Clinical Catch-Up: COVID-19, AAN, ACC
It was a very busy week for clinical trial news, in part because of presentations coming out of the American Academy of Neurology (AAN) and American College of Cardiology (ACC) meetings. Here’s a look.
Merck and Ridgeback Biotherapeutics presented data from 3 studies of Lagevrio (molnupiravir), an oral antiviral. All were from the Phase II/III MOVe-OUT trial. One study demonstrated that the drug is effective at reducing the risk of progression of COVID-19 in non-hospitalized, unvaccinated patients at high risk of poor outcomes. A second study was conducted on immunocompromised patients. Of the 1,433 participants in the MOVe-OUT trial, 4% were immunocompromised. In the group receiving molnupiravir, only 8% of the immunocompromised patients were hospitalized or died by Day 29 compared to 25% in the placebo group. And in the third, the drug demonstrated superiority over placebo in non-hospitalized adults with mild or moderate COVID-19 at risk of progression to severe disease. This was dependent upon patients starting the medication within five days of onset of symptoms.
Kintor Pharmaceutical announced topline results from its Phase III MRCT trial of proxalutamide in outpatients with mild to moderate COVID-19. The study evaluated the patients regardless of vaccination status or risk factors. The study demonstrated that the drug, when given to the patients for more than seven days, offered a protection rate of 100%. It reduced hospitalization or death in COVID-19 patients, notably in the middle-aged and elderly with high-risk factors. Proxalutamide is an ACE2 and TMPRSS2 inhibitor.
Tonix Pharmaceuticals announced the FDA had cleared its IND for a Phase II trial for TNX-102 SL as a potential treatment for a subset of patients with Long Covid Syndrome, whose symptoms overlap with fibromyalgia. TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride.
United Biomedical-Asia published results from the Phase I/II and Phase I extension trial of its Multitope SARS-COV-2 Subunit Vaccine, UB-612, against the Omicron and Delta COVID-19 variants. The vaccine elicited long-lasting B- and T-cell immunity.
Talaris Therapeutics presented new data on COVID-19 outcomes in living donor kidney transplant (LDKT) patients receiving FCR001, the company’s cell therapy product. The data was from the company’s Phase II trial. The new data is a retrospective chart review of patients in the study performed by investigators at Northwestern University, who analyzed COVID-19 infection rates, the effects of the infection, and evidence of antibody response to vaccination. There were 28 patients for whom data were available, and 23 were durably chimeric. All of these 23 were able to discontinue chronic immunosuppression. The five remaining patients were not durably chimeric and continued on chronic immunosuppression.
Ionis Pharmaceuticals and AstraZeneca presented positive results from the Phase IIb ETESIAN trial of ION449 to reduce blood cholesterol levels. The drug is an antisense therapeutic that targets proprotein convertase subtilisin/kexin type 9 (PCSK9). ETESIAN hit its primary endpoint, reducing serum LDL-C levels by 79%. Both the 50mg and 90mg doses achieved statistically significant and clinically meaningful decreases in LDL-C levels from baseline of 77% and 79%, respectively, compared to 2% in the placebo group. Those decreases remained until Week 14, or six weeks after the last dose. The drug was generally well-tolerated.
Pfizer’s vupanorsen demonstrated modest reductions in non-HDL cholesterol in adults who were already receiving statins. It decreased non-HDL by up to 28% but lowered triglyceride levels by up to 57%, and ANGPTL3 by up to 95%. Its effects on LDL and apolipoprotein B (apoB) levels were modest. Vupanorsen lowers non-HDL by decreasing the production of ANGPTL3, a protein that inhibits metabolic enzymes related to triglyceride and cholesterol. The data was from the TRANSLATE-TIMI 7088 trial.
Sanofi and Regeneron Therapeutics’ Praluent (alirocumab), when added to high-intensity statin therapy in the PACMAN-AMI trial, demonstrated improved coronary plaque regression and stabilization when initiated early after an acute myocardial infarction (MI). The combination offered better decreases in percent atheroma volume and lipid burden in addition to a greater increase in minimal fibrous cap thickness.
Silence Therapeutics’ Phase I APOLLO trial of SLN360 decreased Lp(a) levels. SLN360 is the company’s wholly owned siRNA experimental therapeutic. siRNA therapies are designed to temporarily block a specific gene’s encoding that would otherwise cause an unwanted biological effect. SLN360 is designed to silence LPA, a gene that codes for a specific protein only found in lipoprotein(a)[Lp(a)].
NeuroDerm Ltd., a wholly owned subsidiary of Mitsubishi Tanabe Pharma, announced positive, long-term safety and tolerability data from the Phase IIB BeyoND trial of ND0612. It is an investigational drug-device combination that provides minimally invasive, continuous subcutaneous infusion of liquid levodopa/carbidopa for patients with Parkinson’s disease experiencing motor fluctuations. The data demonstrated the treatment was safe and well tolerated over the long term.
