Clinical Catch-Up: December 7-11

Medical Patient

It was an unusually busy week for clinical trial updates, largely because of the annual American Society of Hematology (ASH) meeting from Sunday December 5 through Wednesday December 9. There were also other meetings and the usual corporate updates. Read on for further information.

COVID-19-Related

Novavax and UC Davis Health plan to launch a Phase III clinical trial of Novavax’s experimental COVID-19 vaccine. Novavax’s product uses a traditional vaccine technology using a protein subunit from the spike protein of the SARS-CoV-2.

AstraZeneca and the University of Oxford published an interim analysis of their four Phase III clinical trials of AZD1222, their COVID-19 vaccine. The data was published in The Lancet and demonstrated the vaccine is safe and effective at preventing symptomatic COVID-19. It also protects against severe disease and hospitalization.

The efficacy is 70.4%. The AstraZeneca-Oxford data was partial results from studies in the UK, Brazil and South Africa, with safety data on 23,745 participants and protection levels on 11,636. Complicating the analysis, as reported earlier, a cohort of the trial accidentally received half-doses of the initial shot, and that group demonstrated efficacy up to 90%, which has still not been explained. The broader dosing regimen demonstrated 62% efficacy, with the average analysis demonstrating about 70%. However, the data also suggests the possibility of protection after a single dose. And at least one dosing regimen appears to have decreased the number of asymptomatic infections.

Sorrento Therapeutics received FDA approval to launch a Phase I trial of intravenous STI-2020 (COVI-AMG) in healthy volunteers and outpatient COVID-19 patients with mild symptoms. STI-2020 is a monoclonal antibody engineered for high potency against the virus, with possibly effectiveness against antibody drug-resistant SARS-CoV-2 variants, including the E484K, F4905, Q493R and S494P mutations. The antibody has demonstrated strong binding affinities to the currently dominant D614G variant and the mink-associated N439K variant compared to that for wild-type SARS-CoV-2

Sinopharm, based in China, reported that its COVID-19 vaccine showed 86% efficacy, according to health authorities from the United Arab Emirates (UAE). Sinopharm is a business unit of China National Pharmaceutical Group. The phase III trial launched in the UAE in July. The vaccine was developed from a strain of the virus isolated from a patient in the Jinyintan Hospital in Wuhan, China, cultivated in a qualified Vero cell line for propagation, and the supernatant of the infected cells was inactivated with B-propiolactone. The study in the UAE included 31,000 volunteers across 125 nationalities.

AstraZeneca, which is jointly developing a COVID-19 vaccine with the University of Oxford, plans to begin clinical trials testing its vaccine in combination with Russia’s Sputnik V vaccine by the end of the year. The Russian vaccine was developed by the country’s National Research Center for Epidemiology and Microbiology and the Gamaleya Center.

GlaxoSmithKline and Sanofi reported that their COVID-19 vaccine probably will not be ready until late 2021 because in trials to date, provided “insufficient” immune response in older adults. In adults 18 to 49, the vaccine’s immune response was comparable to convalescent COVID-19 patients’ immune levels.

Non-COVID-19-Related

CRISPR Therapeutics and Vertex Pharmaceuticals presented new data on 10 patients treated with CTX001, which demonstrated a consistent and sustained response, in transfusion-dependent beta thalassemia (TDT) and sickle cell disease (SCD). CTX001 is an investigational CRISPR/Cas9-based gene-editing therapy.

Fate Therapeutics presented a patient case study from its Phase I trial of FT596. FT596 is a universal, off-the-shelf, CD19-targeted CAR natural killer (NK) cell product candidate. The patient was heavily pre-treated for diffuse large B-cell lymphoma (CLBCL).

Janssen Pharmaceutical of Johnson & Johnson announced longer-term data from the combined Phase Ib/II CARTITUDE-1 trial evaluating ciltacabtagene autoleucel (cilta-cel) for r/r multiple myeloma. Cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy.

Janssen also announced results from pooled analyses of long-term follow-up from multiple clinical trials of Imbruvica (ibrutinib) monotherapy and in combination as first-line treatment for CLL/SLL with high-risk features.

Autolus Therapeutics announced new data highlighting progress of its AUTO1 program in r/r adult B-Acute Lymphocytic Leukemia (ALL). The program is the company’s CAR-T cell therapy currently in the ALLCAR Phase I trial.

Poseida Therapeutics reported results from an ongoing Phase I trial of P-BCMA-101 in r/r multiple myeloma. P-BCMA-101 is an autologous CAR-T product candidate.

