Clinical Catch-Up: November 16-20
Although there was quite a bit of clinical trial news overall, the biggest focus was on COVID-19 vaccines, with the three leaders in the U.S. and Europe—Moderna, Pfizer and BioNTech, and AstraZeneca and the University of Oxford—all presenting clinical trial news. Here’s a look.
COVID-19-Related
Moderna reported interim efficacy data for its COVID-19 vaccine of 94.5%. The primary endpoint of the trial was based on analysis of COVID-19-positive cases confirmed two weeks after the second vaccine dose. The first interim analysis was built on 95 cases, with 90 cases of positive COVID-19 in the placebo group compared to five cases seen in the vaccinated group.
The secondary endpoint looked at severe cases of COVID-19 and included 11 severe cases in the interim data analysis. All 11 were in the placebo group, zero in the vaccine group. There was a diverse mix of patients in the positive COVID-19 cases, including 15 people aged 65 and older, 20 from diverse communities, including 12 Hispanic or LatinX, four Black or African Americans, three Asian Americans, and one multiracial.
Pfizer and BioNTech announced they had completed their Phase III trial of their COVID-19 vaccine candidate, BNT162b2. This comes only a week after announcing interim data from the trial suggesting a 90% efficacy rate for the vaccine. The more comprehensive data suggests a 95% efficacy rate.
In addition to coming sooner than expected, the results are even better than expected. The trial hit all primary efficacy endpoints. The first primary objective analysis is based on 170 cases of COVID-19, with 162 cases seen in the placebo group compared to eight cases in the cohort receiving the vaccine. They found efficacy consistent across all age, gender, race and ethnicities, and the efficacy in older adults over 65 years of age was more than 94%.
AstraZeneca and the University of Oxford published Phase II clinical trial results for their COVID-19 vaccine in The Lancet. The data shows the vaccine is safe and offers a similar immune response in all adults. The vaccine, dubbed ChAdOx1 nCoV-19, stimulated a T-cell response within 14 days of the initial dose and an antibody response within 28 days of the second dose. Although still not certain, researchers believe the T-cell responses will be needed for long-term immunity against the SARS-CoV-2 virus that causes COVID-19.
BioAegis Therapeutics expanded its clinical trial of recombinant human plasma gelsolin (rhu-pGSN) for severe COVID-19. The trial was begun in Augustin, Spain. It is expanding it in additional sites in Europe.
PTC Therapeutics initiated a Phase II/III trial of pTC299 for treatment of COVID-19. The drug is a dihydroorotate dehydrogenase (DHODH) inhibitor.
RedHill Biopharma’s RHB-107 (upamostat) was approved for a Phase II/III trial in patients with symptomatic COVID-19 who do not require hospitalization. RHB-107 is a first-in-class, oral inhibitor of several serine proteases, and has demonstrated antiviral and possible tissue-protective effects.
CytoDyn filed a protocol with the FDA for a Phase II trial of leronlimab for COVID-19 patients suffering from “long-hauler” symptoms. Leronlimab is a humanized IgG4 monoclonal antibody that blocks CCR5.
Organicell Regenerative Medicine began enrolling patients at an additional site, Larkin Hospital North in Hialeah, Florida, for its Phase I/II trial of Zofin for COVID-19. Specifically, an IV transfusion of the drug is being evaluated for treatment of moderate to severe acute respiratory syndrome (SARS) related to COVID-19. Zofin is an acellular biologic derived from perinatal sources and manufactured to retain naturally occurring microRNAs.
Sinovac Biotech reported that its CoronaVac COVID-19 vaccine caused a fast immune response, but the level of antibodies was below that seen in recovered patients. The results were published in The Lancet Infectious Diseases and came from Phase I and II trials in China of more than 700 volunteers.
Boehringer Ingelheim and the Icahn School of Medicine at Mount Sinai enrolled the first patient in a trial of nintedanib in adults patients having acute lung injury after COVID-19 infection. The trial, ENDCOV-I will study the development and course of pulmonary fibrosis in 120 patients receiving nintedanib or placebo who have acute lung injury secondary to COVID-19, and who required invasive or noninvasive respiratory support. Nintedanib is approved in the U.S. for IPF as Ofev, and to slow the rate of decline in pulmonary function in patients with SSc-ILD, and to treat chronic fibrosing ILDs with a progressive phenotype.
Non-COVID-19-Related
Gilead Sciences and Novo Nordisk presented data from a Phase II proof-of-concept clinical trial of semaglutide in combinations with cilofexor and/or firsocostat in non-alcoholic steatohepatitis (NASH). The trial had five arms that evaluated combinations of Novo Nordisk’s semaglutide, a GLP-1 receptor agonist with Gilead’s FXR agonist cilofexor and/or Gilead’s ACC inhibitor firsocostat over 24 weeks. The trial hit its primary endpoint. It demonstrated that in people with NASH and mild to moderate fibrosis, all combinations were well tolerated. There were also exploratory endpoints that evaluated biomarkers of liver health at 24 weeks in post-hoc analysis. These showed statistically significant improvements in hepatic steatosis, as measured by MRI proton density fat fraction (MRK-PDFF) and liver injury, as measured by serum alanine aminotransferase (ALT). This was in the combination arms compared to semaglutide alone.
