Clinical Catch-Up: March 30 – April 3

Clinical Trials

Although a significant proportion of clinical trial news is related to the COVID-19 pandemic, companies are continuing to release clinical trial updates, although some of it is related to slowed or suspended enrollment. This Clinical Catch-Up has been split into three sections: COVID-19-Related Clinical Trials; Non-COVID-19-Related Clinical Trials; and Trials Affected by the COVID-19 Pandemic. Here’s a look.

COVID-19-Related Clinical Trials

Novartis announced that, with Incyte, it is launching a Phase III clinical trial to determine if their cancer drug Jakavi (ruxolitinib) can be used to treat COVID-19.

Jakavi is an oral inhibitor of the JAK1 and JAK 2 tyrosine kinases. It is approved for the treatment of polycythemia vera (PV) in patients resistant to or intolerant of hydroxyurea and for disease-related splenomegaly or symptoms in adults with primary myelofibrosis, post-polycythemia vera MF or post-essential thrombocythemia. Specifically, they are looking to see if Jakavi can be used to treat the cytokine storms associated with COVID-19. A cytokine storm is a massive immune overreaction that leads to the worst of the respiratory complications in COVID-19.

Bellerophon Therapeutics, which recently received expanded emergency authorization, treated the first patient with COVID-19 at the University of Miami School of Medicine with its INOpulse inhaled nitric oxide system (iNO).

CytoDyn has now treated 10 patients with leronlimab under an Emergency Investigational New Drug (EIND) by the FDA. The FDA also cleared the company to initiate a Phase II trial of leronlimab in COVID-19 patients with mild to moderate indications. The company filed a second clinical protocol for the drug to treat severely ill COVID-19 patients with leronlimab. The trial would be conducted under the same FDA-approved IND as its recently initiated Phase II trial in mild-to-moderate indications.

Murdoch Children’s Research Institute in Melbourne, Australia, is running a study into bacillus Calmette-Guerin (BCG) and COVID-19, which the World Health Organization (WHO) is encouraging other researchers to collaborate with. It will run six months; 4,000 healthcare workers will be vaccinated with BCG with the seasonal influenza vaccine or the influenza vaccine alone. A placebo vaccine isn’t being used because the BCG shot usually causes a localized skin reaction that leaves a scar.

Bionano Genomics launched the largest study to date to identify genomic variants and novel active substances that influence resistance or sensitivity to the novel coronavirus that causes COVID-19. The first study is underway in Wuhan, China. The Hannover Medical School is now launching a study involving 1,000 patients and controls.

Vaxart produced 5 COVID-19 vaccine candidates for testing in its preclinical models. Development has started on its development program for cGMP production of the vaccine with Emergent BioSolutions and expects to initiate a Phase I trial in the second half of 2020.

Applied Therapeutics announced its COVID-19 IND has been opened with the FDA for AT-001, a novel potent Aldose Reductase inhibitor in Phase III development for diabetic cardiomyopathy. It is being evaluated for acute lung inflammation and cardiomyopathy in critical COVID-19 patients.

Apeiron Biologics received regulatory approvals in Austria, Germany and Denmark to initiate a Phase II trial of APN01 for COVID-19. APN01 is the recombinant form of the human angiotensin-converting enzyme 2 (rhACE2).

Regeneron Pharmaceuticals and Sanofi announced they had treated the first patient outside of the U.S. with Kevzara (sarilumab) in severe COVID-19. The global clinical trial has been launched in Italy, Spain, Germany, France, Canada, Russ and the U.S. It is the second multi-center, double-blind, Phase II/III trial of Kevzara in COVID-19. Kevzara is a fully-human monoclonal antibody to the IL-6 receptor, an immune system protein produced in patients with rheumatoid arthritis. It is being evaluated in COVID-19 because of its ability to decrease the overactive inflammatory immune response seen in the disease, including markedly elevated levels of IL-6.

University Hospitals will head a clinical trial of ARMS-I to caregivers on the frontline of the pandemic, called the ARMS-I COVID Study. It will be conducted by the UH Clinical Research Center. ARMS-I is ARMS Pharmaceutical’s lead drug candidate for the prevention of airborne viruses.

