phase III trial of devimistat in r/r acute myeloid leukemia (AML). The drug is being tested in combination with high dose cytarabine and mitoxantrone compared to high dose cytarabine and mitoxantrone alone in older patients. Devimistat is a first-in-class compound that targets the mitochondrial tricarboxylic acid (TCA) cycle.
Flexion Therapeutics treated the first patient in its Phase Ib trial of FX301 in post-operative pain. FX301 is a locally administered NaV1.7 inhibitor known as funapide. It is formulated for extended release in a thermosensitive hydrogel.
Equillium announced favorable topline data from the Type A group of the EQUALISE trial of itolizumab in systemic lupus erythematosus. Itolizumab is a monoclonal antibody that selectively targets the CD6-ALCAM pathway.
Acceleron Pharma published results of the PULSAR Phase II trial of sotatercept in pulmonary arterial hypertension (PAH). The data showed the drug was well-tolerated and the trial hit the primary endpoint of statistically significant reduction in pulmonary vascular resistance at week 24 versus placebo. The drug is a reverse-remodeling agent designed to be a selective ligand trap for members of the TGF-beta superfamily to rebalance BMPR-II signaling.
Altimmune reported data from its Phase Ib trial of its NasoShield intranasal anthrax vaccine candidate. The data showed that serum binding antibody responses to the protective antigen of Bacillus anthracis were significantly greater than in the placebo arm and antibody responses blocking anthrax toxin were blunted compared to protective antigen antibody responses and were low compared to previous trials conducted with BioThrax, the only approved anthrax vaccine.
SpringWorks Therapeutics dosed the first patient in its Phase Ib trial of nirogacestat with Janssen’s teclistamab in patients with relapsed or refractory multiple myeloma. Nirogacestat is SpringWorks’ investigational gamma secretase inhibitor. Teclistamab is Janssen Research & Development’s investigational bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3.
Celon Pharma completed its Phase I trial of CLP’280 for diabetes and diabetic neuropathy. The drug is a second-generation GPR40 agonist. The trial hit its primary endpoint, with no adverse safety signals.
AzurRx BioPharma presented topline results from its Phase IIb OPTION 2 trial of MS1819 in cystic fibrosis patients with exocrine pancreatic insufficiency. The data was mixed, demonstrating safety and was well tolerated, but it did not consistently meet the primary endpoint. The drug is a recombinant lipase enzyme supplied as an oral non-systemic biologic capsule derived from the Yarrowia lipolytica yeast lipase.
BioXcel Therapeutics announced topline results from its Phase Ib/II proof-of-concept RELEASE study of BXCL501 for opioid withdrawal symptoms. BXCL501 is the company’s orally dissolving thin film formulation of dexmedetomidine. The study hit its primary safety endpoint, with numerical improvements in retention rates, which were not statistically significant.