Glympse Bio announced first-in-human clinical data from its Phase I trial supporting the safety of the company’s biosensors from a gene expression study of patients with advanced fibrosis in NASH. The novel injectable mixture of synthetic sensors measured the activity of proteases associated with NASH.
Atara Biotherapeutics presented 15-month safety and efficacy data from the two highest dose cohorts of the Phase I OLE trial of ATA188 in progressive forms of multiple sclerosis. ATA-188 is an off-the-shelf mixture of engineered T-cells to target Epstein-Barr Virus (EBV)-infected B cells and plasma cells in the CNS.
Cerevance announced positive results from a Phase Ib trial of CVN-58 for cognitive impairment associated with schizophrenia (CIAS). CVN058 is a brain-penetrant, small-molecule antagonist of the type 3 receptor for serotonin.
Precigen dosed the first patients with UltraCAR-T cells manufactured using the UltraPorator system. They were dosed with PRGN-3005 UltraCAR-T cells in the intraperitoneal arm of the ongoing Phase I trial for advanced ovarian cancer patients.
Biohaven Pharmaceuticals and Weill Cornell Medicine plan to initiate a proof-of-concept trial with the company’s CGRP Receptor Antagonist in plaque psoriasis. The company’s CGRP-receptor antagonist platform includes Nurtec ODT (Rimegepant) and zavagepant.
Takeda Pharmaceutical is advancing mezagitamab (TAK-079) into a Phase II trial for generalized myasthenia gravis (MG). Mezagitamab is an anti-CD38 antibody. Takeda and XOMA entered into a collaboration deal to identify possible antibodies in 2006.
BeyondSpring announced positive topline data from its PROTECTIVE-2 Phase III trial of plinabulin in combination with pegfilgrastim in preventing chemotherapy-induced neutropenia. The trial demonstrated statistically significant improvement in the rate of prevention of Grade 4 neutropenia in Cycle 1, as well as hitting statistical significance in all key secondary endpoints, including duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir.
Intravacc announced results from its experimental vaccine against Shigella, intestinal bacteria that cause severe diarrhea and dysentery. The vaccine was well tolerated and immunogenic.
Genenta Science presented new preliminary clinical data from a Phase I/IIa trial of Temferon in patients with glioblastoma multiforme (GBM). Temferon is based on ex-vivo gene transfer into autologous hematopoietic stem-progenitor cells (HSPCs) to deliver immunomodulatory molecule directly via tumor-infiltrating monocytes/macrophages.
EyePoint Pharmaceuticals announced positive data for Yutiq and Dexycu, demonstrating significant efficacy results from the second Phase III trial of Yutiq and significant inflammatory reduction post-cataract surgery from a retrospective real-world data study of Dexycu. The presented the data at the American Academy of Ophthalmology (AAO) 2020 Virtual Annual Meeting.
The Janssen Pharmaceutical Companies of Johnson & Johnson presented new 12-month data from the ongoing Phase I/II trial of its investigational gene therapy for inherited retinal disease X-linked retinitis pigmentosa (XLRP). Low and intermediate doses were well-tolerated and continued to show statistically significant sustained or increased vision improvement. The gene therapy was jointly developed with Meira GTx holdings.
Karyopharm Therapeutics announced results of the Phase III BOSTON trial of Xpovio in r/r multiple myeloma. Xpovio is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound, evaluated in combination with once-weekly Velcade (bortezomib) and low-doses dexamethasone against standard twice weekly Velcade in adults with MM who had received one to three previous lines of therapy.
PTC Therapeutics initiated a Phase I trial of PTC518 in healthy patients. The therapy was identified from the company’s splicing platform and is being developed to treat Huntington’s disease. PTC518 is an oral molecule with broad central nervous system and systemic distribution. It targets Huntingtin protein expression.
Rigel Pharmaceuticals finalized the design of its FORWARD Phase III trial of fostamatinib disodium hexahydrate in warm autoimmune hemolytic anemia (AIHA). The drug, with the brand name Tavalisse, is already indicated for treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. AIHA is a rare, serious blood disorder where the immune system produces antibodies that attack the body’s red blood cells.
CymaBay Therapeutics presented positive results from the ENHANCE Phase III trial of seladelpar for primary biliary cholangitis (PBC). The data suggests the drug is well positioned to be a preferred second-line therapy for PBC. Seladelpar is a potent, selective, orally active PPARδ agonist.
Helixmith enrolled the first patient in its Phase III trial of engensis (VM202) for diabetic peripheral neuropathy. Engensis is a gene therapy based on plasmid DNA. In addition to diabetic peripheral neuropathy, it is being evaluated for diabetic foot ulcers, claudication, ALS, coronary artery disease and Charcot-Marie-Tooth disease.
