SCB-01A

Spine BioPharma's lead drug for chronic low back pain (CLBP) didn't succeed in a Phase III trial, with the company blaming an unexpectedly strong placebo effect at some sites for masking the treatment's true impact.The MODEL trial tested SB-01 (vicatertide) — a TGF-β antagonist delivered via intradiscal injection — in 417 patients in the US with degenerative disc disease (DDD). To be counted as a success, patients had to show both a two-point drop on a 10-point pain intensity numerical rating scale (NRS) and a 15-point gain on the Oswestry Disability Index (ODI).While the drug showed "numerical and clinically meaningful improvement" in pain intensity and pain-related function, it failed to meet the study's primary composite endpoint (ODI+NRS) at six months, the company said. According to topline results released Friday, 67% of SB-01 recipients met the threshold, but the difference from the sham group wasn't significant. Among the 281 patients who completed the 12-month follow-up, 62% of those treated with SB-01 achieved composite success.High sham control response"We are surprised by the very high sham control response," said Fran Magee, chief technical officer. While SB-01 recipients responded "as anticipated" in the study, Magee said the sham control response was far higher than in the company's Phase II trial, or what's typically seen in CLBP studies.Further, the sham response wasn't uniform, according to the company, which said "statistically reliable evidence" showed wide variation across study sites. At locations where the placebo effect aligned with earlier data (n=227), the company said 70% of SB-01 patients hit the primary endpoint versus 59% in the sham group, a nominally significant result."This was a landmark, well-designed clinical trial with strict enrollment criteria and very high follow-up rates," remarked principal investigator Christopher Gilligan. "Pain studies are challenging and are susceptible to a sham control response, which was particularly high in this study."Spine BioPharma says it plans to meet with the FDA to explore possible next steps and whether prior Phase I and II data can be factored into a potential path to approval. SB-01, also known as YH14618, was previously developed by Yuhan and licensed to Spine BioPharma in 2018.

Senior Female Scientist Works with High Tech Equipment in a Modern Laboratory. Her Colleagues are Working Beside Her. gorodenkoff/Getty Images/iStockphoto Achilles dosed the first patient in a Phase I/IIa advanced NSCLC trial, Logic Bio’s pediatric methylmalonic acidemia study is back up and running and another look at Roche’s TIGIT flop. It was another busy week for clinical trial news, with approvals, trial data, clinical holds and more. Continue reading for a look at the latest updates. COVID-19-Related Moleculin Biotech received approval from UK regulators to proceed with a first-in-human Phase Ia trial of WP1122 in healthy volunteers for treatment of COVID-19. The drug is a metabolism/glycosylation inhibitor, a prodrug of a well-known glucose decoy, 2-deoxy-D-glucose (2-DG). Non-COVID-19-Related AC Immune published data from its Phase Ib study of ACI-24 in Down syndrome. ACI-24 is an anti-Abeta vaccine. It was found to be safe and elicited an immune response. Achilles Therapeutics dosed the first patient with personalized clonal neoantigen-reactive T cells (cNeT) manufactured using the company’s higher-dose VELOS Process 2. The Phase I/IIa CHIRON trial is evaluating the drug in advanced non-small cell lung cancer (NSCLC). It also initiated enrollment in Cohort B of the THETIS trial of cNeT in combination with a PD-1 checkpoint inhibitor for metastatic malignant melanoma. LogicBio Therapeutics received the go-ahead from the FDA to continue dosing its Phase I/II Sunrise trial. The agency placed a clinical hold on the study after a severe adverse event was observed in four pediatric patients, two requiring hospitalization for thrombotic microangiopathy (TMA). The study is evaluating LB-001 in methylmalonic acidemia (MMA). LB-001 uses homologous recombination to edit a patient’s genome, giving them a non-mutated version of the MMUT gene. Athira Pharma extended the duration of its open-label study of fosgonimeton for mild-to-moderate Alzheimer’s disease. It has tripled in length, from six months to 18 months. Fosgonimeton is a small molecule that enhances the activity of hepatocyte growth factor (HGF) and its receptor, MET. The HGF-MET pathway is involved in neuronal growth and survival. LianBio completed a Phase I PK study of mavacamten in healthy Chinese volunteers. The study was parallel with the ongoing Phase III EXPLORER-CN study of mavacamten in obstructive hypertrophic cardiomyopathy. Mavacamten (Camzyos) is the first and only cardiac myosin inhibitor approved by the FDA for adults with symptomatic class II-III obstructive hypertrophic cardiomyopathy. Elpiscience Biopharma received the green light from the FDA to initiate a Phase I trial of ES014 in advanced solid tumors. E014 is a first-in-class anti-CD39xTGF-beta bispecific antibody that simultaneously targets the CD39-adenosine and TGF-beta pathways. Imago Biosciences dosed the first patient in the Phase I/II trial of bomedemstat in combination with Genentech’s Tecentriq (atezolizumab) during the maintenance phase of treatment in people with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC). Bomedemstat is a lysine-specific demethylase 1 (LSD1) inhibitor. Tecentriq is an anti-PD-1/PD-L1 checkpoint inhibitor. Zenith Epigenetics initiated a Phase II trial of ZEN-3694 with Pfizer’s Talzenna (talazoparib) for triple-negative breast cancer. Talzenna is a PARP inhibitor. ZEN-3694 blocks the expression of the MYC gene to prevent cellular growth in certain types of tumors. PsioloTec Health Solutions , operating as Zylorion Health, received approval from the Health Research Ethics Board of Alberta (Canada) to run a Phase II trial in patients with treatment-resistant depression. The first group will