Clinical Catch-Up: November 11-15

Clinical research

It was a busy week for clinical trial announcements. Here’s a look.

ASLAN Pharmaceuticals announced topline data from its TreeTopp (TREatmEnT OPPortunity with varlitinib in biliary tract cancer) trial in second-line biliary tract cancer (BTC). The drug failed to meet the primary endpoints of progression-free survival (PFS) and overall response rate (ORR). Varlitinib is an oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors, HER1, HER2 and HER4. These receptors are mutated or overexpressed in numerous cancer types, resulting in excessive proliferation and uncontrolled growth.

Genentech, a Roche company, announced positive results from the pivotal Part II of the SUNFISH study of risdiplam in people aged 2-25 years with Type 2 or 3 spinal muscular atrophy (SMA). The trial met its primary endpoint of change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment compared to placebo. Risdiplam is an investigational, survival motor-neuron-2 (SMN2) splicing modifier.

Janssen Pharmaceutical, a Johnson & Johnson company, announced results from its Phase III CREDENCE study, finding that Invokana (canagliflozin) consistently decreased the risk of renal and cardiovascular (CV) events in patients with various levels of kidney function, or estimated glomerular filtration rates (eGFR). Invokana was approved by the FDA in September 2019 to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, CV death and hospitalization for heart failure (HHF) in adults with type 2 diabetes and diabetic kidney disease (DKD) with a certain amount of urine protein.

MyoKardia released new data from the PIONEER extension study of mavacamten for symptomatic, obstructive hypertrophic cardiomyopathy (HCM) and positive top-line data from the Phase II MAVERICK-HCM trial of mavacamten in non-obstructive HCM (nHCM). In the PIONEER-OLE study, the drug was well-tolerated through the one-year period and LVOT gradient, a measure of obstruction of the left ventricle, was consistently decreased in all 12 patients at all timepoints. In MAVERICK-HCM, the study hit its primary endpoint of establishing safety and tolerability of the drug in nHCM over 16 weeks.

BeyondSpring presented a poster on its novel trial design for Study 103 of plinabulin. The singled-blinded Phase III study 103 (DUBLIN-3) evaluated overall survival with plinabulin in combination with docetaxel versus docetaxel alone in stage IIIB/IV non-small cell lung cancer patients. The data showed that the single-blinded design statistically significantly prevented premature patient drop-out from the docetaxel arm compared to the JAVELIN study with avelumab.

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Flexion Therapeutics announced data from a sensitivity analysis evaluating the treatment effects of a single dose of Zilretta (triamcinolone acetonide extended-release injectable suspension) in patients with moderate-to-severe osteoarthritis (OA) pain. The findings suggest that pre-treatment concordance across two pain assays may act as a useful and important patient eligibility criterion for future clinical trials. Zilretta was approved by the FDA in 2017 as extended-release intra-articular therapy for patients with OA-related knee pain.

Mereo BioPharma announced 12-month topline data from its Phase IIb dose-ranging ASTEROID trial of setrusumab in Type I, III or IV osteogenesis imperfecta (OI). Sertrusumab is an anti-sclerostin antibody. The primary endpoint of the ASTEROID trial was change in Trabecular Volumetric Bone Mineral Density of the wrist over baseline after 12 months of treatments. The primary endpoint was not met at any of the three setrusumab dose values. There appears to be some concern that the new method of measuring the wrist, using High Resolution peripheral Quantitative Computed Tomography may have distorted the results. The study met an important secondary endpoint of increase in areal Bone Mineral Density at the lumbar spine at six and 12 months using two-dimensional dual-energy X-ray absorptionometry, a well-established measurements tool of BMD.

Celyad presented results from its NKG2D-based CAR-T clinical candidates for metastastic colorectal cancer, including its novel, off-the-shelf cell therapy CYAD-101 and alloSHRINK dose-escalation Phase I trial. “We are encouraged by the latest results from the alloSHRINK trial in metastatic colorectal cancer patients previously exposed to oxaliplatin- and irinotecan-based chemotherapies, including the tolerability profile and early antitumor activity of CYAD-101 with prior FOLFOX precondition chemotherapy,” said Frederic Lehman, vice president of Celyad’s Clinical Development & Medical Affairs. “In particular, the lack of clinical and laboratory evidence of graft-versus-host-disease for CYAD-101, which incorporates our proprietary T-cell receptor inhibitory molecule to reduce signaling of the TCR complex, establishes proof-of-concept for this industry-leading, off-the-shelf CAR-T approach. In addition, any host-versus-graft reaction against the allogeneic CAR-T product candidate appears to be controlled by the non-myeloablative FOLFOX chemotherapy. Overall, these encouraging data from the alloSHRINK trial warrant further evaluation of CYAD-101.”

