Clinical Catch-Up: October 5-9

It was a moderately busy week for clinical trial news. Here’s a look.

COVID-19-Related

Karyopharm Therapeutics announced an oral presentation at the International Society for Influenza and Other Respiratory Virus Diseases Antiviral Group (ISIRV-AVG) Virtual Conference on Therapeutics for COVID-19. The presentation will include data from a Phase II trial of low dose oral Selinexor in hospitalized severe COVID-19 patients. An interim analysis suggested the trial was unlikely to hit its primary endpoint, so the trial was discontinued, but the results showed encouraging anti-viral and anti-inflammatory activity in a subset of treated patients.

ChromaDex published a new Phase II trial of hydroxychloroquine and combined metabolic cofactors supplementation (CMCS) of L-serine, Nacetyl-L-cysteine (NAC), nicotinamide riboside (NR), and L-carnitine tartrate on ambulatory COVID-19 patients. The results, which have not been peer-reviewed yet, suggest the combination significantly reduced the average complete recovery time compared with hydroxychloroquine and placebo alone.

Vir Biotechnology and GlaxoSmithKline expanded their Phase III COMET-iCE Monoclonal Antibody Efficacy Trial – Intent to Care Early study. The trial is evaluating VIR-7831 for early treatment of COVID-19 in patients who are at high risk of hospitalization. VIR-7831 is a fully human anti-SARS-CoV-2 monoclonal antibody.

ARCA biopharma received the go-ahead from the FDA to initiate a Phase IIb/III trial of AB201 for hospitalized COVID-19 patients followed by a contiguous Phase III trial based on Phase II results. AB201 is a small recombinant protein being developed for RNA virus-associated diseases, initially focusing on COVID-19. It is a potent, selective inhibitor of tissue factor (TF).

Caladrius Biosciences opened its proof-of-concept study of CLBS119 for COVID-19-induced lung damage. This 12-patient open-label trial is designed to evaluate CLBS119, which is peripheral blood-derived autologous CD34+ cells, for the lung damage caused by COVID-19 in adults.

The U.S. National Institutes of Health (NIH) is launching a clinical trial of a combination of Gilead Sciences’ antiviral drug remdesivir (Veklury) and hyperimmune intravenous immunoglobulin (hIVIG). hIVIG is a highly concentrated mixture of antibodies against SARS-CoV-2, the virus that causes COVID-19. They are culled from blood plasma donated by healthy people who have recovered from COVID-19. They are then purified and concentrated.

Four companies are collaborating to generate the hIVIG: Emergent BioSolutions of Gaithersburg, Maryland; Grifols SA of Barcelona; CSL Behring of King of Prussia, Pennsylvania; and Takeda Pharmaceuticals of Tokyo. The Emergent and Grifols hIVIG was developed with financial support from the Biomedical Advanced Research and Development Authority (BARDA). Behring and Takeda are providing their hIVIG as part of a partnership of plasma companies known as the CoVIg-19 Plasma Alliance.

The trial itself is dubbed ITAC, which stands for Inpatient Treatment with Anti-Coronavirus Immunoglobulin. The trial will enroll 500 adults 18 years or older who have been hospitalized for COVID-19 and have had symptoms for 12 days or less and do not have life-threatening organ dysfunction or organ failure. It will take place at up to 58 sites in Africa, Asia, Europe, North America and South America. Patients will receive either infusion of hIVIG and remdesivir or placebo and remdesivir.

Gilead Sciences published final results from the NIAID Phase III ACTT-1 trial of Veklury (remdesivir) in adults hospitalized with mild-moderate or severe COVID-19. The data was consistent with previous results, showing clinically meaningful improvements across multiple outcome assessments compared to placebo.

Eli Lilly and Incyte shared additional data demonstrating baricitinib in combination with Gilead’s remdesivir decreased time to recovery and improved clinical outcomes for COVID-19 patients compared to remdesivir. This was part of additional efficacy and safety data from the Adaptive COVID-19 Treatment Trial (ACTT-21) sponsored by NIAID.

Rigel Pharmaceuticals enrolled the first patients in its Phase II trial of fostamatinib in hospitalized COVID-19 patients. Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor. The drug is marketed in the U.S. as Tavalisse and in Europe for adult chronic immune thrombocytopenia (ITP).

Non-COVID-19-Related

Arcturus Therapeutics completed the first three dose escalation cohorts in its ongoing Phase I trial of ARCT-810 in healthy adults. ARCT-810 is an mRNA-based candidate for Ornithine Transcarbamylase (OTC) deficiency. The therapy uses the company’s LUNAR lipid-mediated delivery platform to deliver OTC messenger RNA to liver cells.

Amgen announced data that reinforced the long-term safety and efficacy profile of Aimovig (erenumab-aooe) in patients with episodic migraine (EM). The results are from the five-year, open-label treatment period of a Phase II trial. It demonstrated the drug helped patients achieve sustained decreases in monthly migraine days (MMD) and in use of migraine-specific medication (MSM), such as triptans.

Amgen also presented positive topline data from the Phase II CodebreaK 100 trial of sotorasib in KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC). Specifically, this was in patients who had failed a median of two previous lines of cancer therapies, including immunotherapy and/or chemotherapy. Sotorasib hit the trial’s primary endpoint, demonstrating an objective response rate (ORR) consistent with the Phase I data. Other efficacy measurements, including duration of response, were also promising, with more than 50% of responders remaining on treatment and continuing to respond as of the data cutoff date.

