aLike many aspects of healthcare business space, drug development is in a state of constant change for the purpose of better health outcomes. Here is a summarised report of new drug therapies currently in clinical trials worldwide as from this week.
|Sponsor||Study Phase||Drug Name/Code||Clinical Indication||Status||Comment|
|NeuClone||Phase I||NeuLara||Plaque Psoriasis, Psoriatic Arthritis, Crohn’s Disease and Ulcerative Colitis||This Phase I clinical trial of single-dose, double-blind, randomised, three-arm study design is being conducted across multiple Australian sites in over 200 healthy volunteers. The primary objective is to demonstrate equivalent pharmacokinetics (PK) of NeuLara to US- and EU-sourced Stelara®.||The secondary objective of this study is to demonstrate equivalent safety of NeuLara to US- and EU-sourced Stelara®. In preclinical investigations, NeuLara has been extensively tested to confirm structural and functional similarity in comparison to the reference product Stelara®. These investigations included positive PK and safety results from a non-clinical primate study, as well as physicochemical analyses of Stelara® and NeuLara. NeuLara is under clinical development as a biosimilar candidate of Ustekinumab, an antibody targeting interleukin-12 and -23, approved under the brand name Stelara® to treat patients with plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.|
|Alder BioPharmaceuticals, Inc.||Phase I||ALD1910||Migraine||This Phase I clinical trial of double-blind, placebo-controlled study design will recruit approximately 100 healthy men and women between the ages of 18 and 55 and will evaluate the safety, tolerability and pharmacokinetic profile of ALD1910 at various doses.||ALD1910 is an investigational monoclonal antibody (mAb) representing a potential new therapeutic mode of action, focusing on a new pathway in migraine prevention, different to the usual mechanism of inhibiting the calcitonin gene-related peptide (CGRP), a neuropeptide believed to mediate and initiate migraine attacks. In lieu, ALD1910 in preclinical studies was shown to inhibit pituitary adenylate cyclase-activating polypeptide (PACAP), an important signaling molecule in the pathophysiology of migraine.|
|Amphivena Therapeutics, Inc.||Phase I||AMV564||Various Cancers||Earlier this month, 15th October, the sponsor announced that over 50 patients have received AMV564 in two Phase I clinical trials|
for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). AMV564, a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3, is currently being evaluated in a Phase I clinical trial in patients with relapsed/refractory AML at five different medical research centres in the U.S..
|The sponsor states that AMV564 has shown novel clinical activity by rapidly and selectively eliminating leukaemic blasts and rare immature, granulocytic and monocytic MDSCs while leaving normal CD33-expressing cells in tact, including neutrophils and monocytes. AMV564 is also being assessed in a Phase I solid tumour study which is currently open to recruitment.|
|Nektar Therapeutics||Phase I||NKTR-255||Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM)||This Phase I clinical trial is of an open-label, dose escalation and dose expansion study design in patients with selected haematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will assess the safety and tolerability of NKTR-255 as monotherapy in roughly 40 patients in order to ascertain a recommended Phase II dose (RP2D) for NKTR-255. The dose expansion phase of the study will recruit in two separate cohorts: the first cohort will recruit patients with MM or NHL (relapsed salvage) to evaluate the NKTR-255 RP2D as a monotherapy and the second cohort will recruit patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, Daratumumab.||As secondary study objectives, the trial will also assess pharmacokinetic and pharmacodynamic effects, anti-tumour activity and biomarker assessments. NKTR-255 is an IL-15 receptor agonist designed to trigger the IL-15 pathway and expand NK cells and promote the survival and proliferation of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may impact on a sustained anti-tumour immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which undergoes rapid systemic clearance and therefore is required to be administered frequently and in high doses, limiting its utility due to toxicity and inconvenience of administration.|