Alnylam Pharmaceuticals initiated ILLUMINATE-C, a new global Phase III trial of lumasiran for primary hyperoxaluria type 1 (PH1). The trial will enroll patients of all ages with advanced renal disease. The primary study endpoint is the percent reduction in plasma oxalate from baseline to six months. Lumasiran is a subcutaneously administered RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1).

AstraZeneca and FibroGen presented pooled efficacy and cardiovascular safety analyses from the pivotal Phase III program of roxadustat for anemia from chronic kidney disease (CKD). The pooled CV safety data showed that roxadustat did not increase the risk of MACE, MACE+ and all-cause mortality in non-dialysis-dependent (NDD) compared to placebo and dialysis-dependent (DD) patients compared to epoetin alfa, a current treatment for anemia. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI).

Reata Pharmaceuticals announced that its Phase III  part of the CARDINAL trial of bardoxolone methyl (bardoxolone) in chronic kidney disease (CKD) caused by Alport syndrome hit its primary and secondary endpoints. Bardoxolone methyl is an experimental, oral, once-a-day activator of Nrf2, a transcription factor that induces molecular pathways involved in resolving inflammation. In the trial, patients receiving bardoxolone had a statistically significant improvement compared to placebo after 48 weeks in mean estimated glomerular filtration rate (eGFR). They also, after a four-week withdrawal period, had a statistically significant improvement compared to placebo in mean retained eGFR. The drug was well-tolerated.

AstraZeneca announced positive results from its Phase III TULIP 2 trial of anifrolumab in moderate to severe systemic lupus erythematosus (SLE). TULIP 2 randomized 365 eligible patients 1:1 to receive a fixed-dose intravenous infusion of 300mg anifrolumab or placebo every four weeks. The trial evaluated the effect of the drug in reducing disease activity as measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) composite measure. The drug showed superiority across multiple efficacy endpoints compared to placebo, with both arms receiving standard of care. The primary endpoint was statistically significant and clinically meaningful decrease in disease activity at week 52. In that group, 47.8% of the patients receiving anifrolumab responded compared to 31.5% of patients on placebo.

Eli Lilly and Company released data showing Taltz (ixekizumab) met the primary and all major secondary endpoints in COAST-X, a 52-week placebo-controlled Phase III trial of the drug for non-radiographic axial spondyloarthritis (nr-axSpA) in patients with objective signs of inflammation who are biologic disease-modifying anti-rheumatic drug naïve. A total of 303 adults with active nr-axSpA received Taltz or placebo. The Taltz group was superior to the placebo group.

Bellerophon Therapeutics announced positive initial data from its acute, dose escalation, clinical study of INOpulse for Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD). PHPF-002 is an ancillary study to its ongoing Phase II/III iNO-PF study. The results have shown clinically meaningful improvements in multiple pre-specified pulmonary hemodynamic parameters.

CytoDyn announced encouraging initial results from the first patient in a Phase Ib/II trial of leronlimab in metastatic triple-negative breast cancer. Circulating tumor cells in the patient’s blood decreased significantly after two weeks and five weeks of therapy. Leronlimab is a humanized IgG4 mAb that blocks CCR5.

GENFIT announced results showing that NIS4, the company’s non-invasive diagnostic blood tested to diagnose nonalcoholic steatohepatitis (NASH), outperformed other non-invasive NASH diagnostics in patients with type 2 diabetes. The data showed that of the patients in Cohort 1 type 2 diabetes is associated with increased prevalence of active NASH and significant fibrosis. The data from Cohort 2 showed the test significantly outperformed existing non-invasive diagnostics in accurately identifying NASH and significant fibrosis in type 2 diabetes patients.

GlaxoSmithKline announced positive results from its Phase III trial of Nucala (mepolizumab) in Hypereosinophilic Syndrome (HES). The trial met its primary endpoint, showing a statistically significant result where 50% fewer patients experienced a HES flare compared to placebo. Nucala was approved in 2015 for eosinophilic asthma. It is a first-in-class monoclonal antibody that targets IL-5.