Amgen, along with Cytokinetics and Servier, announced topline results from their Phase III cardiovascular trial, GALACTIC-HF. The trial evaluated omecamtiv mecarbil, which significantly demonstrated improvement for heart failure patients with reduced ejection fraction (HFrEF), but did not meet the secondary endpoint of extending life expectancy.

Fulcrum Therapeutics initiated its Phase I trial with FTX-6058 for sickle cell disease. FTX-6058 is a small molecule developed to increase expression of fetal hemoglobin. The Phase I trial will be made up of four parts: A will be a single ascending dose study in up to six cohorts; B will be multiple ascending dose study in up to four cohorts dosed once daily for 14 days; C will be an open label pilot food effect study; and D will be an open label study to evaluate the potential of inducing CYP3A using midazolam.

Corbus Pharmaceuticals announced topline results from its 28-week Phase IIb trial of lenabasum in cystic fibrosis (CF). The trial did not meet the primary endpoint of a statistically significant reduction in rate of new PEx per subject per 28 weeks.

GemVax and KAEL applied for an expanded access IND for GV1001 to include additional investigational groups in Alzheimer’s. The decision was based on encouraging recent analysis of data from a Phase II trial completed last year in Korea. If granted, the company would run a second Phase IIb trial in the U.S., which is currently planned for early 2021.

PhaseBio Pharmaceuticals expanded its pivotal Phase III REVERSE-IT trial for bentracimab into Canada. Bentracimab is a novel, human monoclonal antibody fragment that has shown immediate and sustained reversal of the antiplatelet effects of Brilinta (ticagrelor).

Axovant Gene Therapies reported six-month follow-up data from the second cohort of patients who were dosed with 1.4 X 10⁷ TU of gene therapy in the SUNRISE-PD Phase II trial of AXO-Lenti-PD for Parkinson’s disease. The therapy was generally well-tolerated in all four patients who received it with no serious adverse events. Two evaluable patients in Cohort 2 showed a 21-point mean improvement in the UPDRS Part III “OFF” score, a 40% improvement from the baseline average score of 52 in these patients.

EIP Pharma announced that the Phase II AscenD-LB trial in patients with mild-to-moderate dementia with Lewy bodies (DLB) met the primary endpoint of improvement in cognition as assessed by the Neuropsychological Test Battery (NTB). In the study, patients received neflamapimod three times daily. Neflamapimod is a brain-penetrant, oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha. P38alpha is expressed in neurons under stress and disease and plays a major role in inflammation-induced synaptic toxicity.

Tyber Medical launched a clinical study with its titanium-integrated interbody fusion devices for use in the cervical and lumbar spine. The devices include titanium-integrated Polyetheretherketone (PEEK) devices that offer titanium integration for solid bone formulation between the device and surrounding tissues after spinal fusion surgery. This maximizes the potential for bone growth.

Bristol Myers Squibb reported its Phase III CheckMate -816 trial hit a primary endpoint of pathologic complete response (pCR) in resectable non-small cell lung cancer (NSCLC). Significantly more patients receiving Opdivo (nivolumab) plus chemotherapy before surgery demonstrated no evidence of cancer cells in their resected tissue compared to those treated with chemotherapy alone. Opdivo is BMS’s checkpoint inhibitor.

Pfizer and Opko Health reported their Phase III clinical trial of somatrogon met the primary endpoint compared to Genotropin (somatropin) for treating children 3 to 18 years of age with growth hormone deficiency (GHD). Somatrogon is a new molecular entity. It contains the natural sequence of growth hormone and a copy of the C-terminal peptide (CTP) from the beta chain of human chorionic hCG at the N-terminus and two copies at the C-terminus. The data from the trial demonstrated that somatrogon once a week improved the mean overall Life Interference total score after 12 weeks of treatment compared to treatment with somatropin given once a day. Key secondary endpoints also suggested an overall benefit with somatrogon compared to somatropin.

Sagimet Biosciences announced new data from its Phase II FASCINATE-1 trial of TVB-2640 for nonalcoholic steatohepatitis (NASH). The trial demonstrated significantly lower liver fat and serum biomarkers of liver injury, fibrosis and inflammation. TVB-2640 is a first-in-class, FASN inhibitor.

The German Breast Group (GBG) and Pfizer announced their Phase III PENELOPE-B trial did not meet the primary endpoint of improved invasive disease-free survival (iDFS) in women with hormnone receptor-positive (HR+), human epidermal growth factor-negative (HER2-) early breast cancer (eBC) who have residual invasive disease after completing neoadjuvant chemotherapy. The study compared one year of palbociclib plus at least five years of standard adjuvant endocrine therapy.

Jazz Pharmaceuticals announced positive topline results from the Phase III trial of Xywav (calcium, magnesium, potassium, and sodium oxybates) in adults with idiopathic hypersomnia. Patients had excessive daytime sleepiness typical of this indication. The primary endpoint was Epworth Sleepiness Scale (ESS) improvements. Xywav is approved by the FDA for cataplexy or excessive daytime sleepiness in patients seven years of age and older with narcolepsy.

Bold Therapeutics treated the first patient for the company’s Phase Ib oncology trial. It is evaluating BOLD-100 in combination with current standard-of-care, FOLFOX, for advanced gastric, pancreatic, colorectal and bile duct cancers. BOLD-100 is a first-in-class ruthenium-based therapeutic that selectively inhibits stress-induced upregulation of GRP78 and alters the unfolded protein response (UPR), mitigating resistance, survival and proliferation.