Non-COVID-19-Related Trials

Merck announced the results from the Phase III VICTORIA trial of vericiguat in patients with heart failure with reduced ejection fraction and following a worsening event. The drug is being jointly developed with Bayer AG. Receiving the drug with available therapies resulted in a clinically relevant 4.2/100 patient-years absolute decrease in event rate—basically, fewer patients ended up in the hospital or died of heart failure.

Also, Merck’s checkpoint inhibitor Keytruda (pembrolizumab) hit one of the coprimary endpoints early in the Phase III KEYNOTE-177 clinical trial for a highly mutating form of colorectal cancer.

The trial is evaluating the drug in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer. Interim analysis by an independent Data Monitoring Committee (DMC) found that Keytruda alone showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy. The other dual primary endpoint is overall survival. The DMC recommended the trial continue without changes to evaluate OS.

Fractyl Laboratories announced clinical data on its Revita duodenal mucosal resurfacing (DMR) treatment in type 2 diabetes. Revita DMR is a same-day, outpatient endoscopic procedure that uses heat to resurface the lining of the upper intestine in a minimally invasive, outpatient procedure. The data from the REVITA-2 clinical trial showed that the treatment lowers blood glucose and reduces liver fat in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) compared to the sham procedure.

Biohaven Pharmaceutical announced positive topline data from its Phase III trial of oral rimegepant (Nurtec) for preventing migraine headaches in both episodic and chronic migraine patients. The primary endpoint was a statistically significant decrease from baseline in monthly migraine days compared to placebo.

Ovid Therapeutics announced initial data from its ongoing exploratory Phase II open-label ARCADE trial of soticlestat in patients with CDKL5 deficiency disorder (CDD) and Dup15q syndrome. Both are rare, highly refractory developmental and epileptic encephalopathies (DEE) with no approved treatment options. Soticlestat is a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H).

Immunovant announced positive results from the treatment phase of its ongoing Phase IIa trial of IMVT-1401 ASCEND GO-1 in patients with Thyroid Eye Disease (TED), also known as Graves’ ophthalmopathy. All the patients have completed treatment and have entered the follow-up phase. Mean reduction in total IgG levels from baseline to end of treatment was 65%.

Oyster Point Pharma completed enrollment in its pivotal Phase III ONSET-2 clinical trial of OC-01 nasal spray for the treatment of signs and symptoms of dry eye disease. It is a multicenter, randomized, double-masked, placebo-controlled trial to evaluate the safety and efficacy of the drug. Total enrollment was 758 patients. OC-01 is a highly selective nicotinic acetylcholine receptor (nAChR) agonist.

Novartis announced results from a prespecified analysis of pooled data from three Phase III trials of inclisiran for hyperlipidemia in adults. The pooled data of the ORION-9, -10, and -11 trials showed a durable and potent reduction in LDL-C of 51% when used with other lipid-lowering therapies over 17 months.

Horizon Therapeutics announced new pooled efficacy data from the Phase II and III trials of Tepezza (teprotumumab-trbw) showing the drug effectively reduces eye bulging in patients with Thyroid Eye Disease. The drug is approved for Thyroid Eye Disease.

Inovio Pharmaceuticals announced positive interim data from its Phase II trial of VGX-3100 in men and women with anal dysplasia, also known as high grade squamous intraepithelial lesion (HSIL). VGX-3100 is a DNA medicine for the treatment of HPV-16 and HPV-18 infection and precancerous lesions of the cervix.

Theranexus reported successful results from its Phase II trial for THN102 for Parkinson’s disease. The trial was looking at debilitating, excessive daytime sleepiness (EDS) from Parkinson’s disease. THN102 is a combination of modafinil and flecainide.

Akero Therapeutics announced that all three AKR-001 dose cohorts in its Phase IIa BALANCED trial in nonalcoholic steatohepatitis (NASH) met the primary endpoint of baseline in liver fat content at week 12, as well as the secondary endpoint of relative reduction in liver fat. AKR-001 is engineered to mimic the biological activity profile of native FGF21.

