Clinical Catch-Up: June 7-11
A busy week for clinical trial news as the American Society of Clinical Oncology (ASCO) meeting wrapped up and the European Hematology Association (EHA) 2021 Virtual Congress began. Read on for more.
RedHill Biopharma completed enrollment and randomized the final patient in its Phase II/III trial of Yeliva (opaganib) in patients hospitalized with severe COVID-19 pneumonia. Opaganib is a proprietary, first-in-class, oral sphingosine kinase-2 (SK2) selective inhibitor with dual anti-inflammatory and antiviral activity.
AzurRx BioPharma dosed the first patient in the Phase II RESERVOIR trial of FW-1022 for COVID-19-related gastrointestinal infections. FW-1022 is an oral formulation of micronized niclosamide.
Inovio announced it was expanding a previously announced partnership with Advaccine Biopharmaceuticals Suzhou to run the Phase III part of a Phase II/II INNOVATE trial of INO-4800. INO-4800 is Inovio’s two-dose COVID-19 vaccine.
SpringWorks Therapeutics and Seagen are planning a Phase I trial of SpringWork’s gamma secretase inhibitor in combination with Seagen’s SEA-BCMA, a monoclonal antibody targeting B-cell maturation agent (BCMA) in patients with r/r multiple myeloma. The trial is expected to start in the second half of this year.
SALVAT completed the Phase III clinical trials in the U.S. for its new ophthalmic corticosteroid nanoemulsion for ocular inflammation and pain after cataract surgery. Final results are expected early in the second half of 2021 with submission to regulators by the end of the year.
Cullinan Oncology received the go-ahead from the FDA to run a Phase I trial of CLN-049 for r/r acute myeloid leukemia (AML). The drug is a FLT3 x CD3 bispecific antibody.
Merck and Eisai announced new investigational from the pivotal Phase III CLEAR/KEYNOTE-581 trial that studied the combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) plus everolimus compared to sunitinib for first-line treatment of advanced renal cell carcinoma (RCC). Keytruda is a checkpoint inhibitor. Lenvima is an orally available multiple receptor tyrosine kinase inhibitor. Everolimus is an immunosuppressant to prevent rejection of organ transplants and for the treatment of renal cell cancer. It is an mTOR inhibitor. Sunitinib is a multi-targeted receptor tyrosine kinase (RTK) inhibitor.
BeyondSpring presented three abstracts on data from the PROTECTIVE-2 Phase III program of plinabulin in combination with pegfilgrastim for prevention of chemotherapy-induced neutropenia (CIN). Plinabulin is a novel, IV-infused, selective immunomodulating microtubule-binding agent (SIMBA).
AnHeart Therapeutics Co. and Innovent Biologics presented preliminary results from the Phase II TRUST trial of taletrectinib in patients with ROS1 fusion positive non-small cell lung cancer. In the crizotinib treatment-naïve patients the overall response rate (ORR) was 93% and the disease control rate (DCR) was 93%. Talectrectinib is a next-generation tyrosine kinase inhibitor (TKI) that targets ROS1 and NTRK fusion mutations.
BlueRock Therapeutics and Asklepios BioPharmaceutical, both Bayer subsidiaries, dosed the first patient in a Phase I study of DA01 for Parkinson’s disease. DA01 is a pluripotent stem cell-derived dopaminergic neuron gene therapy.
G1 Therapeutics presented data from its Phase I trial of rintodestrant. Rintodestrant is an oral selective receptor degrader (SERD) and is being tested in combination with palbociclib for treatment of ER+/HER2- advanced breast cancer. Encouraging antitumor activity was observed with no additional toxicities.
Janssen Oncology, a Johnson & Johnson company, presented data on overall survival from the Phase III MAIA trial of Darzalex in multiple myeloma and the first data from the Phase III GLOW trial of fixed-duration treatment with Imbruvica plus venetoclax compared to chlorambucil plus obinutuzumab in previously untreated elderly or younger unfit patients with CLL/SLL. It is the first Phase III trial to show the positive clinical profile of fixed-duration I+V in first-line CLL.
