Clinical Catch-Up: December 21-25

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Even with the holidays among us, there were a number of clinical trial announcements. Here’s a look.

COVID-19-Related

Vir Biotechnology and GlaxoSmithKline dosed the first patient in a new sub-trial of a Phase III study of monoclonal antibody VIR-7831 for hospitalized adults with COVID-19.

RedHill Biopharmas Phase II/III trial of opaganib in severe COVID-19 pneumonia received a second unanimous recommendation to continue by a second IDSMB safety review. The drug, Yeliva (opaganib) is a first-in-class, oral spingosine kinase-2 (SK2) selective inhibitor with triple-action effect on the pathophysiological processes linked to COVID-19.

BioCryst Pharmaceuticals announced that data from part 1 of its trial of galidesivir demonstrated the drug was safe and generally well tolerated in patients with COVID-19. Galidesivir is a broad-spectrum antiviral, an adenosine nucleoside analog that blocks viral RNA polymerase.

CureVac and the University Medical Center of Mainz launched a Phase III trial of CVnCoV, their COVID-19 vaccine candidate, in healthcare workers. The study will evaluate the safety and immunogenicity of the vaccine in a two-dose schedule of 12 micrograms.

CytoDyn announced a treating physician received authorization from the FDA to administer leronlimab for a COVID-19 patient under emergency eIND. Vyrologix (leronlimab) recently completed a Phase III registrational trial and the company is waiting for the data to be unblinded. The drug is a humanized IgG4 monoclonal antibody that blocks CCR5 and is being developed for COVID-19, HIV and metastatic triple-negative breast cancer.

Non-COVID-19-Related

Genentech, a Roche company, announced positive topline data from two identical Phase III trials of faricimab in diabetic macular edema (DME). Both studies, YOSEMITE and RHINE, hit their primary endpoint, demonstrating that faricimab dosed every eight weeks and at personalized dosing intervals of up to 16 weeks, was non-inferior compared to Regeneron’s Eyelea (aflibercept) given every eight weeks.

Faricimab is a bispecific antibody designed specifically for the eye. The molecule targets two pathways that cause a number of retinal diseases. The pathways are angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Both pathways can cause vision loss by destabilizing blood vessels, causing new leaky blood vessels to form and creating inflammation. Faricimab independently blocks both pathways, stabilizing blood vessels.

Exelixis’ COSMIC-311 Phase III trial of Cabometyx (cabozantinib) in radioiodine-refractory differentiated thyroid cancer patients who have progressed after up to two previous VEGFR-targeted therapies met the co-primary endpoint of significant improvement in progression-free survival (PFS). It reduced the risk of disease progression or death by 78%.

Azura Ophthalmics announced topline data from its Phase III ECLIPTIC trial of AZR-MD-001 for treatment of contact lens discomfort. The trial showed statistically significant improvements in multiple measures of Meibomian gland secretion and patients’ ability to wear contact lenses as desired. AZR-MD-001’s active ingredient is selenium disulfide. The drug is a topical ointment applied to the lower lid to address the build-up and shedding of proteins at the opening of the Meibomian gland.

Sirnaomics announced positive results from its Phase IIa trial of STP705 for squamous cell skin cancer. STP705 is a small interfering RNA (siRNA) therapy that leverages a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to knock down both TGF-beta1 and COX-2 gene expression.

MAP Pharmaceuticals patient enrollment in the ongoing GA Depot Phase III trial for relapsing forms of multiple sclerosis (RMS) passed the 60% mark. GA Depot is a long-acting injection of the approved Glatiramer Acetate products (Copaxone and its generic formulations). It is designed to be dosed as an intramuscular injection once every four weeks.

Mustang Bio initiated its Phase I trial of MB-101 to patients with leptomeningeal brain tumors, such as glioblastoma, ependymoma or medulloblastoma with City of Hope. The drug is an autologous IL13Ralpha2-CAR-T cell product.

Taysha Gene Therapies announced that Queen’s University in Ontario, Canada, received Clinical Trial Application (CTA) approval from Health Canada for its Phase I/II trial of TSHA-101 for infantile GM2 gangliosidosis. TSHA-101 is an investigational gene therapy designed to deliver the HEXA and HEXB genes driven by a single promoter within the same AAV9 construct, dubbed a bicistronic vector. GM2 gangliosidosis is a rare and fatal monogenic lysosomal storage disorder and a family of neurodegenerative genetic diseases that includes Tay-Sachs and Sandhoff diseases.

aTyr Pharma completed target enrollment in its Phase Ib/IIa trial of ATYR1923 in pulmonary sarcoidosis, a form of interstitial lung disease. ATYR1923 is a fusion protein made up of the immuno-modulatory domain of histidyl tRNA synthetase fused to the FC region of a human antibody. It is a selective modulator of neuropilin-2 that downregulates the innate and adaptive immune response in inflammatory diseases.