BioCardia said the independent Data Safety Monitoring Board (DSMB) had completed the prespecified data review of the Phase III pivotal CardiAMP Heart Failure Trial, said there were no safety concerns and recommended the trial continue. CardiAMP cell therapy uses a patient’s own bone marrow cells delivered to the heart in a minimally-invasive, catheter-based procedure.

Intellia Therapeutics reported that the FDA had accepted the IND application submitted by Novartis for its CRISPR-Cas9-based engineered cell therapy, OTQ923, for sickle cell disease. The Phase I/II trial will begin in adults with severe complications of SCD.

Blueprint Medicines announced topline data from its Phase I/II ARROW trial in RET-altered thyroid cancers. It plans to submit an NDA to the FDA in the second quarter. It also plans to submit an IND to the FDA for BLU-263, a next-generation KIT inhibitor for patients with indolent systemic mastocytosis (SM). Pralsetinib is a once-daily oral therapy targeting oncogenic RET alternations.

OSE Immunotherapeutics reported it had hit the primary endpoint in the predefined Step-1 analysis of its Phase III trial of Tedopi in HLA-A2 positive non-small cell lung cancer (NSCLC) after failure from checkpoint inhibitors. Tedopi is a proprietary combination of 10 neo-epitopes aimed at stimulating T-lymphocytes.

VBL Therapeutics announced positive interim analysis in the OVAL trial. Its Japanese licensee NanoCarrier Co. plans to extend the ongoing global Phase III trial in ovarian cancer to patients in Japan. The study is comparing a combination of VB-111 and paclitaxel compared to placebo plus paclitaxwel in patients with platinum-resistant ovarian cancer. VB-111 (ofranergene obadenovec) uses a dual mechanism to target solid tumors, combining blockade of tumor vasculature with an anti-tumor immune response.

Oncoceutics was informed that its Japanese licensee Ohara Pharmaceutical had dosed the first patient in a Phase I/II trial of OP-10 in adult and pediatric patients with high-grade glioma. OP-10 (also called ONC201) is an orally active small molecule DRD2 antagonist.

AXON Neuroscience presented positive results from its Phase II trial of AADvac1, the first tau vaccine to treat and prevent Alzheimer’s Disease. The drug showed a disease-modifying effect by reducing the neurodegenerative process by 58% compared to placebo as measured by Neurofilament Light Chain in the blood.

Biogen treated the first patient in its global clinical trial, DEVOTE, of Spinraza (nusinersen) when administered at a higher dose than presently approved for spinal muscular atrophy (SMA). The Phase II/III trial will be run at about 50 sites worldwide.

Mardil Medical successfully completed treatment of its third patient in the clinical trial of its improved VenTouch device. VenTouch is a combination therapy to treat the distorted valve, the dilated ventricle and displaced papillary muscles in patients with Type IIIb Functional Mitral Valve Regurgitation (FMR).

Oryzon Genomics presented data from two vafidemstat clinical trials in Alzheimer’s Disease, REIMAGINE-AD and ETHERAL. Both trials showed positive effects in reducing agitation-aggression (REIMAGINE-AD) and YKL40, an inflammatory biomarker. Vafidemstat is an oral, CNS optimized LSD1 inhibitor that seems to decrease cognitive and memory impairment as well as neuroinflammation.

Trials Affected by COVID-19 Pandemic

MediWound has temporarily suspended the initial of additional clinical sites and new patient enrollment in its U.S. EscharEx Phase II trial for venous leg ulcers. Existing sites will continue to manage randomized patients currently being treated, as well as enhanced safety measures, including remote site monitoring, virtual tools and digital communications. The NexoBrid expanded access (NEXT) program continues to enroll patients. The patient follow-up in the pivotal U.S. Phase III DETECT study of NexoBrid continues.