Arena Pharmaceuticals randomized the first participant in its Phase II trial of IV temanogrel for treatment of coronary microvascular obstruction (cMVO) in patients undergoing percutaneous coronary intervention (PCI). The drug is a peripherally acting and selective 5-HT2A receptor inverse agonist. The Phase II trial is being run in the U.S., Australia, Sweden, Netherlands, and UK.
Chinook Therapeutics presented data from its ongoing Phase I/II trial of BION-1301 in patients with IgAN. IgA Nephropathy (IgAN) is an autoimmune disease that attacks the kidneys. BION-1301 is a novel anti-APRIL monoclonal antibody and blocking APRIL is a possible disease-modifying approach to treating IgAN by decreasing circulating levels of galactose-deficient IgAA1 (Gd-IgA1).
PDS Biotechnology Corporation presented interim data from the Phase II trial led by the National Cancer Institutes’ (NCI) of PDS0101 (Versamune-HPV16) in combination with bintrafusp alfa and NHS-IL12. Versamune induces large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ T-cells. Bintrafusp alfa is a bifunctional “trap” fusion protein targeting TGF-beta and PD-L1. NHS-IL12 is a tumor-targeting immunocytokine. In the study so far, tumor reduction was observed in 83% of HPV16-positive r/r checkpoint inhibitor-naïve advanced cancer patients and 58% of HPV16-positive r/r advanced cancer patients who have also failed checkpoint inhibitor therapy.
BeyondSpring presented data on its Phase III PROTECTIVE-2 chemotherapy-induced neutropenia (CIN) study on its plinabulin in combination with pegfilgrastim in breast cancer. Plinabulin is a selective immunomodulating microtubule-binding agent (SIMBA). The combination demonstrated a superior immune profile and CIN prevention outcomes compared to pegfilgrastim alone in breast cancer patients who received TAC (Taxotere, doxorubicin, and cyclophosphamide). It also presented data from the PROTECTIVE-1 Phase III trial of plinabulin for prevention of CIN.
Vaccinex activated the first clinical sites to screen and enroll participants in its Phase I/II study of pepinemab as a single agent in Alzheimer’s disease and in its Phase II trial of the drug in combination with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) as frontline treatment for advanced, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Pepinemab is a SEMA4D inhibitor. SEMA4D is highly expressed in head and neck cancer and triggers increased levels of myeloid-derived suppressor cells that inhibit immune responses to tumors. Inhibition of SEMA4D also appears to have a unique mechanism of action that reduces activation of inflammatory glial cells in the brain while increasing immune infiltration and altering the balance of cytotoxic and immunosuppressive cells in a tumor microenvironment.
Oxurion completed patient enrollment in Part A of its two-part Phase II KALAHARI trial of multiple injections of THR-149 for the treatment of diabetic macular edema (DME). THR-149 is being developed for DME patients who don’t respond to anti-VEGF therapy. It acts by inhibiting the plasma kallikrein-kinin system, a VEGF-independent target for DME.
Anavex Life Sciences exceeded its enrollment target for ANAVEX 2-73 (blarcamesine) Phase IIb/III trial in Alzheimer’s disease. It expects topline results by mid-2022. Anavex 2-73 is an oral, small-molecule activator of the sigma-1 receptor (SIGMAR1).
HOOKIPA Pharma presented positive Phase I data from its ongoing Phase I/II trial of HB-200 for advanced Human Papillomavirus 16+ cancers. Preliminary data show the therapy is highly immunogenic, including high levels of activated, tumor antigen-specific CD8+ cells.
Avadel Pharmaceuticals announced new post hoc analysis of data from the completed pivotal Phase III REST-ON trial of FT218 for patients with narcolepsy. The drug is currently under review at the FDA with an October 15, 2021 PDUFA date. The new data showed the once-nightly formulation of sodium oxybate taken at bedtime was effective in addressing symptoms of narcolepsy without the patient having to wake up in the middle of the night.
eFFECTOR Therapeutics dosed the first patient in its Phase IIb trial of tomivosertib in combination with Merck’s Keytruda (pembrolizumab) for non-small cell lung cancer (NSCLC). Tomivosertib is a highly selective translation regulation inhibitor that targets MNK1 and MNK2, which appears to enhance killing of tumor cells by T-cells, delays T-cell exhaustion and improves T-cell central memory pool.
