Clinical Catch-Up: Moderna COVID-19 Vaccine for Kids and Much More
Although it was relatively quiet in COVID-19-related clinical trials, there was plenty of other clinical trial news. Here’s a look.
Moderna reported positive interim results from the Phase II/III KidCOVE trial of its mRNA COVID-19 vaccine in children six months to under two years and two years to under six years of age. The data showed a “robust neutralizing antibody response” in both cohorts.
The doses were lower, a 25-microgram, two-shot series, than the 100 microgram doses used in adults. The immunogenicity of the 25-microgram doses was similar to those observed with the 100-microgram two-dose shots in adults 17 to 25 years. During the study period, Omicron (BA.1) was the dominant variant in the U.S. In children six months to two years, efficacy was 43.7% and in two years to six years it was 37.5% against infection. Any infections seen were mild, with no severe cases observed. There were zero incidents of severe disease, hospitalizations or death.
ImmunoGen announced positive Phase III results of mirvetuximab soravtansine alone in patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer in patients previously treated with Avastin (bevacizumab). The Phase III SORAYA trial is a single-arm study of the drug in patients with platinum-resistant ovarian cancer whose cancers expressed high levels of FRα who had been treated with one to three previous regimens, at least one of them being Avastin.
The primary endpoint was confirmed objective response rate (ORR) evaluated by the investigator, and a key secondary endpoint was duration of response (DOR). ORR for the study was 32.4%, including five complete responses (CRs). ORR was 31.6%, including five CRs. The response rates were consistent no matter the number of previous lines of therapies or use of PARP inhibitors the patients had.
Vallon Pharmaceuticals announced that its Phase III SEAL trial of ADAIR for the treatment of attention deficit hyperactivity disorder (ADHD) failed to hit its primary endpoint. ADAIR is a proprietary abuse-deterrent formulation of immediate release (IR) dextroamphetamine. Dextroamphetamine is the active ingredient used in Adderall and other FDA-approved treatments for ADHD. The primary endpoint was Emax Drug Liking. ADAIR’s score was similar to what had been observed in an earlier proof-of-concept trial, but reference dextroamphetamine didn’t score as high as expected and as had been observed in the previous trial. As a result, the results of the SEAL study did not hit statistical significance.
Cortexyme presented new data from the Phase II/III GAIN trial of COR388 (atuzaginstat) to treat mild to moderate Alzheimer’s disease. The data described target engagement data showing the drug inhibited lysine gingipains, which demonstrated a 30% to 50% slowing in cognitive decline in participants with high P. gigivalis load. It also described numerical trends in traditional Alzheimer’s disease biomarkers, including phosphor-tau 181 and total tau.
NeuroSense Therapeutics announced the FDA had cleared its IND for PrimeC, a potential therapeutic for amyotrophic lateral sclerosis (ALS). PrimeC is made up of ciprofloxacin, a well-known antibiotic, and celecoxib, an FDA-approved nonsteroidal ant-inflammatory. The IND is for a Phase I trial.
Zai Lab announced positive data for its Phase III PRIME trial of Zejula (niraparib) for ovarian cancer patients who had already received platinum-based chemotherapy. Zejula is a poly (ADP-ribose) polymerase (PARP) inhibitor.
Tonix Pharmaceuticals announced it is halting enrollment in the Phase III RALLY trial after a futility analysis of the first 50% of patients failed to generate a statistically significant outcome in fibromyalgia patients. The drug, TNX-102 SL (cyclobenzaprine HCl sublingual tablets), is designed to provide rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine.
Cali Biosciences offered successful results in its Phase IIb trial of CPL-01, a perioperative long-acting analgesic, injectable version of Naropin (ropivacaine hydrochloride). It is being evaluated to treat post-operative surgical pain. It reported an excellent dose-response for efficacy.
uniQure completed patient enrollment in the first two cohorts of its Phase I/II trial of AMT-130 for Huntington’s disease. The treated patients have received a single administration of AMT-130 using MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). AMT-130 is made up of a recombinant AAV5 vector carrying a DNA cassette encoding a microRNA that lowers Huntingtin protein in Huntington’s disease patients.
KemPharm completed an analysis of the full data set from its Phase I study of serdexmethylphenidate (SDX) delivered at higher doses than those previously studied. SDX is the company’s prodrug of d-methylphenidate (d-MPH) for idiopathic hypersomnia (IH).
Turning Point Therapeutics hit its enrollment target of 40 patients for the EXP-6 cohort of the Phase I/II registrational TRIDENT-1 study for NTRK-positive TKI-pretreated advanced solid tumor patients. EXP-6 (reprotrectinib) is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of NSCLC and advanced solid tumors.
Aligos Therapeutics halted the development of ALG-020572, which was being developed in patients with chronic hepatitis B (CHB). The first CHB cohort of Study ALG-020572-401 was stopped after one of the patients had a serious adverse event (SAE), causing a brief hospitalization. The patient showed a significant increase in alanine aminotransferase (ALT) after multiple dosing of 210 mg of the therapy. They noted that this was just one of four CHB subjects in the cohort to have the potentially drug-related ALT flares indicative of liver toxicity, which they were not expecting based on nonclinical research and Phase I studies in healthy volunteers. ALG-020572 is a GalNAc-conjugated antisense oligonucleotide (ASO).
Vertex Pharmaceuticals announced it was advancing its VX-147 into pivotal development for proteinuric kidney disease mediated by two mutations in the APOL1 gene (AMKD). The primary endpoint is a reduction in the rate of decline of kidney function as measured by the estimated glomerular filtration rate (eGFR) slope versus placebo at approximately two years.
