Clinical Catch-Up: April 20-24

Clinical Trial Technology

Despite the domination of the news cycle by the COVID-19 pandemic, quite a number of biopharma companies reported on non-COVID-19 clinical trials last week, although there remains plenty of ongoing trial news related to the pandemic. Here’s a look.


Mesoblast Limited announced that in a study of COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS), there was 83% survival with two intravenous infusions of the company’s experimental allogeneic mesenchymal stem cell candidate Ryoncil (remestemcel-L).

Ryoncil is currently under priority review by the U.S. Food and Drug Administration (FDA) for steroid-refractory acute graft versus host disease (acute GVHD). It is also under development for other rare diseases.

In the study, nine out of 12 patients, or 75%, successfully came off ventilators within 10 days, and the 83% figure refers to the patients coming off the ventilator in the first five days. Seven of the patients have been discharged from the hospital. All the patients had received other experimental therapies before receiving remestemcel-L. They were treated under an emergency Investigational New Drug (IND) application or via expanded access protocol at New York City’s Mt. Sinai hospital.

WHO added three more vaccine COVID-19 clinical trials to its list, now totaling six. In China they are: Cansino Biological/Beijing Institute of Biotechnology; Sinovac; Beijing Institute of Biological Products/Wuhan Institute of Biological Products. In the U.S. they are: Moderna/NIAID. In the UK, there is a Phase I/II trial by the University of Oxford. WHO also identified 77 other vaccines that are in preclinical stages of research.

Novartis is launching a Phase III clinical trial of about 440 patients with COVID-19 to evaluate the effectiveness of hydroxychloroquine. The drug supply will be provided by Novartis’ Sandoz division. It will be run at more than a dozen sites in the U.S.

aTyr Pharmas IND for a Phase II trial of ATYR1923 in COVID-19 patients with severe respiratory complications was given the go-ahead. ATYR1923 in preclinical studies downregulated T-cell responses, dampening the inflammatory cytokine and chemokine signaling implicated in severe COVID-19. It will look at 30 confirmed COVID-19 patients at up to 10 U.S. sites.

Vaxart announced positive preclinical results from its oral COVID-19 vaccine candidate. It is based on VAAST, its oral vaccine platform. It expects to initiate a Phase I clinical trial in the second half of 2020.

Nascent Biotech has initiated tests to assess the possibility that its lead asset, the monoclonal antibody Pritumumab (PTB), could be used to treat COVID-19. The antibody recognizes the cell-surface vimentin, which is implicated in the entry of SARS-CoV-2 into the cells it infects.

China’s clinical trial of HIV drug Kaletra, marketed by AbbVie, and influenza drug Arbidol showed that they have no effect on mild to moderately severe COVID-19. It was a small trial of 86 patients, 34 receiving Kaletra (lopinavir/ritonavir) and 35 receiving Arbidol (umifenovir), while 17 patients received only supportive and oxygen if needed. Arbidol is a drug manufactured in Russia by Pharmstandard.

A retrospective study of 368 patient records from Veterans Health Administration showed that the use of hydroxychloroquine with or without azithromycin had no effect on COV ID-19. In fact, there was not only no overall benefit, there were more deaths among patients receiving hydroxychloroquine alone.

BioNTech and Pfizer received the go-ahead from German regulatory authorities to initiate the Phase I/II clinical trial of BioNTech’s BNT162 vaccine program to prevent COVID-19. It is the first trial of a COVID-19 vaccine candidate to start in Germany. It is part of a global development program. The companies will also run trials for the vaccine in the U.S. once they receive approval from the FDA.

Two companies out of Italy, Advent-IRBM and Takis Biotechnology, announced they are advancing their vaccine work in conjunction with the Jenner Institute in the UK, and hope to have it into human clinical trials in September 2020. Advent-IRBM developed five potential candidates, all based on human DNA, and is currently conducting animal trials to determine the best candidates.