Amgen is evaluating its ongoing trials. The trial of AMGT 510, a KRAS inhibitor that is currently in a “potentially pivotal” Phase II trial in specific lung cancer patients. The company indicates it doesn’t expect any “significant delays,” and plans to continue its clinical trial program fairly uninterrupted, although there may be small delays depending on the course of the pandemic. The company’s Phase III trial in collaboration with AstraZeneca of tezepelumab in asthma is also fully enrolled and the company does not expect delays. And, the Phase III heart failure trial in collaboration with Cytokinetics of omecamtiv mecarbil is also fully enrolled and expected to continue uninterrupted.

Amgen also announced positive data from the  BEIJERINCK clinical trial of Repatha (evolocumab) in patients who are HIV-positive with high low-density lipoprotein cholesterol (LDL-C) despite stable background lipid-lowering therapy. The trial showed that Repatha significantly decreased LDL-C.

Reata Pharmaceuticals released an update on its clinical trials and business operations as a result. After consulting with the trial’s Data Safety Monitoring Board (DSMB), Reata has halted the Phase III CATALYST trial of bardoxolone methyl in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH).

The company’s Phase III CARDINAL trial of bardoxolone in patients with chronic kidney disease (CKD) caused by Alport syndrome is completely enrolled and ongoing. The study is continuing. Reata has launched at-home visits to collect blood samples and assess safety as an alternative to in-clinic visits when necessary. It has also set up home delivery of the study drug to the patient. Currently the company doesn’t think the pandemic will have a significant impact on completing the trial or its planned New Drug Application (NDA) for CARDINAL. The patients in CARDINAL are also eligible to enroll in an open-label extension study, EAGLE, which will have similar procedural changes as CARDINAL.

Reata has temporarily paused enrollment of the Phase III FALCON trial of bardoxolone in patients with autosomal dominant polycystic kidney disease (ADPKD). Patients already enrolled will continue. Reata is implementing similar procedures to the CARDINAL trial to ensure safety monitoring and drug delivery. It expects to continue patient screening and enrollment as soon as it can do so safely.

Exicure updated its response to the COVID-19 pandemic. Its Phase Ib/II trial of AST-008 in Merkel cell carcinoma and in cutaneous squamous cell carcinoma is beginning the Phase II, which is continuing as expected.

Momenta Pharmaceuticalstrial updates: Phase II VIVACITY-MG study of nipocalimab in generalized myasthenia gravis is fully enrolled and continuing; its Phase II UNITY trial of nipocalimab in hemolytic disease of the fetus and newborn (HDFN) continues to enroll patients at sites where it can be done and doesn’t intend to pause enrollment because of the life-threatening nature of HDFN, but does expect a slower pace of enrollment; its Phase II/III Energy Study of nipocalimab in warm autoimmune hemolytic anemia (wAIHA) is activating sites, but has temporarily suspended patient enrollment; and its M254 for intravenous immunoglobulin Phase I/II study in idiopathic thrombocytopenic purpura continues to enroll lower dose cohorts, but most of the sites have suspended enrollment.

Geron Corporation indicates that its IMerge Phase III trial in AML and high-risk MDS is ongoing, but there have been delays because of the pandemic. On a positive note, because of the slower completion and enrollment, it expects its 2020 operating expense burn to be lower than previously indicated.

Spring Bank Pharmaceuticals reports that its Phase Ia/Ib trial of SB 11285 in solid tumors is continuing, although some institutions involved have suspended patient enrollment. The company indicate sit is reviewing its portfolio of RIG-I agonists from its STING platform for COVID-19. These compounds have shown activity against viral respiratory diseases such as RSV, influenza and parainfluenza.

Fulcrum Therapeutics noted its ReDUX4 trial for Facioscapulohumeral Muscular Dystrophy is fully enrolled, but because some of the clinical sites are closed, the company is assessing its timeline for topline data.

CRISPR Therapeutics reported the pandemic is impacting several of its clinical trials, including two trials for CTX001 for severe hemoglobinopathies like transfusion-dependent beta thalassemia and severe sickle cell disease, because intensive care unit beds and related healthcare resources are expected to be overwhelmed, so they are not dosing patients at this time.

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