|Hope Biosciences||Phase I/II||HB-adMSCs||Traumatic Brain Injury (TBI) and Hypoxic-Ischemic Encephalopathy (HIE).||This Phase I/II clinical trial is of a single arm, non-randomized study design that is anticipated to recruit 24 subjects. The primary objective of the study is to determine the safety and treatment effect of HB-adMSCs for treatment of sub-acute and chronic TBI and HIE. HB-adMSCs are administered via three intravenous infusions over a six-week period and follow-up assessments at six months and one-year post-infusion. HB-adMSCs are autologous and have an established safety profile.||Presently there are no therapies that have demonstrated clinical benefit in chronic TBI. Chronic neuroinflammation has been demonstrated after neurological injury for up to 13 years in patients after TBI and is associated with progressive white matter loss. HB-adMSCs are expected to provide immunomodulation to reduce chronic microglial activation as measured by [11C]ER-176 uptake value measurements systemically and in the thalamus. Overall results are anticipated to be a decrease in neuronal cell loss and improvements in neurocognitive outcomes (improvements in verbal response, motor function, and memory, that correlate to physical changes in the brain).|
|DiaMedica Therapeutics Inc.||Phase II||DM199||Chronic Kidney Disease (CKD)||This Phase II clinical trial is of a multi-centre, open-label study design of roughly 60 patients with CKD, who will all be recruited in the U.S. to two cohorts across 10 clinical sites. The two cohorts of the study will be patients with CKD caused by IgAN and non-diabetic, hypertensive African American patients with CKD. African Americans are at higher risk for CKD than Caucasians, and African Americans who have the mutated APOL1 gene are at an even more greater risk. The study is designed to capture APOL1 gene mutation as an exploratory biomarker. The study will evaluate two dose levels of DM199 within each cohort. Enrolled patients will receive DM199 by subcutaneous injection twice weekly for 95 days . The primary endpoints of the study include safety, tolerability, blood pressure and kidney function, which will be evaluated by changes from base line in eGFR and albuminuria, as measured by the urinary albumin to creatinine ratio (UACR).||DM199 is a synthetic recombinant equivalent of the human serine protease kallikrein (KLK1). The KLK1 protein plays a key function in the regulation of various physiological processes in the kidneys, including blood flow, inflammation, fibrosis and oxidative stress. The sponsor proposes that DM199 restores KLK1 levels, enabling the natural physiologic process of the body to selectively release bradykinin-mediated nitric oxide, prostaglandins (PGE2 and PGI2-cAMP) and other anti-inflammatory mediators in the kidneys, which consequently work synergistically to improve renal blood flow (dilating both afferent & efferent arterioles) thus slowing down inflammation, oxidative stress and fibrosis. The sponsor also claims that DM199 possibly is involved in restoring the body’s natural ability to regulate the function of the epithelial sodium channel (ENaC), thus keeping systemic sodium levels in check.|
|PhaseBio Pharmaceuticals||Phase IIb||PB2452 with low-dose Aspirin||Reversal of Blood Thinning (Antiplatelet Activity)||This Phase IIb clinical trial is of a multi-centre, randomized, double-blind, placebo-controlled study design to assess the safety and efficacy of PB2452 in reversing the antiplatelet effects of Ticagrelor as part of a dual antiplatelet regimen including low-dose aspirin. Also, this Phase IIb study signifies the beginning of the FDA's aligned registrational trials to support the submission of a Biologics License Application (“BLA”) for a possible accelerated approval of PB2452. Roughly a 200 older and elderly cohort (ages 50 to 80) of patients are anticipated to be recruited, resembling the patient population most likely to be treated with Ticagrelor and potentially benefit from PB2452, if registration is granted. Patients will be randomized in a ratio of 3:1 and will receive either PB2452 or placebo, with roughly 150 participants receiving PB2452. The primary endpoint of the trial is reversal of the antiplatelet effects of Ticagrelor with intravenous infusion of PB2452 or placebo, as measured by a proprietary VerifyNow® PRUTest® biomarker.||PB2452 is a novel, recombinant, human monoclonal antibody antigen-binding fragment with an intended efficacy to reverse the antiplatelet activity of Ticagrelor in major bleeding and urgent surgery situations. Ticagrelor is an antagonist of the P2Y₁₂ receptor, licensed by Astra Zeneca. In a Phase I clinical trial, PB2452 showed potential to derive life-saving therapeutic benefit through immediate and sustained reversal of Ticagrelor’s antiplatelet activity, mitigating concerns pertaining to bleeding risks associated with the use of antiplatelet medicines. At present there are no approved reversal agents for Ticagrelor treatment or any other antiplatelet therapies.|