On March 16, Moderna and the National Institute of Allergy and infectious Disease (NIAID) began dosing patients with mRNA-1273, its vaccine candidate against COVID-19. The second round of dosing in healthy Seattle volunteers began April 23. The Phase I trial is evaluating three doses, 25, 100 and 250 µg administered on a two-dose schedule given 28 days apart. A total of 45 healthy adults are enrolled in the study. They will be followed through 12 months after the second vaccination.

University of Oxford has dosed the first patient in its European Phase I trial of a vaccine. It expects to recruit more than 1,000 participants and finish in May 2021. The initial results will be available in the next six months. The vaccine is based on a weakened adenovirus, genetically modified to harmlessly produce the Spike protein from SARS-CoV-2.

ORYZON Genomics received approval from the Spanish Drug Agency (AEMPS) to run a Phase II trial with vafidemstat in severe COVID-19 patients. The ESCAPE study is a Phase II trial to assess the drug in combination to standard of care to prevent progression to Acute Respiratory Distress Syndrome (ARDS). It will initially have 20 patients in each arm of the trial. Vafidemstat is an oral, CNS optimized LSD1 inhibitor.


Bristol Myers Squibb and Exelixis announced that CheckMate-9ER, a Phase III trial of Opdivo (nivolumab) in combination with Cabometyx (cabozantinib) compared to sunitinib in previously untreated advanced or metastatic renal cell carcinoma (RCC), met its primary endpoint of progression-free survival (PFS), as well as secondary endpoint of overall survival (OS) and objective response rate (ORR).

Precigen plans to initiate a Phase I/II trial of PRGN-2009 in HPV-positive solid tumors. PRGN-2009 is a first-in-class, off-the-shelf (OTS) investigational immunotherapy leverage the company’s AdenoVerse platform designed to activate the immune system to recognize and target HPV+ solid tumors.

SCYNEXIS announced positive topline data from its second pivotal Phase III VANISH-306 trial of oral ibrexafungerp for vulvovaginal candidiasis (vaginal yeast infection). The drug achieved superiority over placebo with a high degree of statistical significance on key study endpoints. The drug is an investigational antifungal agent and the first of a novel class of structurally distinct glucan synthase inhibitors, the “fungerps.”

Cara Therapeutics and Vifor Fresenius Medical Care Renal Pharma (VFMCRP) announced positive topline data from Cara’s KALM-2 Phase III trial. The study evaluated Korsuva (CR845/difelikafalin) injection in hemodialysis patients with pruritus (severe itching) from moderate-to-severe chronic kidney disease (CKD-aP). CKD-aP, which is stubborn, severe systemic itching, occurs in at least 40% of kidney dialysis patients. It has also been reported in patients with stage III-V chronic kidney disease (CKD) who are not on dialysis.

AFYX Therapeutics’ Phase IIb clinical trial of its Rivelin Clobetasol patch met the primary and multiple secondary endpoints for patients with oral lichen planus (OLP). OLP is a painful inflammatory disease marked by lesions or ulcers inside the mouth. Rivelin-CLO is the first biodegradable oral adhesive patch designed for local delivery of clobetasol to treat symptomatic OLP lesions.

Catalyst Biosciences completed dosing and the 30-day follow-up period for its Phase IIb trial of SQ dalcinonacog alfa (DalcA). The trial was designed to evaluate the ability of DalcA to maintain steady state protective FIX levels to about 12% in six individuals with severe hemophilia B.

Hookipa Pharma published the results from its Phase I trial of its VaxWave-based prophylactic Cytomegalovirus (CMV) vaccine candidate HB-101, which is now in Phase II trials. The data was published in The Journal of Infectious Diseases. The vaccine was well tolerated and induced CMV-specific poly-functional CD8 T-cell and neutralizing antibody responses in almost all subjects.