AbbVie and Genentech presented extended follow-up data from the Phase III MURANO and CLL14 clinical trial of Venclexta (venetoclax) fixed duration treatment combinations. The data presented supported the use of the drug in first-line or previously treated chronic lymphocytic leukemia (CLL).

AbbVie also presented new data from the Phase II CAPTIVATE trial of Imbruvica (brutinib) in combination with Venclexta in CLL/SLL patients. The data showed the combination provided continued disease-free survival for CLL patients once treatment was complete.

Bristol Myers Squibb and bluebird bio updated data of the company’s BCMA directed CAR-T therapy idecabtagene vicleucel (ide-cel). The data included longer-term updated results from the original Phase I CRB-401 trial in r/r multiple myeloma, including the primary endpoint of safety and exploratory endpoints of progression-free survival (PFS) and overall survival (OS).

Syros Pharmaceuticals announced new clinical data from its Phase II trial of SY-1425 in two acute myeloid leukemia (AML) patient populations. SY-1425 is a first-in-class selective retinoic acid receptor alpha agonist. It is being tested in combination with azacytidine.

Kura Oncology offered preliminary clinical data from KOMET-001, its ongoing Phase I/IIa trial of KO-539 in r/r/ AML. KO-539 is an oral, potent and selective menin inhibitor.

Kite Pharma, a Gilead Sciences company, announced four-year follow-up data from the pivotal ZUMA-1 trial of Yescarta (axicabtagene ciloleucel) in adults with refractory large B-cell lymphoma. Of the 11 patients in the Phase II cohort, Yescarta was administered to 101 patients with r LBCL and the median time from leukapheresis to complete response (CR) was less than two months. There have been no Yescarta-related secondary malignancies reported.

Kite also presented follow-up data from the ZUMA-2 trial of Tecartus (brexucabtagene autoleucel) in adults with r/r mantle cell lymphoma (MCL). At the median follow-up of 17.5 months, 92% achieved a response, including 67% with CR.

Gilead also updated results from the Phase Ib trial of magrolimab in AML patients ineligible for intensive chemotherapy, including patients with TP53-mutant AML. Magrolimab is its potential first-in-class, anti-CD47 monoclonal antibody.

Syndax Pharmaceuticals announced updated data from its Phase I trial of axatilimab in chronic graft versus host disease (cGVHD). Axatilimab is the company’s anti-CSF-1R monoclonal antibody.

Orca Bio announced the first clinical data from its first-generation Orca-T therapy in a Phase I/II trial for cGVHD. The data demonstrated that Orca-T provided faster neutrophil and platelet engraftment, a decreased incidence of grade 2+ acute GvHD and chronic GvHD, and significantly higher one-year GvHD-free and relapse-free survival (GRFS) compared to a cohort of patients receiving standard-of-care hematopoietic stem cell transplant.

TG Therapeutics announced pivotal data from the UNITY-CLL and UNITY-NHL trials. In UNITY-CLL, U2 significantly improved PFS over Obinutuzumab plus chlorambucil as well as ORR in patients with CLL. In UNITY-NHL, umbralisib monotherapy demonstrated ORR of 49.3% in r/r MZL and 45.3% in r/r FL patients.

Incyte announced data from three ongoing Phase II trials of parsaclisib. The drug is a highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta. It is being developed for r/r follicular (CITADEL-203), marginal zone (CITADEL-204) and mantle cell (CITADEL-205) lymphomas. The primary endpoints for all three trials were ORR, DOR, PFS, and OS. All three were promising.

Precigen described clinical progress and new data from the ongoing Phase I/Ib trial of PRGN-3006 UltraCAR-T in r/r AML and higher risk MDS. PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T cell treatment leveraging the company’s non-viral Sleeping Beauty system to simultaneously express a CAR specifically targeting CD33.

Seqirus announced late-breaking data from a systematic review and meta-analysis confirming the benefit of an MF59-adjuvanted trivalent seasonal flu vaccine for adults 65 years and older. The company also presented new data on its adjuvanted, cell-based pandemic influenza A (H5N1) vaccine. Two doses of the vaccine demonstrated a strong immune response in pediatric, adult and older adult patients.

Autolus Therapeutics presented new data on AUTO3, the company’s CD19 and CD22 dual targeting CAR-T product candidate in the ALEXANDER Phase I/II trial in r/r DLBCL. As of October 30, 49 patients in the study were treated and evaluable. AUTO3 was well-tolerated, with low rates of cytokine release syndrome and neurotoxicity.

