Clinical Catch-Up: October 21-25
Although the clinical trial news last week was dominated by the stunning reversal of Biogen and Eisai’s clinical trials of aducanumab for Alzheimer’s disease, there was plenty of other trial news. Here’s a look.
Biogen and Eisai announced that after discussions with the U.S. Food and Drug Administration (FDA), Biogen will pursue regulatory approval for aducanumab. The Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. The company now believes that data from a subset of patients in the trial who were given a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language. There were also benefits on activities of daily living—conducting personal finances, household chores like cleaning, shopping, and laundry, and independently traveling outside of the home.
The decision was based on new analysis run by Biogen in consultation with the FDA of a larger dataset from the trials halted in March. The larger dataset included data that became available after the independent monitoring committee’s recommendation.
Seattle Genetics announced positive results from its HER2CLIMB Phase III trial of tucatinib in combination with trastuzumab and capecitabine compared to trastuzumab and capecitabine alone in locally advanced unresectable or metastatic HER2-positive breast cancer. The HER2CLIMB trial met the primary endpoint of progression-free survival (PFS), showing that adding tucatinib to the treatment regime was superior to trastuzumab and capecitabine alone. There was a 46% decrease in the risk of disease progression or death by adding tucatinib.
Genentech, a Roche company, announced that its Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) hit the mark on its Phase III IMbrave150 trial in unresectable hepatocellular carcinoma (HCC) patients who have not receive previous systemic therapy. The trial met its co-primary endpoints, showing statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) compared to standard-of-care, Bayer’s Nexavar (sorafenib). Safety signals were consistent with those known for both Tecentriq and Avastin.
Abivax announced that data showed 75% of patients were in clinical remission after a 12-month open-label oral ABX464 Phase IIa maintenance trial in patients with moderate-to-severe active ulcerative colitis who had failed immunomodulators, anti-TNFalpha, vedolizumab and/or corticosteroids. The open-label study was conducted in 22 patients without treatment interruption after completing the randomized, double-blind, placebo-controlled 8-weeks induction study.
TLC presented data from its Phase I/II trial of TLC590 in pain reduction. The trial showed the drug, which utilizes the company’s proprietary lipid-assembled drug delivery platform (LipAD), yielded more immediate and long-lasting pain reduction than ropivacaine. It also showed no dose-related toxicity. TLC590 is a non-opioid, BioSeizer formulation of ropivacaine.
Protalix Biotherapeutics announced positive 12-month on-treatment data from the first 16 out of 22 adults enrolled in its BRIDGE Phase III trial. The trial is evaluating the safety and efficacy of PRX-102 (pegunigalsidase alfa) in Fabry disease patients currently treated with Replagel (agalsidase alfa) for at least two years and on a stable dose for at least six months. Fabry disease is an X-linked inherited disease caused by deficient activity of the lysosomal enzyme alpha galactosidase A. PRX-102 is a chemically modified stabilized version of the recombinant alpha-Galactosidase-A protein.
SQZ Biotech’s IND for SQZ-PBMC-HPV was granted clearance by the FDA. The trial will study its therapy, an SQZ-engineered APC to treat HPV+tumors. SQZ-PBMC-HPV is an autologous cell therapy engineered using the company’s Cell Squeeze platform. It is designed to present tumor antigens to the body’s endogenous CD8 T-cells.
Orchard Therapeutics announced initial data from a trial of its cryopreserved formulation of OTL-200, a gene therapy for metachromatic leukodystrophy (MLD). The data showed that cellular engraftment with OTL-200 using a cryopreserved formulation is similar to what was seen using a fresh formulation with the longest patients having 12 months of follow-up treatment.
ASLAN Pharmaceuticals enrolled the first patient in its multiple ascending dose (MAD) trial of its ASLAN004 in moderate to severe atopic dermatitis patients. ASLAN004 is a fully human monoclonal antibody that binds to the IL-13 receptor alpha1 subunit, which blocks the signaling of pro-inflammatory cytokines IL-4 and IL-13. The trial will start at Singapore’s National Skin Centre and Changi General Hospital.
Provention Bio’s PRV-6527 failed in a mid-stage clinical trial. PRV-6527, developed by Janssen and licensed to Provention Bio, is an oral Colony Stimulating Factor-1 Receptor (CSF-1R) small molecule inhibitor. The Phase IIa PRINCE trial enrolled 93 people with moderate-to-severe Crohn’s disease, 70% of whom were new to biologic therapy, or 30% who had been treated with at least one biologic drug ineffectively. The primary efficacy endpoint of the trial was change in the Crohn’s Disease Activity Index (CDAI) score at week 12. The drug showed what the company is calling a “substantial improvement in this symptom driven score” at the 12-week point, but it did not differentiate from placebo. The company argues that this high placebo response is related to the background medication about 85% of the patients’ biologic-naïve population were on.