WindMIL Therapeutics began enrollment in the combination therapy portion of its Phase IIa trial of MILs in patients with locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC) who are refractory to, or have relapsed on, an anti-PD-1-containing regimen. In this portion of the trial, MILs will be dosed in combination with Bristol Myers Squibb’s Opdivo (nivolumab), a PD-1 checkpoint inhibitor.

Applied Therapeutics announced new data and scientific presentations from the pivotal Phase II ACTION-Galactosemia trial. The trial evaluated AT-007, a CNS penetrant Aldose Reductase Inhibitor (ARI) in healthy volunteers. The key biomarker outcome was reduction in galactitol, an aberrant toxic metabolite of galactose.

REGENXBIO released additional long-term data from its ongoing Phase I/IIa trial of RGX-314 for wet age-related macular degeneration (wet AMD). RGX-314 is made up of the NAV AAV8 vector encoding an antibody fragment designed to inhibit VEGF, thus changing the pathway for formation of new leaky blood vessels that lead to retinal fluid accumulation and vision loss.

Myovant announced that SPIRIT 2, the first of two Phase III trials of once-daily relugolix combination therapy in women with pain associated with endometriosis met the co-primary efficacy endpoints as well as six key secondary endpoints. It achieved 100% ovulation inhibition in 67 healthy women, with no women ovulating during the 84-day treatment period. Also, 100% resumed ovulation or menses after discontinuation of treatment with an average time to ovulation of 23.5 days.

Cue Biopharma and Merck & Co. signed a collaboration deal to evaluate CUE-101 in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) as first-line treatment for HPV+ recurrent/metastatic head and neck cancer. CUE-101 is a first-in-class biologic, a Fc-fusion biologic that incorporates peptide-MHC molecules with rationally engineered IL-2 molecules. They will run a Phase I trial, KEYNOTE-A78, in parallel with the ongoing Phase I monotherapy trial of CUE-101 post first-line treatment.

Sanofi’s BTK inhibitor, SAR442168, hit the primary and secondary endpoints in a Phase IIb trial in relapsing multiple sclerosis (MS). The drug significant decreased disease activity associated with MS.

Rafael Pharmaceuticals announced the Central Drugs Standard Control Organization (CDSCO), India’s regulatory body, had granted approval for opening sites in India for its Phase III trial of devimistat in relapsed or refractory acute myeloid leukemia (r/r AML). It also received approval for opening sites in Canada by Health Canada. Devimistat is a first-in-class compound that targets the mitochondrial tricarboxylic acid (TCA) cycle.

Avenue Therapeutics presented two e-posters from its Phase III program of IV tramadol in 370 patients after abdominoplasty surgery. They were originally to be presented at the Annual Regional Anesthesiology and Acute Pain Medicine Meeting, which was canceled. They are available as an e-poster.

AstraZeneca and Merck & Co. released more positive data from the Phase III PROfound trial of Lynparza (olaparib) in metastatic castration-resistant prostate cancer (mCRPC). Specifically, in patients who have a homologous recombination repair gene mutation (HRRm) and have progressed despite previous treatment with new hormonal agent (NHA) treatments such as enzalutamide and abiraterone. Lynparza is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells and tumors with a deficiency in homologous combination repair, such as mutations in BRCA1 and 2.

Anavex Life Sciences published data outlining results from the Phase IIa trial of blarcamesine (ANAVEX2-73) in Alzheimer’s disease. The study highlights the relevance of phenotypic and genotypic precision medicine analyses of Whole Exome Sequencing (WES) and gene expression (RNAseq) data in drug development. Blarcamesine is an oral therapy that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors.

Incyte announced data from the Phase III REACH2 trial had been published. The trial evaluated Jakafi (ruxolitinib) in steroid-refractory acute graft-versus-host disease (GVHD) compared to best available therapy. The trial met its primary endpoint, showing a significantly greater overall response rate (ORR) versus BAT (62% versus 39%, respectively).

TG Therapeutics published results from the Phase II trial of ublituximab, the company’s glylcoengineered, anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis (RMS).


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