Clinical Catch-Up: November 8-12
It was another busy week for clinical trial news. Here’s a look.
Boehringer Ingelheim enrolled the first patient in a new clinical trial in COVID-19 patients with respiratory failure. Weill Cornell Medicine and New York-Presbyterian Hospital are leading the study in whether these patients are more susceptible to developing progressive Interstitial Lung Disease (scarring of the lungs).
Synairgen reported it had hit its recruitment target of 610 participants for its global Phase III SPRINTER trial of SNG001 for hospitalized COVID-19 patients. The study is being run in 17 countries. The drug is an inhaled formulation of interferon beta, a broad-spectrum antiviral protein. A topline readout is expected in early 2022, and if successful, the company plans to file for an Emergency Use Authorization (EUA) in the U.S.
GlaxoSmithKline and Vir Biotechnology announced headline data from the COMET-TAIL Phase III trial of IM sotrovimab for mild-to-moderate COVID-19 in high-risk, non-hospitalized adults and adolescents. It was non-inferior to IV administration. Sotrovimab is a SARS-CoV-2 neutralizing monoclonal antibody.
Bristol Myers Squibb’s Phase III CheckMate -816 trial hit the primary endpoint in an interim analysis. The study was evaluating the company’s checkpoint inhibitor Opdivo (nivolumab) and chemotherapy in patients with resectable stage IB to IIIA non-small cell lung cancer (NSCLC), which is a neoadjuvant setting—a first step to shrink a tumor before the main treatment, typically surgery. The combination demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) compared to chemotherapy alone when dosed before surgery.
GlaxoSmithKline announced positive results in its Phase III trials of daprodustat. The drug, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor met the primary and secondary endpoints in the ASCEND-ND and ASCEND-D trials for anemia due to chronic kidney disease.
Novartis announced results from a pooled post-hoc analysis of Phase III ORION-9, -10, and -11 trials. The studies were looking at the impact of body mass index (BMI) levels on the safety and efficacy of twice-yearly Leqvio (inclisiran). The drug was well-tolerated and demonstrated effective and sustained reduction of about 50% in low-density lipoprotein cholesterol (LDL-C) when used with other lipid-lowering therapies. The company also presented positive Phase III results from the JUNIPERA study in support of Cosentyx (secukinmab) in pediatric patients with juvenile psoriatic arthritis (JPsA) and enthesitis-related arthritis (ERA). The drug significantly delayed time to flare versus placebo. The company also published data from HER-MES, a Phase IV study that compares Aimovig (erenumab) with an oral prophylactic migraine treatment (topiramate). Aimovig has a superior efficacy versus topiramate with patients having a significantly higher probability of having a clinically meaning improvement in migraine frequency.
Prelude Therapeutics reported the FDA had accepted its Investigational New Drug (IND) application for PRT2527. The company hopes to start a Phase I trial of the drug by the end of the year. PRT2527 is a potent and selective CDK9 inhibitor being developed for patients with selected solid tumors, including sarcoma, prostate cancer, breast cancer, and other cancers with genomic alterations that lead to MYC dependence.
TFF Pharmaceuticals completed dosing in the Phase Ib study of Voriconazole Inhalation Powder for treatment and prevention of Invasive Pulmonary Aspergillosis. The drug is a next-generation, direct-to-lung, inhaled dry powder version of voriconazole.
Selecta Biosciences announced topline results from a joint Selecta and AskBio Phase I trial of its ImmTOR platform to mitigate the formation of neutralizing antibodies against an adeno-associated viral serotype 8 serotype capsid used in gene therapies. At day 30, in patients receiving a single 0.3 mg/kg dose of ImmTOR, the company observed a median anti-AAV8 neutralizing antibody titer of 1:5, a 250-fold lower level than in subjects dosed with AAV8 capsid alone.
AstraZeneca presented three new sub-analyses from the DAPA-CKD Phase III trial of Farxiga (dapagliflozin). The drug is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. The data supports the consistency of the drug’s cardiorenal and mortality benefits in treating chronic kidney disease with and without type 2 diabetes.
Crinetics Pharmaceuticals presented new data from ACROBAT Advance, the ongoing open label extension (OLE) trial of paltusotine in patients with acromegaly. ACROBAT Edge and Evolve are two separate Phase II studies. Treatment with paltusotine resulted in median serum insulin-like growth factor-1 (IGF-1) levels that were lower than those observed in the untreated period in the parent studies and were stably maintained at levels achieved on prior SRL therapy for up to 51 weeks.
Affimed and NKGen Biotech initiated patient recruitment in the Phase I/IIa trial of the innate cell engager (ICE) AFM2 (Affimed’s tetravalent, bispecific EGFR and CD16A-binding ICE) in combination with SNK01, NKGen’s ex vivo expanded and activated autologous NK cell therapy.
iOnctura fully enrolled the metastatic uveal melanoma expansion cohort of the DIONE-01 trial of IOA-244. IOA-244 is a selective PI3Kδ inhibitor.
