Like 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|
|Inovio and CEPI||Phase I||INO-4500||Lassa Virus||This Phase I study of placebo-controlled, blinded, dose-escalation design as well as the entire INO-4500 programme will be fully funded through a global partnership with Coalition for Epidemic Preparedness Innovations (CEPI). The sponsor intends to recruit approximately 60 volunteers to evaluate the safety, tolerability and immune responses of INO-4500.||The sponsor has published findings that this DNA candidate vaccine against Lassa fever provided 100% protection in a pre-clinical study with primates challenged with a lethal dose of the Lassa virus. In a recent press release published by the sponsor it was reported that their "synthetic nucleic acid platform of immunotherapies and vaccines deliver optimized synthetic antigen genes into cells with CELLECTRA® immune enhancing systems, where they are translated into protein antigens that activate an individual's immune system to generate robust targeted T cell and antibody responses."|
|Compugen, Ltd.||Phase I||COM701 in combination with Opdivo® (Nivolumab)||Advanced Solid Tumours||This is Phase I clinical trial, combining escalating doses of COM701 with a fixed dose of Opdivo® (Nivolumab) in patients with advanced solid tumours. The combination dose escalation arm was initiated following the evaluation of well-tolerated doses with no dose-limiting toxicities reported of COM701 from the monotherapy dose escalation arm of the trial. Bristol-Myers Squibb will provide the Opdivo® therapy, a PD-1 inhibitor, for the combination arms of the Phase I study. The primary endpoints of this Phase I trial are safety and tolerability.||The secondary endpoints of this study include preliminary anti-tumour activity, pharmacokinetics and pharmacodynamics. The trial will also evaluate evidence of preliminary antitumour activity of COM701 as monotherapy as well as in combination with Opdivo® in patients with selected tumour types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. It is expected that the sponsor will recruit approximately 140 patients across the US. COM701 is a first-in-class therapeutic antibody targeting Poliovirus Receptor-related Immunoglobulin (PVRIG), a novel immune checkpoint target candidate discovered computationally by the sponsor.|
|Atriva Therapeutics GmbH||Phase I||ATR-002||Influenza||This randomized, double blind dose escalation Phase I trial, is currently ongoing in Belgium. It will assess the safety and tolerability of ATR-002 in 60 healthy volunteers, randomized into three arms. According to the sponsor's Web site, this study will evaluate the safety and pharmacokinetic profile of ATR-002.||In their recently published press release, the sponsor stated that: "Preclinical data showed that an oral application of ATR-002 leads to the rapid and long-lasting inhibition of the Raf/MEK/ERK pathway and consequently, inhibition of reproduction of virus particles in the body. Compared to standard of care, absence of resistance formation and a longer treatment window were observed."|
|Axovant Gene Therapies, Ltd.||Phase I||AXO-AAV-GM1 (or AAV9-GLB1)||GM1 Gangliosidosis||On May 16 last month, the sponsor announced the dosing of its first patient in a Phase I clinical study of AXO-AAV-GM1 (also known as AAV9-GLB1), an investigational gene therapy for the treatment of GM1 gangliosidosis. The endpoints of this clinical trial will include safety, biomarker, neurodevelopment, Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) evaluations.||AXO-AAV-GM1 transports a functional copy of the GLB1 gene through an adeno-associated viral (AAV) vector, with the aim of regaining β-galactosidase enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is administered intravenously, which has the capacity to widely transduce the central nervous system and cure peripheral manifestations of the disease as well. Preclinical investigations in mice and a naturally-occurring feline model of GM1 gangliosidosis have supported AXO-AAV-GM1’s ability to enhance β-galactosidase enzyme activity, decrease GM1 ganglioside accumulation, ameliorate neuromuscular function, and prolong survival.|
|Dicerna Pharmaceuticals, Inc.||Phase I||DCR-HBVS||Chronic Hepatitis B Virus (HBV) Infection in Adults||This Phase I clinical trial (DCR-HBVS-101), is of a randomized, placebo-controlled design to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers and in patients with non-cirrhotic chronic HBV infection. As part of the study design, DCR-HBVS-101 will be divided into three groups/arms: In Group A, 30 HVs are to receive a single ascending-dose of DCR-HBVS (0.1, 1.5, 3, 6, or 12 mg/kg) or placebo, with a four-week follow-up period. Group B is a single-dose arm in which eight participants with HBV who are naïve to nucleoside analog therapy will receive a 3 mg/kg dose of DCR-HBVS or placebo; these participants will be followed for at least 12 weeks. The sponsor anticipates to initiate Group B dosing in the third quarter of 2019, in parallel with Group C at the 3 mg/kg dose level. Group C is a multiple ascending dose arm in which DCR-HBVS (1.5, 3, or 6 mg/kg) or placebo will be administered to 18 participants with HBV who are already being treated with nucleoside analogs, with a treatment and follow-up period of 16 weeks or more. The first participant dosed was from this group, at a dose of 1.5 mg/kg. Study participants in Groups B and C, in whom HBsAg will have dropped by more than 1 log10 IU/mL below baseline at their last scheduled study visit, will continue to be followed until their HBsAg level is less than 1 log10 IU/mL below the baseline value.||The secondary objectives of this study are to characterize the pharmacokinetic profile of DCR-HBVS and to evaluate preliminary pharmacodynamics and antiviral efficacy on plasma levels of hepatitis B surface antigen (HBsAg) and HBV DNA in blood. DCR-HBVS is composed of a single GalXC molecule that targets HBV messenger RNAs within the HBsAg gene sequence region. Preclinical studies with a standard mouse model of HBV infection demonstrated DCR-HBVS to yield greater than 99% reduction in circulating HBsAg, suggesting a level of HBsAg suppression (both in magnitude and duration of suppression) that may be greater than that achieved from targeting within the X gene sequence region.|