Kiadis Pharma plans to discontinue development of ATIR101 and halt its ongoing Phase III trial. The trial was designed to show superiority of ATIR101 over the PTCy protocol. They found that a higher percentage of patients than expected dropped out of the study before receiving ATIR101, and further data showed PTCy outcomes were better than with ATIR101.

Millendo Therapeutics completed enrollment for the Phase IIb portion of its pivotal Phase IIb/III trial of livoletide in patients with Prader-Willi syndrome (PWS). The trial had over 150 patients recruited across 38 clinical trial sites globally. The trial is evaluating the safety and efficacy of livoletide on food-related behaviors in PWS patients. PWS is a genetic disease that, among other symptoms, includes uncontrollable hunger.

Samumed presented new clinical safety analysis of lorecivivant, a CLK/DYRK1A inhibitor that modulates the Wnt pathway. The drug appeared to be safe and well-tolerated in a pooled analysis of three controlled trials that evaluated the drug in a single intra-articular (IA) injection in patients with knee osteoarthritis (OA).

Zomedica Pharma expanded its pilot efficacy study of ZM-006 and initiated a partnership with University of Georgia’s (UGA) veterinary teaching hospital, to include Quakertown Veterinary Clinic. Methimazole oral formulation is a medical management of hyperthyroidism in cats. Zomedica’s ZM-006 is a transdermal gel designed to provide a single daily dose applied to a cat’s ear.

RemeGen announced a Phase IIb trial of RC18 Itelitacicept) for systemic lupus erythematosus (SLE). The trial met its primary endpoint of a greater than four-point decrease in the SLE Responder Index (SRI4). RC18 is a novel recombinant TACI-Fc fusion protein developed to treat autoimmune diseases.

Horizon Therapeutics announced integrated, pooled efficacy data from the Phase II and Phase III trials of teprotumumab for active thyroid eye disease (TED). The data support previous analyses of significant decreases in inflammation, eye bulging, and double vision, as well as improvements in quality of life. Teprotumumab is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor 1 receptor (IGF-1R).

AbbVie presented positive data from the Phase II/III SELECT-AXIS 1 trial of Rinvoq (upadacitinib) in active ankylosing spondylitis (AS). The trial met the primary endpoint of Assessment of SpondyloArthritis International Society (ASAS) 50 response at week 14 compared to placebo. Rinvoq is JAK inhibitor approved by the FDA for adults with moderately to severely active rheumatoid arthritis.

resTORbio announced topline data from the PROTECTOR 1 Phase III trial of RTB101 in clinically symptomatic respiratory illness (CSRI) in adults age 65 and older. The trial failed to meet its primary endpoint. The company halted development of the drug for respiratory disease, but will continue to test it in other areas, including Parkinson’s disease. RTB101 is an oral, selective, and potent TORC1 inhibitor. TORC1 inhibition has shown therapeutic benefit in preclinical research of aging-related diseases such as Parkinson’s disease.

Amgen and the Duke Clinical Research Institute (DCRI) announced plans to initiate the Cardiovascular Multi-dimensional Observational Investigation of the Use of PCSK9 inhibitors (cvMOBIUS) study, the first large-scale real-world trial to evaluate lipid management and the impact of PCSK9 inhibitors on cardiovascular outcomes. It will be run across the U.S. and Canada and begin patient enrollment this month. About 8,500 adults eligible for PCSK9 inhibitor treatment will be followed for five years. An electronic health record (HER)-based registry will run parallel to follow a broader adult population hospitalized with atherosclerotic cardiovascular disease.

Y-mAbs Therapeutics provided a clinical update on omburtamab for Desmoplastic Small Round Cell Tumor. DSRCT is an aggressive malignancy usually seen in intraabdominal sarcomatosis in young males. Data reported on 33 patients was positive for several parameters, including overall survival in combinations with several other therapeutics.

Anchiano Therapeutics discontinued its Phase II Codex trial evaluating the gene therapy inodiftagene vixteplasmid in BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC). Data analysis suggested there was a low probability of surpassing the defined futility threshold at the planned interim analysis.

Oncternal Therapeutics presented interim data from its Phase I trial of TK216 in relapsed or refractory Ewing sarcoma. The company indicated that one of two patients in the highest exposure dose cohort study is without evidence of Ewing sarcoma after eight months. TK216 is a first-in-class, targeted, investigational small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins.

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