Takeda Pharmaceutical presented five hematology posters and four abstracts at ASH. Included: ATHN-2, a longitudinal, observational study of previously treated hemophilia patients switching coagulation replacement factor products; Advate, a 6-year interim analysis of the AHEAD International and Germany studies of antihemophilic factor for hemophilia A treated with Advate; Feiba, interim analysis of the FEIBA Global Outcome study (FEIBA GO) of activated prothrombin complex concentrate as prophylaxis or on-demand treatment in patients with congenital hemophilia A or B with inhibitors; two studies on von Willebrand Disease; a retrospective U.S. claims database analysis in patients with sickle cell disease.

Mustang Bio announced interim data from the ongoing Phase I/II trial of MB-106 in r/r B-cell non-Hodgkin lymphoma (NHL). MB-106 is a CD20-targeted, autologous CAR-T cell therapy. It is being developed with Fred Hutchinson Cancer Research Center.

Blueprint Medicines presented data from the Phase I EXPLORER trial of Ayvakit with modified IWG criteria—the ORR was 75% and the rate of complete remission with full or partial hematologic recovery was 36%.

Kronos Bio received FDA go-ahead to launch a Phase I/II trial of KB-0742 in patients with advanced solid tumors in the first quarter of 2021. KB-0742 is a highly selective, orally bioavailable inhibitor of cyclin dependent kinase 9 (CDK9).

Avacen Medical announced the completion and data from the second part of its sponsored 50-person study of glucose tolerance in Type 2 diabetics. The study found a 62 mg/dl reduction in postprandial blood glucose (PBG) after 30 minutes of AVACEN heat and vacuum device use compared to a sham AVACEN device and a heat-only AVACEN device. The AVACEN device is thought to overcome disease-induced microvascular impairment by mechanically recruiting the microvasculature allowing for glucose disposal.

Lyra Therapeutics announced positive results from the LANTERN Phase II trial of LYR-210 for chronic rhinosinusitis (CRS). LYR-210 is designed to deliver up to six months of continuous anti-inflammatory drug therapy to the sinonasal passages for CRS in patients who have not undergone surgery for the disease.

BioSight presented updated clinical data from its ongoing Phase IIb trial of aspacytarabine as a single-agent first-line acute myeloid leukemia therapy for patients who can’t receive standard chemotherapy. Aspacytarabine is ia novel anti-metabolite composed of cytarabine covalently bound to asparagine, acting as a pro-drug of cytarabine.

Oncternal Therapeutics updated interim clinical data from the ongoing Phase I/II CIRLL trial of cirmtuzumab in combination with ibrutinib in mantle cell lymphoma and chronic lymphocytic leukemia. Cirmtuzumab is an investigational anti-ROR1 monoclonal antibody.

Beyond Air began screening patients for its at-home pilot trial of LungFit GO for the treatment of NTM lung disease. The 12-wek trial will run in Australia and enroll about 20 adults with chronic refractory NTM lung disease, enrolling both cystic fibrosis and non-CF patients infected with Mycobacterium avium complex (MAC) or Mycobacterium abscessus complex (MABSC).

ORYZON Genomics presented new positive efficacy data from its ongoing Phase II ALICE trial of iadademstat in combination with azacytidine in elderly AML patients. Iadademstat is a small molecule oral inhibitor of the epigenetic enzyme LSD1.

Catalyst Biosciences presented data from its Phase III CRIMSON 1 study of marzeptacog alfa (activated) to treat on-demand spontaneous or traumatic bleeding episodes in congenital Hemophilia A or B with inhibitors, compared to standard of care. MarzAA is the only SQ delivered therapy for on-demand treatment of bleeding events.

Brickell Biotech dosed the first patient in its second U.S. pivotal Phase III trial of sofpironium bromide gel, 15% in 350 patients ages nine and older with primary axillary (underarm) hyperhidrosis. It is made up of two pivotal trials, Cardigan I and Cardigan II, which are both enrolling patients.

Arcturus Therapeutics began dosing patients with ARCT-810 with ornithine transcarbamylase (OTC) deficiency in a Phase Ib trial.ARCT-810 uses the company’s LUNAR lipid-mediated delivery platform to deliver OTC mRNA to liver cells.

Hookipa Pharma announced positive interim Phase I data for HB-201 for the treatment of HPV16+ cancers. HB-201 is the company’s replicating monotherapy that are designed to express an E7/E6 fusion protein derived from HPV16.

Celyad Oncology announced updates from its CYAD-211 as well as autologous NKG2D receptor-based CAR-T candidates, CYAD-01 and CYAD-02. CYAD-211 is the company’s shRNA-based anti-B cell maturation antigen (BCMA) allogeneic CAR T candidates. They dosed the first patient with CYAD-211 in the IMMUNICY-1 trial. However, they recently released disappointing data from the Phase I THINK trial for CYAD-01, but encouraged by the initial results from CYAD-02 for r/r AML and MDS in the CYCLEL-1 trial.

