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|
|Glenmark Pharmaceuticals||Phase I||CD38xCD3 Bispecific Antibody GBR 1342||Solid Tumors||On 7 November 2018, the sponsor announced commencement with a Phase I study in solid tumors for its CD38xCD3 bispecific antibody GBR 1342. This was initiated on the basis of a recently completed ex vivo translational study in multiple solid tumours utilizing the clinically validated CANscript™ platform, where treatment with GBR 1342 revealed predictive responses in various tumour types. GBR 1342 is part of the sponsor's proprietary BEAT® (Bispecific Engagement by Antibodies based on the T cell receptor) platform and simultaneously targets CD38 and the CD3 T cell co-receptor. This trial will assess the safety and tolerability of increasing doses of GBR 1342, and will also evaluate biomarkers, immunogenicity, and additional measures of disease activity.||GBR 1342 is part of the sponsor's proprietary BEAT® platform and simultaneously targets CD38 and the CD3 T cell co-receptor. CD38 is an antigen known to be involved in hematological malignancies as well as some solid tumours. BEAT® is the sponsor's proprietary technology for the production of bsAbs. With BEAT® technology, Glenmark's researchers have resolved past production obstacles encountered with bsAbs, and can efficiently manufacture these molecules at clinical and commercial scale.|
|BD||Phase I||LUTONIX® 014 Drug-Coated Balloon (DCB) IDE||Narrowed or Obstructed Arteries below the Knee||This LUTONIX® Drug-Coated Balloon (DCB) IDE, Phase I clinical trial for a below-the-knee (BTK) indication, is of a prospective, global, multicentre, randomized, controlled study design comparing the LUTONIX® 014 DCB to standard angioplasty for the treatment of narrowed or obstructed arteries below the knee. This trial made use of both proportional/binary and Kaplan Meier analyses to assess safety and efficacy. The primary safety endpoint—freedom from composite all-cause death, above the ankle or major reintervention of the treated limb through 30 days was met demonstrating a statistically significant safety equivalence between the LUTONIX® 014 DCB and standard PTA catheter, in both the proportional/binary and Kaplan Meier analyses.||"The primary efficacy endpoint investigated used a composite measurement of limbs saved from amputation and the openness of arteries, known as primary patency. By proportional/binary analysis, at six months there was an improvement in primary efficacy of 10.2% (DCB: 73.7% and PTA: 63.5%, p=0.0273, not-significant). The more commonly used Kaplan Meier analysis of the primary efficacy endpoint revealed a significant difference of 14.6% (DCB: 85.3%, PTA: 70.7%, p<0.001). Further analyses are planned for 12-, 24- and 36-month follow-ups.|
|OncoSec Medical||Phase IIb||TAVO™ (in combination with Merck’s KEYTRUDA®)||Late-stage Triple Negative Breast Cancer (TNBC)||The sponsor reported on 6 November preliminary data from KEYNOTE-695, a global, multicentre Phase IIb, open-label study of intratumoral delivery of TAVO™ (tavokinogene telseplasmid / IL-12) with intravenous KEYTRUDA® (pembrolizumab) in patients with unresectable, advanced melanoma. Of the first nine subjects to complete 12 weeks of treatment and reach initial tumour evaluation (by RECIST v1.1), two subjects had a partial response, while one subject had disease stability (22% BORR and 33% DCR) and tumour responses occurred in both TAVO™ treated and untreated lesions.||From 1 September 2018, 21 patients had been enrolled in the study. Out of the 21 patients, nine patients had completed 12 weeks of treatment and reached the first tumor evaluation point at approximately 12 weeks, while the remaining 12 patients had not yet reached the first tumor evaluation. All nine patients were previously treated and definitively progressed on anti-PD-1 therapies with 56% (5/9) having had more than one prior line of therapy. All enrolled patients had exceedingly low frequencies of intratumoral CD8+ peCTL (PD-1+/CTLA-4+) at screening with a notable increase in TIL density following treatment. Of the two responding patients, both had multiple prior rounds of anti-PD-1 therapy, with no response, and one had also progressed after 4 cycles of OPDIVO® and YERVOY® (ipilimumab), an FDA-approved anti-CTLA4 / anti-PD-1 antibody combination. Therapy responses were associated with treatment-related upregulation of immune-based transcripts in the tumor microenvironment, as well as increased frequencies of intratumoral T cells within three weeks of therapy.|