AbbVie presented integrated data from two Phase II trials, KEEPsAKE 1 and 2, of Skyrizi (risankizumab) in adults with active psoriatic arthritis. The data demonstrated that 24-weeks of treatment with the drug caused greater improvements in PsA signs and symptoms compared to placebo.
Eli Lilly reported sub-analysis of the EMPEROR-Preserved Phase III trial of Jardiance (empagliflozin) for adults with heart failure with left ventricular ejection fraction (LVEF) over 40%. The drug decreased the risk for the composite primary endpoint of cardiovascular death or hospitalization for heart failure and slowed kidney function decline regardless of chronic kidney disease status at baseline.
Rain Therapeutics plans to initiate a Phase II MANTRA-3 trial of milademetan as a monotherapy for Merckel cell carcinoma patients refractory to immune checkpoint inhibition. The drug is an oral mouse double minute 2 (MDM2) inhibitor. The trial is expected to start mid-2022.
SCYNEXIS completed its Phase I trial of a liposomal IV formulation of ibrexafungerp. The data support the safety of the liposomal IV formulation. Ibrexafungerp is an antifungal agent, a novel class of structurally distinct glucan synthase inhibitors, triterpenoids.
Neuroplast announced positive Phase I results in patients suffering from Traumatic Spinal Cord Injury (TSCI). The company’s Neuro-Cells appeared safe and well tolerated. The treatment uses the patient’s own stem cells to prevent further loss of function after sustaining TSCI.
Noxopharm initiated patient enrollment in its DARRT-2 Phase II trial. DARTT is an experimental immunotherapy based on Veyonda combining with a well-tolerated, low dosage of external beam radiotherapy to trigger an immune response.
Jasper Therapeutics and AVROBIO are collaborating on using Jasper’s JSP191, an anti-CD117 monoclonal antibody as a targeted conditioning agent for patients with Fabry disease and/or Gaucher disease type 1 who are receiving one of AvroBio’s ex vivo lentiviral gene therapies. JSP191 blocks stem cell factor receptor signaling.
Immutep announced final OS data from its Phase IIb AIPAC trial. The study evaluated eftilagimod alpha in combination with paclitaxel in metastatic breast cancer. The data supported Phase III development, with an OS benefit trend with median survival benefit of +2.9 months.
OncoC4 presented preliminary clinical data from the ongoing Phase Ia PRESERVE-001 trial of ONC-392 in cancer patients. ONC-392 is a nextgen anti-CTLA-4 monoclonal antibody.
Aravive announced positive new data from the Phase Ib portion of its open-label Phase Ib/II trial of batiraxcept (AVB-500) in combination with cabozantinib in clear cell renal cell carcinoma. Batiraxcept is a therapeutic recombinant fusion protein that neutralizes GAS6 activity by binding to GAS6, selectively inhibiting the GAS6-AXL signaling pathway, which is upregulated in multiple cancers including ovarian, renal and pancreatic.
CureVac announced promising data from the completed dose-escalation portion of the Phase I trial of CV8102. CV8102 is a single-stranded non-coding RNA optimized to maximize activation of cellular receptors that normally detect viral pathogens entering cells but is designed to recruit and activate antigen-presenting cells at the site of injection to present tumor antigens released from tumor cells to T cells in the draining lymph node.
89bio presented a sub-analysis of its Phase Ib/IIa proof-of-concept study of BIO89-100 in non-alcoholic steatohepatitis (NASH), looking at the correlation of liver fat and spleen volume. BIO89-100 is a potential best-in-class fibroblast growth factor 21 (FGF21) analog.
Athira Pharma presented an overview and updates from two ongoing Phase III trials, ACT-AD and LIFT-AD of ATH-1017 in mild-to-moderate Alzheimer’s disease. ATH-1017 is a small molecular designed to enhance the activity of Hepatocyte Growth Factor (HGF) and its receptor, MET.
AC Immune announced that Genentech presented the full topline data from the Phase III LAURIET trial of semorinemab in mild-to-moderate Alzheimer’s disease. The drug is an investigational anti-Tau monoclonal antibody. As previously announced, the trial hit one of two co-primary endpoints, demonstrating statistically significant 43.6% reduction in rate of cognitive decline, but missed the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) or the secondary efficacy endpoints.
Yumanity Therapeutics announced that YTX-7739 hit the primary endpoints in its Phase Ib trial in Parkinson’s disease. The drug is a potential first-in-class disease-modifying mechanism of action that inhibits stearoyl-CoA desaturase (SCD). It was generally well tolerated and demonstrated favorable PK/PD and safety profiles.