Karuna Therapeutics presented additional data from its Phase II EMERGENT-1 trial of KarXT in schizophrenia. The data reinforced KarXT’s robust efficacy with statistically and clinically meaningful improvements at primary and key secondary endpoints. The company is on track to initiate a Phase III trial by the end of the year.

Caris Life Sciences announced positive results from validation studies of MI FOLFOXai, its artificial intelligence-based predictor to gauge a metastatic colorectal cancer (mCRC) patient’s likelihood of benefit from first-line treatment FOLFOX followed by FOLFIRI compared to FOLFIRI followed by FOLFOX, both standard of care options. The studies showed the OS of patients consistent with the FOLFOXai prediction was 17 months longer than the OS of patients treated counter to the prediction.

electroCore announced topline data from its GM-US-10 (PREMIUM II) trial of non-invasive vagus nerve stimulation (nVNS) in migraine. The data showed a statistically significant improvement with nVNS compared to sham stimulation.

Harpoon Therapeutics reported on its clinical pipeline: dose escalation continues in Phase I/IIa trial of HPN424 in mCRPC—as of December 1, 69 patients had been dosed across 14 cohorts at fixed doses of 1.3 to 160bng/kg and in step dosing cohorts up to 300ng/kg; the HPN536 (mesothelin TriTAC) Phase I/IIa trial continues dose excalation—across 9 fixed-dose cohort of 6 to 280ng/kg and 1 step dose cohort up to 600ng/kg; dose escalation for HPN217 (BCMA TriTAC) Phase I/II—r/r multiple myeloma patients have been treated across 6 single-patient fixed dose cohorts of 5 to 810 micrograms; and the first patient is expected to be dosed for HPN328 (DLL3 TriTAC) by the end of the year. TriTAC stands for Tri-specific T cell Activating Construct, their technology platform for solid tumors and hematologic malignancies.

Altimmune began dosing in its Phase I single ascending dose (SAD) and multiple ascending dose (MAD) trial of ALT-801. ALT-801 is a long-acting GLP-1/glucagon receptor dual agonist under development for non-alcoholic steatohepatitis (NASH).

Larimar Therapeutics completed dosing in its Phase I SAD trial of CTI-1601 for Friedreich’s ataxia (FA). All doses supported further investigation of CTI-1601, a recombinant fusion protein that delivers human frataxin into the mitochondria of patients with FA who are unable to produce enough of this essential protein.

Orchard Therapeutics reported initial data from its ongoing proof-of-concept clinical trial of OTL-201 in mucopolysaccharidosis type IIA (MPS-IIA, also known as Sanfilippo syndrome type A). OTL-201 is an ex vivo autologous hematopoietic stem cell gene therapy.

Jasper Therapeutics announced clinical data from its ongoing multicenter Phase I clinical trial of JSP191 in patients with severe combined immune deficiency (SCID). JSP191 is a first-in-class anti-CD117 monoclonal antibody. The trial is studying the product as a conditioning agent to enable stem cell transplantation in patients with SCID who are either transplant-naïve or had a previous stem cell transplant with a poor outcome.

AbbVie announced that its Phase III induction study, U-ACHIEVE, of Rinvoq (upadacitinib) in moderate to severe ulcerative colitis, hit the primary endpoint of clinical remission at week 8. It also met all the ranked secondary endpoints. Rinvoq is an oral, once daily, selective and reversible JAK inhibitor. It is approved since August 2019 in adults with moderately to severely active rheumatoid arthritis.

Amylyx Pharmaceuticals presented data from the CENTAUR and OLE trials demonstrating positive results from AMX0035 in the retention of functional abilities and survival for people with ALS. AMX0035 is designed to reduce neuronal death and dysfunction by targeting endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS and other neurodegenerative diseases.

Y-mAbs Therapeutics updated results on Danyelza (naxitamab-gqgk) for r/r high-risk neuroblastoma. In Study 201, a total of 95% of the infusions were administered in an outpatient setting, with a median infusion time of 37 minutes, all completed in less than two hours. The ORR was 68% with 59% CR. In refractory patients, the ORR was 71% with 64% CR, and in relapsed, the ORR was 63% with 50% CR.

Athenex presented updated Phase III PFS and OS data showing the clinical benefits of oral paclitaxel compared to IV paclitaxel in patients with metastatic breast cancer. The data supports previous data suggesting superior efficacy on ORR and favorable tolerability compared to IV paclitaxel.