Transgene and BioInvent International received regulatory approval in Belgium for a Phase I/IIa trial of oncolytic Vaccinia virus BT-001. BT-001 is a best-in-class oncolytic Vaccinia virus generated using Transgene’s Invir.IO platform and its large-capacity VVCop TK”RR” oncolytic virus, engineered to encode both a Treg-depleting human recombinant anti-CTLA4 antibody generated by BioInvent’s n-CoDeR/F.I.R.S.T. platforms and the human GM-CSF cytokine.

OSE Immunotherapeutics enrolled the first patient in its Phase II trial of OSE-127/S95011 for severe active ulcerative colitis. The drug is an anti-IL-7 receptor antagonist. The study population is patients with moderate to severe ulcerative colitis who have failed or are intolerant to immunosuppressors, anti-tumor necrosis factor, anti-integrin, ustekinumab and/or corticosteroids.

ChemoCentryx and Vifor Fresenius Medical Care Renal Pharma (VFMCRP) announced topline data from the ACCOLADE clinical trial of avacopan for C3 Glomerulopathy (C3G) to date. The primary endpoint was change from baseline in the C3G Histologic Index for Disease Activity. Avacopan is an oral small molecule selective inhibitor of the complement C5a receptor Cf1R1.

Molecular Templates provided an update on the Phase I trial of MT5111, the company’s HER2 targeted ETB. So far, 16 patients have been treated in the dose escalation part of the trial, with a sixth initiated. PK data confirmed the predicted human PK based on non-human primate studies. There were no dose limiting toxicities observed. MT5111 is made up of a single chain variable fragment with affinity for HER2 fused to the enzymatically active de-immunized Shiga-like toxin-A subunit. It is being developed for HER2-targeted therapies and in patients with HER2-positive cancers, potentially as a way to overcome tumors that are resistant to existing HER2 therapies.

Amgen and AstraZeneca reported that their Phase III trial of Tezepelumab in asthma failed to hit its primary endpoint. The Phase III SOURCE trial evaluated the drug’s ability to create a statistically significant decrease in corticosteroid use on top of standard of care in some asthma patients. Tezepelumab is a potential first-in-class therapy that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine that plays a major role in asthma inflammation.

Acer Therapeutics announced full enrollment of trial evaluating the bioequivalence of ACER-001 compared to Buphenyl (sodium phenylbutyrate) for urea cycle disorders. ACER-001 is a taste-masked, immediate-release proprietary powder formulation for oral administration of sodium phenylbutyrate (NaPB) via suspension.

Rhythm Pharmaceuticals announced positive topline results from its Phase III trial of setmelanotide in Bardet-Biedl and Alstrom syndromes. Setmelanotide is a melanocortin-4 receptor (MC4R) agonist for treatment of insatiable hunger and severe obesity in individuals with the two syndromes. The study met its primary and all key secondary endpoints.

Polyphor received approval in the U.K. to initiate a Phase I trial of murepavadin to treat Pseudomonas aeruginosa infections in cystic fibrosis patients, including resistant bacterial strains. Murepavadin is an inhaled formulation using an eFlow Technology nebulizer.

ZIOPHARM Oncology received approval from the Taiwan regulatory authority to initiate a Phase I trial of patient-derived CD19-specific CAR-T. The approval was with Eden BioCell, a joint venture between Ziopharm and TriArm Therapeutics. It is being developed for relapsed CD19+ leukemias and lymphomas.

Bristol Myers Squibb reported that the independent Data Monitoring Committee (DMC) had reviewed its CheckMate -548 Phase III trial of Opdivo (nivolumab) plus current standard of care in patients with newly diagnosed glioblastoma multiforme (GBM) with 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation following surgical resection of the tumor. Unfortunately, the committee’s assessment indicated the trial would not meet its primary endpoint of overall survival (OS) in patients with no baseline corticosteroid use or in the overall randomized population. There were no safety concerns.

As a result, the company has decided to unblind the treatment assignments of patients in the trial. Patients will be provided information on their options for treatment going forward, and patients that were showing benefit from Opdivo can continue treatment if they and their physician agree.

Voyager Therapeutics announced the FDA had notified Neurocrine Biosciences it was playing a clinical hold on the RESTORE-1 clinical trial of NBiB-817. RESTORE-1 is a Phase II trial of an intracerebral AAV-based gene therapy for Parkinson’s disease. The delay is related after a Safety Report observed MRI abnormalities in some participants.

Rakuten Medical enrolled and treated its first patient in the U.S. in its Phase Ib/II trial of ASP-1929 Photoimmunotherapy in combination with anti-PD1 therapy in EGFR Expressing Advanced Solid Tumors. About 74 patients are planned for the trial in head and neck squamous cell carcinoma (HNSCC) and cutaneous squamous cell carcinoma (CuSCC). ASP-1929 is an antibody-drug conjugate made up of the antibody cetuximab and IRDye 700DX, a light activatable dye.

Evaxion Biotech dosed the first patient in a Phase I/IIa trial of its adjuvant immunotherapy EVX-02 in combination with checkpoint inhibitors in advanced melanoma. EVX-02 is a personalized cancer immunotherapy based on the unique genetic fingerprint of the individual’s tumor and it made up of patient-specific cancer neoepitopes incorporated into a DNA plasmid.

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