Apellis Pharmaceuticals presented data from the Phase III DERBY and OAKS trials of pegcetacoplan in geographic atrophy (GA) secondary to age-related macular degeneration. The drug is a targeted C3 therapy. It hit the primary endpoint in the OAKS study of significantly reducing GA lesion growth compared to pooled sham at 12 months. The DERBY study narrowly missed the primary endpoint, demonstrating a decrease in GA lesions growth with monthly and every-other-month treatment compared to pooled sham at 12 months.
Lindis Blood Care published results from the clinical pilot study of Catuvab for the removal of tumor cells from surgical blood. The results in 16 cancer patients undergoing abdominal tumor resection demonstrated efficacy and feasibility with no residual malignant cells detected in the final erythrocyte concentrates after the procedure. Catuvab is a medical device used to remove EpCAM-positive tumor cells from surgical blood and is designed to enable the use of machine autotransfusion technology (MAT).
Nouscom announced promising interim safety, immunogenicity, PK/PD and clinical activity data from the Phase I trial of NOUS-209. The drug is an off-the-shelf cancer vaccine based on shared neoantigens, administered in combination with Merck’s Keytruda (pembrolizumab) for Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction solid tumors.
Finch Therapeutics reported positive topline data from PRISM-EXT, an open-label extension of its PRISM3 Phase II trial of CP101 for prevention of recurrent C. difficile infection. There were no treatment-related serious adverse events, and the drug showed an overall safety profile consistent with what was seen in PRISM3.
Freeline Therapeutics announced new data from its ongoing Phase I/II MARVEL-1 dose-finding trial of FLT190 for Fabry disease. The data of the trial has seen expression of alpha-galactosidase A reaching near-normal levels.
HOOKIPA Pharma advanced HB-201 to Phase II. The drug is being evaluated in combination with Merck’s Keytruda (pembrolizumab) as a first or second-line treatment for HPV16+ squamous cell head and neck cancers (NHSCC). HB-201 is a single-vector compound with an arenavirus backbone that expresses an E7E6 fusion protein derived from HPV16.
Rafael Pharmaceuticals enrolled the first patient in the APOLLO 613 Phase I/II trial of CPI-613 (devimistat) in combination with hydroxychloroquine in patients with clear cell sarcoma at City of Hope in Duarte, Calif. Two other sites, Cleveland Clinic Children’s and University of Michigan’s Rogel Cancer Center have also been opened.
Adaptimmune Therapeutics reported updated clinical and translational data from its SPEARHEAD-1 Phase III trial of afamitresgene autoleucel in advanced synovial sarcoma or myxoid/round cell liposarcoma. Based on the reported overall response rate, it is expected to meet its primary endpoint in the final analysis planned later this year.
Merck initiated the VICTOR Phase III trial of Verquvo (vericiguat) in patients with chronic heart failure and reduced ejection fraction of 40% or less who have not had a recent worsening heart failure event. The drug is already approved in the U.S. to reduce the risk of CV death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient IV diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45%.
Eisai and Biogen presented results of sensitivity analyses evaluating the consistency of lecanemab efficacy across multiple statistical models in patients with Mild Cognitive Impairment (MCI) due to Alzheimer’s disease and mild AD. Lecanemab is an anti-amyloid beta protofibril antibody. Biogen also reported that its Aduhelm (aducanumab) significantly lowered plasma p-tau181, a biomarker of tau in Alzheimer’s disease. This was from two Phase III trials. They say change in plasma p-tau181 was significantly correlated with change in amyloid beta plaque, and it reduced cognitive and functional decline on all primary and secondary Alzheimer’s measurements.
Horizon Therapeutics enrolled the first patient in a Phase IIb trial of hZN-825 for diffuse cutaneous systemic sclerosis, a subset of systemic sclerosis (scleroderma). The drug is a lysophosphatidic acid receptor 1 (LPAR1) antagonist.
Ikena Oncology presented data from their IK-175 AHR antagonist program. The ongoing trial is recruiting patients in both monotherapy and combination cohorts with nivolumab. It is being evaluated in multiple tumor types, including urothelial carcinoma, a type of bladder cancer.
Vaccitech reported results from ongoing Phase I and Phase Ib/IIa trials of VTP-300 for chronic hepatitis B infection. The drug is a heterologous prime-boost vector combination of ChAdOx1-HBV + MVA-HBV. It induced robust T cells against targeted HBV antigens.
Cue Biopharma presented updated interim data from its ongoing trial of CUE-101 as a monotherapy for recurrent/metastatic HPV+ head and neck cancer. The drug is a Fc-fusion biologic that incorporates peptide-major histocompatibility complex molecules with engineered IL2.