Visus Therapeutics launched the first of two pivotal Phase III Trials for Brimochol PF for presbyopia. Presbyopia is loss of near vision associated with aging. The drug is designed to produce a “pinhole effect” that reduces the size of the pupil and allows the light rays focused on the retina to enter the eye, sharpening vision.
Plus Therapeutics dosed the first patient in the ReSPECT-LM Phase I/IIa trial of Rhenium-186 NanoLiposomem for leptomeningeal metastases (LM). The drug is a proprietary nanoscale compound with a unique chelated radioisotope administered locally as a single dose via a conventional Ommaya reservoir.
Pfizer reported that etrasimod hit the market in the Phase III ulcerative colitis ELEVATE 12 study. The drug is an oral selective sphingosine 1-phosphatase (S1P) receptor modulator. It demonstrated statistically significant improvements in clinical remission after 12 weeks, as well as statistically significant improvements in all key secondary endpoints.
Argenx shared positive topline data from its ongoing Phase III ADAPT-SC trial of efgartigimod (Vyvgart) in generalized myasthenia gravis (gMG). It hit the primary endpoint of total IgG reduction from baseline on the 29th day of observation. It is a subcutaneous formulation made with Halozyme’s ENHANZE drug delivery technology recombinant human hyaluronidase PH20.
4D Pharma reported results from its Phase I/II trial of MRx0518 in combination with Merck’s Keytruda (pembrolizumab) in renal cell carcinoma (RCC). They were positive interim results. MRx0518 is made up of orally delivered single strains of bacteria derived from healthy human guts. Keytruda is Merck’s anti-PD-1 checkpoint inhibitor.
NovoCure announced the results of a pre-specified interim analysis of the Phase III INNOVATE-3 trial of Tumor Treating Fields (TTFields) with paclitaxel for platinum-resistant ovarian cancer. The independent DMC recommended the continuation of the trial.
Rezolute announced positive data from its Phase IIb RIZE trial of RZ358 in congenital hyperinsulinism. RZ358 is a human monoclonal antibody that binds to a unique site on insulin receptors in the liver, fat and muscle, counteracting the effects of increased insulin.
PharmaTher announced positive topline data from the dose-finding and tolerability study of ketamine for levodopa-induced dyskinesia in Parkinson’s disease. The results are adequate to give an effective size in powering a Phase III trial.
Pluristem released Phase I results of PLX-R18 in patients with incomplete hematopoietic recovery following hematopoietic cell transplantation (HCT). The drug was well-tolerated, and patients receiving the drug demonstrated an increase in all three blood cell types compared to baseline.
AstraZeneca reported that its Phase III CALLA study of Imfinzi (durvalumab) with chemoradiotherapy (CRT) failed to hit the primary endpoint in locally advanced cervical cancer. The primary endpoint was an improvement in progression-free survival versus CRT alone.
Jazz Pharmaceuticals dosed the first patient in its Phase II EMERGE-201 trial of Zepzelca (lurbinectedin) as a monotherapy in urothelial carcinoma, large cell neuroendocrine carcinoma of the lung and homologous recombination deficient (HRD) tumors. Zepzelca is an alkylating agent that binds guanine receptors within DNA.
Oncolytics Biotech announced that its partner Adlai Nortye advanced to the third and final dose escalation cohort of the bridging clinical trial of pelareorep-paclitaxel combination therapy in Chinese patients with advanced or metastatic breast cancer. Pelareorep is an intravenous immunotherapeutic that induces anti-cancer immune responses and promotes an inflamed tumor phenotype via innate and adaptive immune responses.
MoonLake Immunotherapeutics is proceeding with a global Phase II trial of sonelokimab in moderate-to-severe hidradenitis suppurativa. The drug is an investigational Nanobody designed to treat inflammatory disease by inhibiting IL-17A/A, IL-17A/F, and IL-17F/F dimers that drive inflammation.
Sun Pharmaceutical Industries presented data from two pivotal Phase III trial of Winlevi (clascoterone) cream 1% for topical treatment of acne vulgaris (acne). The results for safety and efficacy were favorable in patients 12 years and older.
Morphic Therapeutic initiated the EMERALD1 Phase IIa trial of MORF-057 in moderate to severe ulcerative colitis. MORF-057 is a potent and selective oral small molecule inhibitor of the alpha 4 beta 7 integrin.
LEO Pharma announced up to 3.5-year data that further support the long-term safety and efficacy of Adbry (tralokinumab-ldrm) in adults with moderate-to-severe atopic dermatitis (AD). Adbry is a high-affinity human monoclonal antibody to IL-13.
Nimbus Therapeutics presented data from the Phase Ib trial of NDI-034858 in moderate-to-severe plaque psoriasis. The drug is an investigational oral allosteric tyrosine kinase 2 (TYK2) inhibitor. The data indicated improvement across multiple measures of disease pathology.
Dermavant Sciences presented new data from the Phase III PSOARING 3 long-term extension study of tapinarof cream for plaque psoriasis in adults. Tapinarof is a novel, non-steroidal, once-daily therapeutic aryl hydrocarbon receptor modulating agent.
Arcutis Biotherapeutics announced new pooled results from the DERMIS Phase III trials of roflumilast cream for plaque psoriasis. Roflumilast is a selective and highly potent phosphodiesterase-4 inhibitor.