|NeuClone Pharmaceuticals, Ltd.||Phase I||Stelara® (Ustekinumab)||Moderate to Severe Plaque Psoriasis in Adults and Children 12 years or Older, Active Psoriatic Arthritis and Moderate to Severe Crohn’s Disease in Adults||This Phase I study is of a three-arm, randomised, double-blind, single-dose design with the primary objective to compare the pharmacokinetics and safety of NeuLara, the sponsor's Stelara® (ustekinumab) biosimilar to US- and EU-sourced Stelara® in healthy volunteers. This multicentre clinical trial of NeuLara will be performed in Australia under the Clinical Trial Notification (CTN) scheme of the Therapeutic Goods Administration (TGA).||The Stelara® biosimilar NeuLara was developed at the sponsor's facilities from its proprietary NeuMAX® technology and Right from the Start™ development approach. Stelara® (Ustekinumab) is a human monoclonal antibody approved for treatment of moderate to severe plaque psoriasis in adults and children 12 years or older. It is also approved to treat active psoriatic arthritis and moderate to severe Crohn's disease in adults. The efficacy of Stelara® (Ustekinumab) is directed against the inflammatory marker proteins interleukin-12 and -23, that regulate the immune system and immune-mediated inflammatory diseases.|
|ImaginAb, Inc.||Phase II||89Zr-Df-IAB22M2C||Cancer||This Phase II study will investigate the use of 89Zr-Df-IAB22M2C a first in class imaging agent that visualizes the immune system using non-invasive, whole-body in vivo PET imaging of CD8 T cells, to image CD8 T cells prior to (baseline) and after (on-treatment) of cancer patients undergoing immunotherapy-based treatment.||This clinical trial will recruit metastatic cancer patients and will evaluate the correlation of imaging signals observed using ImaginAb's CD8 T-cell ImmunoPET imaging agent, standard-of-care scans, and immunohistochemistry analysis of CD8 in biopsied tissues. The study will also monitor changes in CD8+ T-cell distribution before and after immuno-oncology therapies.|
|IO Biotech||Phase II||IO102 in Combination with KEYTRUDA® (Pembrolizumab)||Metastatic Non-Small Cell Lung Cancer (NSCLC)||Last month 15 May, the sponsor announced it has initiated the Phase II portion of a Phase I/II global, open-label, randomized clinical trial studying the investigational candidate IO102 in combination with KEYTRUDA® (Pembrolizumab) for the treatment of first-line patients with metastatic non-small cell lung cancer (NSCLC), the IO102-012/KEYNOTE-764 clinical trial. This is a global clinical trial anticipated to enrol 96 patients across more than 20 sites in the US and Europe||IO102, is an Indoleamine 2,3-dioxygenase (IDO) derived immune modulating candidate with a dual mechanism of action - annihilating both cancer cells and immune-suppressive cells. The sponsor's IDO-derived immune modulating therapies previously showed both a favourable safety profile and potential for anti-tumour activity in its first human clinical trial of heavily pre-treated patients with NSCLC.|
|Respivant Sciences||Phase IIb||RVT-1601||Idiopathic Pulmonary Fibrosis (IPF)||In this Phase IIb clinical trial (SCENIC trial), three different doses of RVT-1601 will be compared to placebo after 12 weeks of dosing. The objective primary endpoint of the study is the change in 24-hour cough frequency vs. placebo as measured by a cough monitor. It is a mult-centre trial being conducted at clinical sites in the U.S., Canada, and Europe and is anticipated to enrol up to 180 patients.||The secondary endpoints of this Phase IIb study include patient reported outcomes such as change in cough-related quality of life and cough severity. Following the double-blind treatment period, all enrolled patients will participate in a 12-week open-label treatment period on RVT-1601. In the Phase IIa portion of the clinical trial of 24 patients with IPF cough, the sponsor reported RVT-1601 to be "well tolerated and produced a statistically significant and clinically meaningful reduction in cough frequency". RVT-1601 is a proprietary inhaled formulation of a mast cell stabilizer with pleiotropic immune modulating activity delivered directly to the lungs via a proprietary electronic nebulizer device, the investigational PARI eFlow®. Distribution of RVT-1601 directly to the lung tissue of pulmonary fibrosis patients has potential for treating IPF cough as well as management of the underlying disease. The RVT-1601 mode of action is via inhibition of inflammatory mediators that contribute to cough and to the progression of fibrosis.|
|Rigel Pharmaceuticals, Inc.||Phase III||Fostamatinib Disodium Hexahydrate (Fostamatinib)||Warm Antibody Autoimmune Haemolytic Anaemia (AIHA)||This Phase III study of Fostamatinib is a placebo-controlled trial of roughly 80 patients to be enrolled with primary or secondary warm AIHA who have failed at least one prior treatment. The primary endpoint will be a durable haemoglobin response by week 24, defined as Hgb > 10 g/dL and > 2 g/dL greater than baseline and a durability of response measure, with the response not being attributed to rescue therapy. Enrollment is expected to take approximately 12 months.||Presently Fostamatinib is commercially available in the U.S. under the brand name TAVALISSE® (Fostamatinib Disodium Hexahydrate), which is the first and only spleen tyrosine kinase (SYK) inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. AIHA is a rare, debilitating blood disorder in which the immune system produces antibodies that result in the annihilation of the body's own red blood cells. Currently there are no disease-targeted medicines approved for AIHA.|
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