Genentech, a Roche company, announced new Ocrevus (ocrelizumab) data demonstrating the drug’s benefit on disease progression and cognitive outcomes in primary progressive multiple sclerosis (PPMS) and secondary progressive MS (SPMS). Ocrevus is a humanized monoclonal antibody targeting CD20-positive B cells.
Paracrine published findings from the STAR I trial of its autologous Adipose-Derived Regenerative Cell (ADRC) Therapy in patients with either diffuse cutaneous scleroderma (dcSSc) or limited cutaneous scleroderma (IcSSc) with hand dysfunction. The primary endpoint was a change in hand function at 24 and 48 weeks. The study did not meet its primary endpoint but provided findings that helped design and choose endpoints for the STAR II trial, a Phase III trial.
Inozyme Pharma announced positive preliminary biomarker, safety and PK data from the first three patients in the Phase I portion of its Phase I/II trial of INZ-701 in adults with ENPP1 Deficiency. All patients showed rapid, significant and sustained increases in PPi levels. INZ-701 is an enzyme replacement therapy for mineralization disorders of the circulatory system, bones, and kidneys.
Cytokinetics announced full results from the METEORIC-HF Phase III trial of omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF). Patients receiving the drug had an average change from baseline in pVO2of -0.2 ml/kg/min compared to 0.2 ml/kg/min in patients on placebo. The therapy is a small molecule cardiac myosin activator.
Bristol Myers Squibb announced results from an extended EXPLORER-LTE trial of the long-term effects of mavacamten. The EXPLORER-HCM Phase III study concluded in 2020, where the data demonstrated positive outcomes for the patients in the extended trial. The drug is being evaluated for symptomatic obstructive hypertrophic cardiomyopathy. It is a cardiac myosin inhibitor.
CymaBay Therapeutics published results from the Phase II trial of seladelpar in primary biliary cholangitis. Seladelpar is a selective peroxisome proliferator-activated receptor-delta agonist. Interim primary efficacy analysis of ALP change from baseline at Week 8 demonstrated the drug provided 26%, 33% and 41% reductions for the 2mg, 5mg and 10mg doses, respectively.
Vaxcyte dosed the first participants in the Phase II portion of its ongoing Phase I/II trial of VAX-24 for the prevention of invasive pneumococcal disease (IPD) and pneumonia in adults. The initiation occurred after the independent Data Monitoring Committee completed a review of the Phase I data and recommended the Phase II portion continue as planned.
ReAlta Life Sciences announced an excellent safety profile and confirmed target engagement in its Phase I trial of RLS-0071 being developed for hypoxic-ischemic encephalopathy. It is a complement inhibitor and an innate anti-inflammatory product.
PhaseBio Pharmaceuticals announced complete results from its Phase II trial of bentracimab patients who were pretreated with dual antiplatelet therapy made up of ticagrelor and low-dose aspirin. Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in patients with uncontrolled bleeding or need of surgery.
Innovent Biologics announced the results of a Phase III trial of IBI306. The drug is a recombinant fully human anti-PCSK-9 monoclonal antibody that is being evaluated in Chinese patients with heterozygous familial hypercholesterolemia.
Biolojic Design announced that the first-ever computationally-designed human antibody will enter the clinic. The company will study AU-007 in solid cancer tumors. The antibody has been transferred to its spinoff, Aulos Bioscience, which is now running clinical trials in Australia. AU-007 targets interleukin-2 (IL-2).
Imara announced failed sickle cell and beta-thalassemia trials and plans to discontinue development. Specifically, the company announced results from interim analyses of its Ardent Phase IIb trial of tovinontrine in sickle cell disease (SCD) and the Forte Phase IIb trial of the same drug in beta-thalassemia. Tovinontrine is a highly selective and potent small molecule phosphodiesterase-9 (PDE9) inhibitor. Its multimodal mechanism of action acts on red blood cells, white blood cells, adhesion molecules and blood vessels. PDE9 degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule associated with vascular biology.
Novartis announced new long-term data from the Phase III ASCLEPIOS I/II trials and the ALITHIOS open-label extension demonstrating long-term efficacy and safety of Kesimpta (ofatumumab) with continued reduced risk of disability worsening for people with relapsing MS after up to four years treatment.
Nurix Therapeutics dosed the first patient in its Phase I trial of DeTIL-0255 in patients with advanced gynecological malignancies, including ovarian, cervical and endometrial cancers. DeTIL-0255 is a drug-enhanced tumor infiltrating lymphocyte therapy.
Nouscom presented new translational data from the ongoing Phase I trial of NOUS-209. The drug is an off-the-shelf cancer immunotherapy targeting shared neoantigens administered with Merck’s Keytruda (pembrolizumab) for Microsatellite Instable High (MSI-H) gastric, colorectal and gastro-esophageal junction solid tumors.