|Can-Fite BioPharma Ltd.||Phase II||Namodenoson||Nonalcoholic Steatohepatitis (NASH)/Nonalcoholic Fatty Liver Disease (NAFLD)||This Phase II clinical trial is of a multicentre, randomized, double-blinded, placebo-controlled, dose-finding efficacy and safety study design recruiting 60 patients with NAFLD with or without NASH. Patients who suffer from NAFLD/NASH with evidence of active inflammation are dosed twice daily with 12.5 mg or 25 mg of oral Namodenoson, or placebo for 12 weeks. The study primary endpoint is the anti-inflammatory effect of the drug, as determined by mean percent change from baseline in ALT (alanine aminotransferase) blood levels and safety. The study secondary endpoint will be the percentage change from baseline of liver fat, as measured by MRI-PDFF (proton density fat fraction).||Namodenoson is a small orally bioavailable drug that binds selectively with high affinity to the A3 adenosine receptor (A3AR). Namodenoson is being assessed as a second line therapy for hepatocellular carcinoma, with a recently completed Phase II trial and planned Phase III trial for the same clinical indication. A3AR is found highly expressed in diseased cells whereas low expression exists in normal cells. This differential effect is the rationale for such a superior safety profile of the candidate medicine.|
|Denovo Bipharma LLC||Phase IIb||DB102||Glioblastoma also known as Glioblastoma Multiforme (GBM) in combination with radiation therapy and Temozolomide||On 15 October of this month, the sponsor announced FDA's approval to initiate Denovo's Phase IIb clinical study of DB102 in patients with newly-diagnosed GBM in combination with radiation and Temozolomide, an alkylating chemotherapy agent used as a first-line treatment for GBM.||This clinical trial represents an extension of the work to identify a genetically-enriched patient population with diffuse large B-cell lymphoma (DLBCL) who could possibly benefit from DB102 treatment. Upon the sponsor acquiring the licensing rights of DB102 from Eli Lilly & Co., it discovered a novel genetic biomarker, DGM1, that is a potentially predictive biomarker for DB102 response in patients with DLBCL. As DGM1 is a germline biomarker, the sponsor reports also that DGM1 predicts a survival benefit in patients with GBM treated with DB102 plus Temozolomide. This clinical trial is anticipated to recruit 200 newly-diagnosed GBM patients.|
|Boehringer Ingelheim||Phase II||BI 1265162||Cystic Fibrosis (CF)||Earlier this month, 16 October, the sponsor announced the first patient has been recruited in its Phase II clinical trial BALANCE-CFTM 1 to evaluate a new potential treatment for CF. The study will evaluate how different doses of its candidate drug BI 1265162, an inhaled epithelial sodium channel (ENaC) inhibitor, impacts lung function compared to placebo when added to the standard of care in adults and adolescents with CF.||The ENaC inhibitor is intended as a therapy for patients of all types of CF mutations. It is administrated via the Respimat® inhaler, which is the proprietary platform inhaler of Boehringer Ingelheim. The Respimat® inhaler actively delivers medicine in a slow-moving soft mist that is easy to inhale even for people who have difficulty breathing. People with cystic fibrosis often have a high treatment burden, sometimes spending hours administrating multiple treatments.The rapid inhalation of BI 1265162 ENaC inhibitor via Respimat® that can be administered anywhere is intended to be added to the standard of care.|