|Themis Bioscience||Phase II||MV-CHIK||Chikungunya Fever (CF)||Themis Bioscience recently completed a Phase II study designed to assess the safety, tolerability and immunogenicity of MV-CHIK to protect against CF. The trial, which included 263 healthy participants, was conducted at four study sites in Austria and Germany. The primary endpoint, defined as the presence of neutralizing antibodies against Chikungunya, four weeks after administration of one or two MV-CHIK injections, was met across all treatment groups. The study demonstrated that MV-CHIK induced neutralizing antibodies against Chikungunya in all treatment groups after two injections, with seroconversion rates ranging from 86.4% to 100.0%, depending on dose and administration schedule. The data also demonstrated that pre-existing antibodies against the measles vaccine virus did not affect immunogenicity against Chikungunya. Adverse events related to the vaccine were highly similar between groups with no serious effects recorded.||Currently CF, a mosquito-transmitted disease, has no treatment or prevention options and was recently added to the Tropical Disease Priority Review Voucher Program of the FDA. The double-blinded, randomized, placebo- and active comparator- controlled Phase II study also evaluated the impact of pre-vaccination against the vector in two groups that received Priorix®, the live attenuated measles, mumps and rubella (MMR) vaccine, prior to MV-CHIK administration.|
|Endo International Plc||Phase IIb||Collagenase Clostridium Histolyticum (CCH)||Edematous Fibrosclerotic Panniculopathy (EFP or more commonly "Cellulite")||This Phase IIb study enrolled 375 women with moderate or severe EFP (cellulite) aged 18 years or older in the United States. Each subject received up to three treatment sessions of CCH (0.84 mg / session) or placebo with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment quadrant – left or right buttock or left or right posteriolateral thigh. At both the outset and conclusion of the study period (28 days after the last treatment), EFP severity was examined by each patient and clinician using two photonumeric EFP severity scales developed by the sponsor and other third-party experts. The scales – the Photonumeric Cellulite Severity Scale (PCSS) – are 5-point scales ranging from 0 (no EFP) to 4 (severe EFP) that measure improvement in the appearance of EFP. The study's primary endpoint was the proportion of composite responders at Day 71 defined as subjects with a 2-point improvement in severity from baseline in the clinician-reported (CR) PCSS and a 2-point improvement in the patient-reported (PR) PCSS. Subjects receiving CCH showed statistically significant levels of improvement in the appearance of EFP with treatment, as measured by the trial's primary endpoint (p<0.001), compared to those subjects receiving placebo.||Additional endpoints included a composite of 1-point responders, the percentage of responders with 1-point and 2-point improvements on the CR-PCSS and PR-PCSS, assessment of improvement by patient and clinician using the Global Aesthetic Improvement Scale (GAIS); subject satisfaction, and change in the Hexsel cellulite severity scale. CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area; 92 percent of all related AEs were mild to moderate in the CCH group compared to 96 percent in the placebo group; the most common AEs were expected and included injection site bruising (approximately 75 percent) and injection site pain (approximately 59 percent).|
|Urovant Sciences, Inc.||Phase III||Vibegron||Overactive Bladder (OB)||The sponsor recently announced it has completed enrollment for an international Phase III study, EMPOWUR, which will be evaluating the safety and efficacy of Vibegron as a treatment for adults with OB. EMPOWUR has enrolled a total of 1,530 patients meeting the inclusion criteria and these subjects will be randomized across 216 study sites into one of three groups for a 12-week treatment period with a four-week safety follow up period: Vibegron 75 mg administered orally once daily; placebo administered orally once daily; or tolterodine ER 4 mg administered orally once daily. The study will have co-primary endpoints which are: 1) Change from baseline in the average number of micturitions per 24 hours in all patients and 2) Change from baseline in the average number of urge urinary incontinence (UUI) episodes per 24 hours in patients who have one or more UUI episodes per day prior to treatment.||Vibegron is an investigational oral therapy acting as a beta-3 adrenergic agonist. The EMPOWUR Phase III study is of a randomized, double-blind placebo- and active comparator controlled design to be investigated in men and women with symptoms of overactive bladder, including frequent urination, sudden urge to urinate, and urge incontinence or leakage. Also as an extension study, the first 507 patients who complete the EMPOWUR trial will be enrolled in a 40-week double-blind trial to evaluate the safety of longer-term treatment of Vibegron.|