PureTech Health announced the completion of its Phase I multiple ascending dose and food effect study of LYT-100 (deupirfenidone). It showed favorable proof-of-concept for the drug’s tolerability and pharmacokinetic (PK) profile. LYT-100 is a deuterated, oral small molecule designed to overcome the challenges of pirfenidone, an approved anti-inflammatory and anti-fibrotic drug. Pirfenidone is currently indicated for idiopathic pulmonary fibrosis (IPF) but has significant tolerability issues and dose-limiting toxicities.
AZTherapies announced completion of the last patient/last visit in its COGNITE Phase III trial of ALZT-OP1 for Alzheimer’s disease. ALZT-OP1 is a proprietary combination of two previously approved small molecules that have been redesigned and formulatized for rapid pulmonary uptake and crossing of the blood-brain barrier. The drug is designed to shift activated microglia from a pro-inflammatory state to a neuroprotective state in order to reduce neuroinflammation.
Chiasma announced positive topline data from its Phase III MPOWERED non-inferiority trial comparing MYCAPSSA (oral ocreotide capsules) to long-acting injectable somatostatin analogs (SSAs) for maintenance of biochemical response in patients with acromegaly. MYCAPSSA is currently approved in the U.S. for long-term maintenance in acromegaly patients who responded to and tolerated treatment with injectable ocretoide or lanreotide.
Gemoscience Pharma completed the Phase Ib trial of GNS561 in primary and secondary liver cancer patients. It plans to begin Phase II trials in 2021. The data from the Phase Ib identified a recommended dose and appeared safe in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) that is not appropriate for curative therapy, in patients with locally advanced metastatic intrahepatic cholangiocarcinoma (iCCA), in patients with pancreatic adenocarcinoma (PDAC) and liver metastasis, and in patients with colorectal cancer (CRC) and liver metastasis. GNS561 is a PPT-1 inhibitor that blocks autophagy.
Cellectis announced that the FDA had lifted the clinical hold on its Phase I MELANI-01 trial of UCARTCS1 for patients with r/r multiple myeloma. Patient enrollment is ongoing in two other Phase I trials, AMELI-01 evaluating UCART123 in r/r acute myeloid leukemia and BALLI-01 of UCART22 in r/r B-cell acute lymphoblastic leukemia. UCARTCS1 is an allogeneic, off-the-shelf, gene-edited T-cell product designed to treat CS1/SLAMF7-expressing hematologic malignancies.
Hepion Pharmaceuticals announced an independent Data Safety Monitoring Board had approved continuation of its Phase IIa AMBITION trial of CRV431 in nonalcoholic steatohepatitis (NASH). The study will now enroll NASH patients in the 225 mg dose cohort.
Adaptimmune Therapeutics presented durability of response data from patients with synovial sarcoma from the Phase I ADP-A2M4 clinical trial. ADP-A2M4 is an engineered TCR T-cell product. There was a mean duration of response of 28 weeks; 7 of 16 patients had confirmed partial responses, with disease control in 15 patients.
Ocuphire Pharma enrolled the first patient in its MIRA-2 Phase III trial of Nyxol to reverse pharmacologically-induced mydriasis. Mydriasis is dilation of the pupil. Nyxol is a proprietary and stable eye drop formulation of phentolamine mesylate.
Sequana Medical announced positive interim data from the first 13 patients in the Roll-In Cohort of the North American pivotal POSEIDON trial of the alfapump for recurrent or refractory ascites due to liver cirrhosis. The data show positive outcomes against all primary endpoints. The alfapump is a fully-implanted, programmable, wireless, CE-marked device that automatically pumps ascites from the peritoneal cavity into the bladder, where the body eliminates them in the urine.
ZIOPHARM Oncology presented new clinical data from three ongoing clinical trials of Ad-RTS-hIL-12 plus veledimex for the treatment of recurrent glioblastoma and diffuse intrinsic pontine glioma. The data on combining the drugs demonstrated a subset of patients with rGBM that showed very encouraging survival at 16 months.
Urovant Sciences announced positive efficacy and safety data from the EMPOWUR long-term extension study of fibegron over a total exposure of 52 weeks. The data suggested the drug improved quality of life and incontinence efficacy endpoints with good long-term tolerability in adults with overactive bladder and symptoms of urge urinary incontinence, urgency and urinary frequency. The drug is a once-daily, beta-3 adrenergic agonist.
Intraop Medical and the University of Verona (Italy) enrolled the first patient in the PancFORT Phase II trial of primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma. The primary endpoint is three-year disease-specific survival.
RedHill Biopharma initiated its Phase III trial of RHB-204 as a potential first-line, standalone, oral treatment of pulmonary nontuberculous mycobacteria (NTM) disease. There is no FDA-approved first-line therapy. RHB-204 is a fixed-dose oral capsule containing a combination of clarithromycin, rifabutin, and clofazimine.
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