Sequana Medical completed implanting patients in the Phase III POSEIDON pivotal trial in support of the alfapump system for recurrent or refractory ascites due to liver cirrhosis. Of the 71 patients in the Pivotal Cohort, 40 have been implanted.
Cara Therapeutics announced biomarker data from the KALM-1 and 2 clinical trials of Korsuva (difelikefalin) injection for chronic kidney disease-associated pruritus (itching) in patients undergoing hemodialysis. Korsuva is the first and only FDA-approved treatment for moderate-to-severe pruritus associated with CKD in adults undergoing hemodialysis.
Theravance Biopharma reported mixed results from Study 0170 of ampreloxetine to reduce symptomatic neurogenic orthostatis hypotension (nOH). It did not show improvement in the overall population but did with a subset of patients with multiple system atrophy (MSA). Ampreloxetine is a long-acting, oral norepinephrine reuptake inhibitor.
WAVE Life Sciences reported a positive update on its Phase Ib/IIa trial of WVE-004 for amyotrophic lateral sclerosis (ALS). The drug was effective across all dose levels tested.
Respira Therapeutics dosed the first patient in the Phase IIb VIPAH-PRN trial of RT234 in pulmonary arterial hypertension (PAH). The drug is vardenafil administered as a dry powder inhaled treatment.
Allergan announced positive topline results from the Phase III trial of twice-daily administration of Vuity (pilocarpine HCl ophthalmic solution) 1.25% in adults with age-related blurry near vision (presbyopia). It hit the primary efficacy endpoint, improving near vision without compromising distance vision at Hour 9 on Day 14.
Bond Biosciences dosed the first patient in a Phase Ia/b trial of BBI-001 for hemochromatosis. The drug is designed as a non-absorbed oral therapeutic to bind dietary iron and inhibit iron absorption.
Processa Pharmaceuticals enrolled the first patient in its Phase IIa trial of PCS12852 in patients with moderate to severe gastroparesis, a chronic gastric motility disorder. The drug is a novel, potent, and highly selective 5-hydroxytryptamine-4 receptor agonist.
Citius Pharmaceuticals reported positive topline data from its Phase III trial of I/Ontak (denileukin diftitox) for persistent or recurrent cutaneous C-cell lymphoma (CTCL). I/Ontak is an engineered interleukin-2 (IL-2) diphtheria toxin fusion protein. The primary outcome measured was the objective response rate (ORR), which demonstrated ORR of 42.3%.
CNS Pharmaceuticals received approval from France’s regulatory body to run a pivotal Phase III trial of berubicin for recurrent glioblastoma multiforme (GBM). Berubicin is a novel anthracycline.
Avadel Pharma, which Flamel Technologies acquired, published positive secondary endpoint data from its pivotal Phase III REST-ON trial of FT218. The drug is an investigational formulation of sodium oxybate to be taken once at bedtime for the treatment of excessive daytime sleepiness or cataplexy in adults with narcolepsy.
Abivax reported positive data from the interim analysis of its Phase IIb open-label maintenance study of ABX464 for ulcerative colitis. The drug has a novel mechanism of action based on the upregulation of a single, specific micro-RNA with anti-inflammatory properties called miR-124.
Acutis Biotherapeutics enrolled the last subject in its Phase III ARRECTOR trial of topical roflumilast foam in adolescents and adults with scalp and body psoriasis. The drug is a once-daily, topical formulation of a highly potent and selective PDE4 inhibitor (roflumilast).
Aptinyx announced that its Phase IIb trial of NYX-2925 for diabetic peripheral neuropathy (DPN) failed to hit the primary endpoint. NYX-2925 is a novel, oral NMDA receptor-positive allosteric modulator (PAM). They will continue developing the drug for fibromyalgia.
Tonix Pharmaceuticals enrolled the first participant in the Phase III RESILIENT trial of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) for management of fibromyalgia. An Independent Data Monitoring Committee will conduct an interim analysis of the first 50% of patients enrolled in the first quarter of 2023.
Annexon completed enrollment in the Phase II ARCHER study of ANX007 in geographic atrophy. ANX007 is an anti-C1q candidate.
Abionyx Pharma reported positive interim results from an open-label Phase IIa RACERS trial of CER-001 for septic patients at high risk of developing Acute Kidney Injury (AKI). Compared to the standard of care, CER-001 quickly improved biomarkers of inflammation, including leukocytosis and endothelial dysfunction, preventing septic patients from going into acute kidney injury.
Janssen presented Phase II data of nipocalimab for generalized myasthenia gravis (gMG). The data demonstrated that serum IgG levels can be utilized as a supportive biomarker to manage the disease.