|AVEO Oncology||Phase III||Tivozanib||Highly Refractory Advanced or Metastatic Renal Cell Carcinoma (RCC)||On 5 November 2018, the sponsor announced it has met primary end point for its TIVO-3 trial, a Phase III randomized, controlled, multi-centre, open-label study to compare Tivozanib (FOTIVDA®) to sorafenib in 351 subjects with highly refractory advanced or metastatic RCC. The study met its primary endpoint by demonstrating a statistically significant benefit in progression-free survival (PFS). Tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02). Median PFS was 5.6 months for Tivozanib compared to 3.9 months for sorafenib. Additionally the TIVO-3 study enrolled patients with RCC who have failed at least their two previous regimens. Among these, approximately 26% of patients received checkpoint inhibitor therapy in earlier lines of treatment. Tivozanib PFS was longer than sorafenib both in patients who received prior checkpoint inhibitor therapy and those who did not.||Tivozanib is administered orally acting as a VEGF receptor tyrosine kinase inhibitor. As for the secondary endpoint analysis of overall survival (OS), this outcome was not mature at the time of the final PFS analysis, with only 46% of potential OS events having been reported. At the time of the preliminary OS analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02). Tivozanib was generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous Tivozanib trials. Infrequent but severe adverse events reported in greater number in the Tivozanib arm were thrombotic events similar to those observed in previous Tivozanib studies. The most common adverse event in patients receiving Tivozanib was high blood pressure, an adverse event known to reflect effective VEGF pathway inhibition.|
|Eli Lilly||Phase III||Trulicity||non-fatal Cardiovascular (CV) Death, non-fatal Myocardial infarction (MI) and non-fatal Cerebrovascular Accident (CVA) in Type II Diabetes||The sponsor announced on 5 November 2018, that Trulicity® (Dulaglutide) significantly reduced major adverse cardiovascular events (MACE), a composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke in its REWIND study. The REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) study was a multicentre, randomized, double-blind, placebo-controlled trial designed to assess the effect of Trulicity 1.5 mg, a weekly glucagon-like peptide 1 receptor agonist (GLP-1 RA), compared to placebo, both added to standard of care, on cardiovascular (CV) events in adults with type 2 diabetes. The primary CV outcome was the first occurrence of MACE (the composite of CV death or non-fatal myocardial infarction or non-fatal stroke). The REWIND study revealed a median follow-up period of more than 5 years, the longest for a CV outcome trial in the GLP-1 receptor agonist class. In comparison, other CV outcome trials had more people with a higher baseline A1C (a marker of % glycated heamoglobin) of and a greater percentage of patients who had established CV disease.||The REWIND secondary outcomes included each component of the primary composite CV outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. This was an international study of 9,901 subjects from 24 countries who had a mean duration of diabetes of 10 years and a mean baseline A1C of 7.3 percent. Thirty-one percent of subjects had prior (or established) CV disease at baseline. Prior CV disease in REWIND was defined as prior myocardial infarction, prior ischemic stroke, prior unstable angina, prior revascularization (coronary, carotid, or peripheral), prior hospitalization for ischemia-related events (unstable angina or myocardial ischemia on imaging, or need for percutaneous coronary intervention), or prior documented myocardial ischemia.|
|Bone Therapeutics||Phase III||PREOB||Hip Osteonecrosis (ON)||Bone Therapeutics recently decided to stop its PREOB Phase III trial following the recommendations of the Data and Safety Monitoring Board (DSMB) citing that at final analysis the primary objective is likely not to be achieved. The Phase III study investigated 44 patients who have ON of the hip. In an interim examination of the trial data, the DSMB said treatment with PREOB, an autologous osteoblastic cell therapy derived from patient bone marrow, was well-tolerated, but not as effective as aniticpated by the sponsor.||As a follow up to the termination of the Phase III study of PREOB, the sponsor has indicated that it will focus its cell therapy development activities and resources on its off-the-shelf, allogeneic platform, ALLOB. The sponsor also cited that allogenic cells are differentiated cells that are derived from ex vivo cultured bone marrow cells from healthy donors, claiming such cells have demonstrated stronger osteogenic properties than PREOB cells.|
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