|Imbrium Therapeutics||Phase II||IMB-115||Insomnia Associated with Alcohol Cessation (IAAC)||This Phase II clinical trial of randomized, double-blind, placebo-controlled, multi-centre, parallel-group study design will evaluate the compound’s safety, efficacy, and tolerability in adults with moderate or severe alcohol use disorder who are experiencing IAAC. Participants will receive IMB-115 (1 mg or 2 mg) or placebo, administered orally at bedtime for three weeks. The primary outcome of the study is to evaluate change from baseline of wakefulness after sleep onset (WASO), as measured by polysomnography (PSG). Secondary outcome measures of the study include changes from baseline related to sleep efficiency, latency, total sleep time, and number of awakenings.||IMB-115 is a novel compound discovered by the sponsor with a novel mechanism of action undergoing clinical development for the treatment of insomnia disorders, including IAAC. Insomnia associated with alcohol cessation is a major challenge for certain patients recovering from alcohol use disorder in their plight to sustain abstinence from alcohol use and currently there are no FDA-approved pharmacological treatment options to help these patients address this challenge.|
|Amygdala Neurosciences||Phase II||ANS-6637||Alcohol Use Disorder (AUD)||This Phase II clinical trial is of a three-arm, double-blind, randomized, placebo-controlled, parallel group, three-site study design to evaluate the effects of ANS-6637 as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. The study will recruit 81 patients seeking treatment who meet DSM-5 criteria for at least moderate alcohol use disorder. Endpoints include laboratory paradigm alcohol cue-elicited alcohol craving, percentage of subjects with no heavy drinking days, percentage of subjects abstinent from alcohol, and safety.||ANS-6637 is a selective and reversible aldehyde dehydrogenase 2 (ALDH2) inhibitor, a novel chemical entity with a first-in-class mechanism of action for treating substance use disorder. Based on its mechanism of action in the brain to prevent pathophysiologic dopamine surge without changes to basal dopamine, the sponsor states that ANS-6637 has the potential to prevent drug seeking behaviour, craving and relapse. The sponsor has acquired the licensing rights to ANS-6637 as a spin-out from Gilead Sciences.|
|Novavax Inc.||Phase III||NanoFlu||Influenza||This pivotal Phase III clinical trial will assess the safety and immunogenicity of NanoFlu using the sponsor’s proprietary Matrix-M adjuvant in adult patients aged 65 years and above compared to the quadrivalent influenza vaccine licensed in the U.S.. The study's primary objective is to demonstrate non-inferior immunogenicity as measured by haemagglutination inhibition (HAI) titres of vaccine homologous influenza strains compared to seasonal marketed influenza vaccine.||Earlier this year in January, the sponsor announced top-line data from a phase II study on NanoFlu. Results from the same clinical trial showed that NanoFlu improved immune responses in adults aged 65 years or older compared to Sanofi’s leading influenza vaccine Fluzone High-Dose.|
|SurgiMab||Phase III||SGM-101||Colorectal Cancer (CRC)||This randomized Phase III study, has been designed following discussions with the FDA and other regulators and is anticipated to recruit 300 CRC patients in ten clinical centres across Europe and the U.S.. The trial will evaluate the safety and clinical benefit of using fluorescence-guided surgery (FGS) with SGM-101 as an intraoperative imaging agent to better identify cancer lesions during the surgical procedure. Participants are administered with 10mg of SGM-101 by injection four days before the scheduled CRC surgical procedure.||SGM-101 is a tumour-specific antibody conjugated to a fluorophoric dye component that fluoresces under near-infra-red light; it selectively targets a marker on the surface of cancerous cells known as carcinoembryonic antigen (CEA), which is overexpressed by more than 95% of colorectal cancer cells. SGM-101 is being developed to provide oncology surgeons with a novel intraoperative imaging tool designed to improve the visualization of tumour tissues overexpressing CEA in real-time during surgery. The study objective is to demonstrate that SGM-101 could be implemented to enable surgeons to more clearly delineate the margin between cancerous and healthy tissue. This clinical trial is also investigating if SGM-101 use could minimize or circumvent removal of healthy tissue adjacent to tumour cells in order to improve functional outcomes.|
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