Prothena reported positive data from the Phase I trial of PRX004 for ATTR amyloidosis. The data showed slowing of neuropathy progression for all seven evaluable patients at nine months. PRX004 is an anti-amyloid immunotherapy designed to deplete amyloid.

Evelo Biosciences reports positive topline data in its Phase Ib trial of EDP1815 in mild to moderate atopic dermatitis. EDP1815 is an oral drug for inflammatory diseases; it is a non-live pharmaceutical preparation of a strain of Prevotella histicola, chosen for its ability to provide systemic pharmacological effects after oral dosing with gut-restricted distribution.

G1 Therapeutics reported final data from its Phase II trial of Trilaciclib in metastatic triple-negative breast cancer (mTNBC). The data showed the drug significantly improved OS for patients receiving the drug in combination with a chemotherapy regimen of gemcitabine/carboplatin (GC) compared with GC alone.

TG Therapeutics announced positive topline results from two global Phase III clinical trials, ULTIMATE I and II, of ublituximab in relapsing forms of multiple sclerosis (RMS). The drug was compared to Sanofi Genzyme’s Aubagio (teriflunomide). Ublituximab is the company’s glycoengineered anti-CD20 monoclonal antibody. Both studies evaluated the safety and efficacy of a one-hour 450mg infusion of ublituximab every six months, following the Day 1 infusion of 150mg over four hours.

City of Hope began recruitment for its Phase I trial of an investigational vaccine that leverages a person’s own immune cells, a beta cell protein and vitamin D3 to potentially treat type 1 diabetes. The vaccine is PLpepTolDC, which was previously evaluated for safety and feasibility in a clinical trial in the Netherlands. In the trial, the vaccine will be developed from the patient’s own dendritic cells, cultured and loaded with vitamin D3 and a fragment of pro-insulin to help train the immune system to reduce inflammation.

Sunovion Pharmaceuticals presented new data and analyses on late-stage compounds SEP-363856 and SEP-4199. SEP-363856 is a trace amine-associated receptor 1 (TAAR1) agonist with serotonin 5-HT1A agonist activity being developed for schizophrenia. SEP-4199 is a non-racemic ratio of amisulpride enantiomers being studied for treatment of major depressive episodes associated with bipolar I disorder.

Clene Nanomedicine presented blinded interim results from the Phase II RESCUE-ALS trial of CNM-Au8 for ALS. CNM-Au8 is an aqueous suspension of clean-surfaced, faceted gold nanocrystals with catalytic activity that can enhance the metabolic energetic capacity of motor neurons while reducing oxidative stress.

PureTech Health initiated a Phase IIa trial of LYT-100 (deupirfenidone) in breast cancer-related, upper limb secondary lymphedema. LYT-100 is a deuterated, oral small molecule designed to overcome the challenges associated with pirfenidone.

BeyondSpring announced new data from its Phase III PROTECTIVE-2 Study 106 demonstrated that plinabulin in combination with pegfilgrastim offers greater protection against chemotherapy-induced neutropenia than standard of care, pegfilgrastim alone. The combination was 53% more effective than pegfilgrastim alone in decreasing the incidence of profound neutropenia.

Spero Therapeutics initiated dosing in patients with nontuberculous mycobacterial pulmonary disease in its dose-ranging Phase IIa trial for SPR720. The drug is an oral antimicrobial agent.

Pharming Group enrolled the first patient in its randomized, open label, parallel group, controlled, pilot clinical trial in 120 patients hospitalized with confirmed COVID-19. The trial will evaluate Ruconest (recombinant human C1 inhibitor) for the prevention of severe COVID-19 infections.

Sanofi announced that they will resume dosing in U.S. clinical trials. They noted that on October 30, they had “voluntarily paused dosing in all ongoing fitusiran clinical studies … to assess reports of non-fatal thrombotic events in patients participating in the Phase III program.” Fitusiran is a once-monthly, subcutaneously dosed non-factor-replacement therapy that leverages small interfering RNA (siRNA) to target and decrease antithrombin. This promotes sufficient thrombin creation to restore hemostasis and prevent bleeding in patients with hemophilia A or B.

They indicate they evaluated the available data and worked with the U.S. Food and Drug Administration (FDA) to get the program back on track. It plans to implement amended trial protocols with an adjusted dosing regimen designed to improve the benefit-risk profile of the drug. This is for the adolescent and adult clinical trials. The pediatric trial is still on hold while they continue to analyze the dosing for that group.

Ultimovacs announced positive five-year OS data from its Phase I trial of UV1, its universal cancer vaccine, in combination with the checkpoint inhibitor ipilimumab in metastatic malignant melanoma. UV1 is a peptide-based vaccine that induces a specific T-cell response against the universal cancer antigen telomerase.

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