Outlook Therapeutics administered the first dose to the last patient enrolled in its pivotal NORSE TWO trial of ONS-5010 (bevacizumab-vikg) for wet age-related macular degeneration. Topline data is expected in the third quarter of 2021. ONS-5010 is a full-length, humanized anti-VEGF recombinant monoclonal antibody that inhibits VEGF and associated angiogenic activity.
Lyra Therapeutics announced successful outcomes from an End-of-Phase II meeting with the FDA for LYR-210 for chronic rhinosinusitis (CRS). They established key elements of the Phase III program for the drug’s 505(b)(2) new drug application, with a single primary endpoint of improvement at week 24 using a composite score of three cardinal symptoms of CRS: nasal blockage, nasal discharge, and facial pain.
Novartis announced results from the pivotal Phase III RATIONALE 302 trial of its investigational anti-PD-1 immune checkpoint inhibitor tislelizumab. The trial demonstrated improved overall survival (OS) compared to chemotherapy in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy. Tislelizumab was engineered to minimize binding to macrophage Fc-gamma receptors, a potential mechanism of anti-PD-1 resistance.
MediWound completed patient enrollment for interim assessment of its EscharEx U.S. Phase II study for the treatment of venous leg ulcers. EscharEx is a bioactive therapy for debridement of chronic and other hard-to-heal wounds.
AlzeCure Pharma presented data from the Phase Ib trial of ACD440 for pain. ACD440 is a TRPV1 antagonist and there were no topical or systemic adverse events reported. It also had a highly significant analgesic effect on both laser-evoked pain and mechanical sensitivity.
Viewpoint Molecular Targeting initiated patient enrollment and screening for its Phase I trial of VMT01 for metastatic melanoma. This is an imaging study. It will enroll 10 subjects with Stage III/IV unresectable melanoma. It uses information guided by a low-risk medical imaging scan, and a treatment plan with the VMT01 ligand is designed to deliver alpha-particle radiation specifically to melanoma tumors.
89bio initiated the ENLIVEN Phase IIb trial of BIO89-100 for patients with fibrosis stage 2 or 3 non-alcoholic steatohepatitis (NASH). BIO89-100 is a specifically engineered glycoPEGylated analog of FGF21.
Acer Therapeutics, after a Type B meeting with the FDA, is now planning a pivotal trial of Edsivo (celiprolol) in patients with COL3A1+ vascular Ehlers-Danlos Syndrome (vEDS). vEDS is an inherited disorder caused by mutations in the genes responsible for collagen. It is a spectrum disorder with a wide variety of forms, the most serious of which is vEDS, generally caused by a mutation in the COLD3A1 gene, which causes abnormal fragility in blood vessels.
HiberCell initiated a Phase Ia trial of HC-5404-FU for selected metastatic tumors. The drug is an endoplasmic reticulum stress modulator. It is specifically looking at patients that include renal cell carcinoma, gastric cancer, breast cancer, and small-cell lung cancer.
Aligos Therapeutics presented data from the ongoing Study ALG-000184-201, which describes the initial safety, pharmacokinetics, and antiviral activity of daily oral doses of ALG-000184 in healthy volunteers and Chronic Hepatitis B (CHB) patients who were treatment-naïve or currently not treated. It also demonstrated a mean reduction in hepatitis B virus DNA.
The University of Texas MD Anderson Cancer Center published results from the single-institution Phase II trial of ibrutinib and venetoclax, which demonstrated lasting disease remission in patients with newly diagnosed chronic lymphocytic leukemia (CLL). It represents the longest follow-up data on patients receiving that particular drug combination.
Valneva completed recruitment for the clinical lot-to-lot consistency Phase III trial of its single-shot chikungunya vaccine, VLA1553. The study will involve 410 people 18 to 45 years of age and they will be followed for six months. The goal is to show manufacturing consistency of the vaccine by demonstrating that three consecutively manufactured lots create equivalent immune responses measured by neutralizing antibody titers on Day 29 after vaccination. Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV). Mortality is low, but morbidity is high. Symptoms include fever, debilitating joint and muscle pain, headache, nausea, rash and chronic arthralgia.
Adamas Pharmaceuticals published new data from two Phase III trials of Gocovri (amantadine) in Parkinson’s disease and dyskinesia. The data was mostly on improvements in motor activities, such as freezing, tremor and getting out of bed/car/deep chair. The data suggested the drug may meaningfully decrease the impact of Parkinson’s disease symptoms on experiences of daily living.
BeiGene presented long-term follow-up results from three pivotal trials at the 26th European Hematology Association 2021 (EHA2021) Virtual Congress. In the case of teslilizumab, they presented 34-month follow-up results from a Phase II trial that showed the drug was active and generally well-tolerated in R/R cHL. In the case of Brukinsa, they presented 35-month follow-up data from a Phase II trial showing the drug’s long-term benefit and tolerability for patients with R/R MCL. They also presented 34-month follow-up data from a pivotal Phase II trial. Brukinsa continued to show deep and durable responses in patients with R/R CLL, regardless of subgroup characteristics. It was well-tolerated with no new safety issues. BeiGene also presented data from the interim analysis of the Phase III ALPINE trial comparing Brukinsa to Imbruvica (ibrutinib). The Phase III ALPINE trial demonstrated superiority, the primary endpoint, of investigator-assessed overall response rate (ORR) and superiority in a key secondary endpoint of atrial fibrillation or flutter.
Bristol Myers Squibb and Acceleron Pharma presented a first look at data from the Phase II BEYOND trial of Reblozyl (luspatercept-aamt) in non-transfusion dependent (NTD) beta thalassemia. It showed that 77.7% of patients receiving Reblozyl achieved a hemoglobin increase compared to 0% of patients in the placebo group. Reblozyl is an erythroid maturation agent.
Sanofi presented data from the Phase III CADENZA study of sutimlimab for cold agglutinin disease (CAD). It reinforced previous data from the 2019 CARDINAL study.
Equillium presented data from the Phase Ib EQUATE trial of itolizumab and standard of care in first-line acute graft-versus-host-disease (aGVHD). The data demonstrated that itolizumab gave a complete response and overall response rate of 55% and 7-%, respectively. Overall survival at month six across all doses was 67%. Itolizumab is a first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM pathway.
bluebird bio presented multiple studies of Zyntelgo (betibeglogene autotemcel, beti-cel), its gene therapy for transfusion-dependent β-thalassemia (TDT). The data continues to demonstrate that patients receiving the therapy can be free of the need for transfusions and maintain strong Hb levels over multiple years.
Vertex Pharmaceuticals announced that VX-864 led to a statistically significant increase from baseline in plasma functional AAT levels compared to placebo in a Phase II trial in alpha-1 antitrypsin deficiency (AATD) with the PiZZ genotype. Although the data provided proof-of-mechanism, the company reported the magnitude of efficacy in the trial wasn’t likely to result in substantial clinical benefit, and is not planning to take it into a Phase III trial. The company, along with CRISPR Therapeutics, also presented new data on 22 patients, with at least 3 months follow-up, treated with CRISPR/Cas9-based gene-editing therapy, CTX001 for TDT and severe sickle cell disease. The data showed a consistent and sustained response.
PTC Therapeutics announced positive interim results from the ongoing RAINBOWFISH trial demonstrating that pre-symptomatic infants with spinal muscular atrophy (SMA) receiving Evrysdi reached motor milestones such as sitting without support, rolling, crawling, standing unaided and walking independently. Also data from a 12-month interim analysis of the JEWLFISH trial demonstrated overall stabilization in motor function and rapid and sustained increases in SMN protein. Patients receiving Evrysdi followed other treatments, including Spinraza or Zolgensma.
ORYZON Genomics presented positive efficacy data from its ongoing Phase IIa ALICE trial of iadademstat in combination with azacytidine in elderly or unfit patients with acute myeloid leukemia. The evidence, they said, continues to be robust and consistent with previous data, with an ORR of 83%.
Autolus Therapeutics presented data related to AUTO1 (obecabtagene autoleucel, obe-cel) in r/r indolent B-cell lymphomas. They also gave an update on duration of response in r/r adult ALL. The therapy achieved 100% CR in a cohort of r/r indolent B-cell lymphomas. And durability of response in ALL patients continues to support the potential of the drug.
Mustang Bio updated interim data from the ongoing Phase I/II trial of MB-106, a CD20-targeted, autologous CAR-T therapy for high-risk B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia. In the 15 patients treated, the ORR was 93% with a CR rate of 67%.