receive intranasal esketamine (Spravato), while the second group will receive Spravato and Zylorion’s multi-modal therapy, Almond Therapy. Neogene Therapeutics received the go-ahead from the Dutch regulatory authority for a Phase I trial of NT-125 for advanced solid tumors. NT-125 is an autologous, fully-individualized, multi-specific TCR therapy. Theratechnologies initiated enrollment in the basket portion of the first-in-human trial of TH1902 for sortilin-expressing cancers. TH1902 is a peptide drug conjugate (PDC), which conjugates the company’s proprietary peptide with other anti-cancer agents, such as docetaxel. Faraday Pharmaceuticals enrolled the first patient in its Iocyte AMI-3 Phase III trial of FDY-5301 in reducing cardiovascular death and heart failure in anterior ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous intervention (PCI). FDY-5301 is an elemental reducing agent containing sodium iodide. Synthetic Biologics announced positive safety data from its Phase I trial of SYN-020. SYN-020 is an intestinal alkaline phosphatase (IAP) potentially being developed to treat celiac disease, nonalcoholic fatty liver disease (NAFLD), and radiation enteropathy, as well as possible metabolic and inflammatory disorders associated with aging. ABVC Biopharma dosed the first patient at the Cheng Hsin General Hospital in Taiwan of its Phase II part 2 trial of ABV-1505 for Attention-Deficit Hyperactivity Disorder. Part 1 was successfully completed at the University of California, San Francisco. CARsgen Therapeutics reported data from an investigator-led Phase I trial of CT041 for treatment of hematologic malignancies and solid tumors were published. CT041 is a CAR-T-cell candidate for solid tumors. Genentech , a Roche company, reported that its Phase III Skyscraper-01 trial failed to meet its co-primary endpoint of progression-free survival (PFS). However, the other co-primary endpoint, overall survival (OS), was immature at the first analysis, and the trial will continue until the next planned analysis. The study is evaluating tiragolumab, an anti-TIGIT immunotherapy, plus the company’s anti-PD-L1 checkpoint inhibitor Tecentriq (atezolizumab) compared to Tecentriq alone as first-line treatment for people with PD-L1-high locally advanced or metastatic non-small cell lung cancer (NSCLC). Numerical improvement was observed for both PFS and OS. The drug combination appears to be well-tolerated with no new safety signals when adding tiragolumab. AstraZeneca and Sanofi reported positive data from a Phase III and Phase IIb trial of nirsevimab for the prevention of lower respiratory tract infections caused by infection by the respiratory syncytial virus (RSV). The data demonstrated 79.5% efficacy. Nirvesimab is a monoclonal antibody. AbbVie announced positive topline results from the Phase III U-ENDURE maintenance study of Rinvoq (upadacitinib) in adults with moderate to severe Crohn’s disease who had an inadequate response or were intolerant to conventional or biologic therapy. The data showed patients receiving 15mg or 30mg once daily of upadacitinib achieved the co-primary endpoints of endoscopic response and clinical remission. Glyscend Therapeutics completed the Phase I trial of GLY-200 for type 2 diabetes. GLY-200 is a proprietary mucin-complexing polymer (MCP) that enhances the natural mucus barrier in the duodenum. Intercept Pharmaceuticals dosed the first patient in a Phase II trial of obeticholic acid (OCA) and bezafibrate (BZF) for primary biliary cholangitis (PBC) patients who have not achieved an adequate biochemical response to ursodeoxycholic acid. Myeloid Therapeutics dosed the first patient in the Phase I/II IMAGINE trial of MT-101 in patients with r/r peripheral T cell lymphoma (PTCL). MT-101 is the first mRNA engineered CAR monocyte derived from the company’s ATAK platform. MT-101 targets CD5. Spine BioPharma received the greenlight from the FDA to launch a Phase III trial of SB-01 for Injection for patients with degenerative disc disease. SB-01 is a 7-amino acid peptide that binds to and antagonizes TGF beta1 activity. Medicenna Therapeutics presented clinical data from the Phase I/II ABILITY trial of MDNA11. MDNA11 is a next-generation IL-2 with superior CD122 binding without CD25 affinity. It is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. NervGen Pharma received approval to advance to the third and highest dose cohort in the multiple ascending dose (MAD) portion of its Phase I trial of NVG-291. NVG-291 is a therapeutic peptide that mimics the intracellular domain of the receptor protein tyrosine phosphatase sigma, a cell surface receptor that interacts with chondroitin sulfate proteoglycans. It has shown efficacy in animal models for spinal cord injury, peripheral nerve injury, multiple sclerosis and stroke. Vallon Pharmaceuticals reported additional data from the SEAL study of the abuse potential of its ADAIR, the company’s proprietary abuse-deterrent formulation of immediate release dextroamphetamine in development for attention deficit hyperactivity disorder (ADHD) and narcolepsy. They now have full data and PK data that demonstrated a blunted PK pro to crushed and snorted dextroamphetamine. NRx Pharmaceuticals enrolled the first patient in a Phase II trial of bipolar depression with sub-acute suicidality. They will evaluate NRX-101, an oral, fixed-dose combination of D-cycloserine and lurasidone. Formosa Pharmaceuticals and AimMax Therapeutics reported successful topline data from CPN-301, the first of two Phase III trials of APP13007 for inflammation and pain after cataract surgery. The drug is a novel ophthalmic nanosuspension formulation of a potent corticosteroid, clobetasol propionate (0.05%). Lipocine announced positive topline results from its OLD study of LPCN 1144 for nonalcoholic steatohepatitis (NASH). LPCN 1144 is an orally delivered prodrug of testosterone. NGM Bio initiated a Phase I/Ib trial of NGM438 for advanced solid tumors. NGM438 is a LAIR1 antagonist antibody.