MacroGenics announced topline data from the second pre-specified interim overall survival (OS) analysis of its Phase III SOPHIA trial of margetuximab in HER2-positive metastatic breast cancer who have previously received anti-HER2-targeted therapies. The drug is an immune-enhancing monoclonal antibody derived from MacroGenics’ Fc Optimization tech platform. In the intent-to-treat population, the median OS of patients receiving the drug and chemotherapy was prolonged by 1.8 months compared to patients receiving trastuzumab and chemotherapy.
Arena Pharmaceuticals presented new open-label extension data from the Phase II OASIS trial of etrasimod in moderately to severely active ulcerative colitis (UC). The drug is a next-generation, once-daily, oral, selective sphingosine 1-phosphate (S1P) receptor modulator. Most patients who achieved clinical response, clinical remission, or endoscopic improvement at week 12 also showed sustained or improved effects up to week 46 in the open-label extension of the trial.
Bellerophon Therapeutics presented new data from Cohort 1 of its ongoing Phase II/III trial of INOpulse for treatment of Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD). INOpulse is a proprietary pulsatile nitric oxide delivery system. The data showed benefit in moderate to vigorous physical activity (MVPA), overall activity and non-sedentary activity compared to consistent and significant deterioration in the placebo group.
Syros Pharmaceuticals provided updated clinical data from its ongoing Phase II trial of SY-1425 in combination with azacytidine in acute myeloid leukemia (AML) patients who are not eligible for standard intensive chemotherapy. SY-1425 is a first-in-class selective retinoic acid receptor alpha agonist. The interim data has demonstrated high complete response rates, rapid onset of action and a favorable safety profile in a genomically defined subset of newly diagnosed patients.
Rafael Pharmaceuticals announced that its Phase III trial of CPI-613 (devimistat) in metastatic pancreatic cancer is now active in four locations in South Korea. The trial recently enrolled 100 patients and is being operated in sites across the U.S., Israel and Europe. CPI-613 is a first-in-class compound that targets the mitochondrial tricarboxylic acid (TCA) cycle, which is essential to tumor cell multiplication and survival.
Mustang Bio dosed the first patient in its Phase I trial of MB-108 in recurrent glioblastoma multiforme. The first dosing took place at the University of Alabama at Birmingham. MB-108 (oncolytic virus C134) is an attenuated herpes simplex virus type 1. The trial is to determine its safety and efficacy and plans to enroll up to 24 participants.
SpringWorks Therapeutics dosed the first patient in the Phase IIb ReNeu trial of mirdametinib in children and adults with neurofibromatosis type 1-associated plexiform neurofibromas (NFI-PN). Mirdametinib is an oral, small molecule inhibitor of MEK1 and MEK2. NF1 has a global birth incidence of about one in every 3,000 people, with about 100,000 patients in the U.S. It is marked by mutations in the NF1 gene, which affects the MAPK pathway. About 30% to 50% of NF1 patients progress to develop plexiform neurofibromas, which are peripheral nerve sheath tumors.
Arcutis Biotherapeutics held a successful End-of-Phase II meeting with the FDA and announced plans to initiate its Phase III trial of ARQ-151 for plaque psoriasis. It completed enrollment of a 52-week Phase II long-term trial of ARQ-151 in that indication, with topline results expected in the first half of 2021. It expects to launch the Phase III trial in the first half of next year.
Zogenix announced positive new data for Fintepla (ZX008, fenfluramine) for seizures associated with Dravet syndrome. In five scientific posters presented at the Childhood Neurology Society (CNS) Congress, the data showed long-term, clinically meaningful decrease in convulsive seizure frequency in patients with Dravet syndrome under the age of six years. The data also showed clinically meaningful and “profound reduction” in high-risk tonic-clonic seizures in patients participating in the Phase III trial.
AMAG Pharmaceuticals published the results of PROLONG (Progestin’s Role in Optimizing Neonatal Gestation) in the American Journal of Perinatology. PROLONG is a clinical trial evaluating Makena (17-OHPC) in patients with a history of a previous spontaneous singleton preterm delivery. The trial was part of an approval commitment under the FDA’s “Subpart H” accelerated approval process. The trial did not meet the two co-primary endpoints of reduction of preterm birth and neonatal morbidity and mortality index.
Zai Lab Limited announced that its partner MacroGenics had dosed the first patient in the Phase II/III MAHOGANY trial of margetuximab in HER2-positive gastric cancer or gastroesophageal junction (GEJ) cancer. Margetuximab is an Fc-optimized monoclonal antibody targeting HER2. It is being investigated in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment.