clinical study

It was a fairly busy week with clinical trial updates and announcements. Here’s a look.

COVID-19-Related

Moderna announced it had finalized the Phase III clinical trial structure for its COVID-19 vaccine, mRNA-1273. The Phase III trial will enroll about 30,000 participants in the U.S. They will be randomized 1:1 to receive either a placebo or the vaccine. The primary endpoint of the trial will be prevention of symptomatic COVID-19 disease, with key secondary endpoints including prevention of severe COVID-19, defined as hospitalization, and prevention of infection by SARS-CoV-2.

The 100-microgram dosage was chosen as the optimal dose level based on data from the Phase I trial. The company indicates it has manufactured enough vaccine to begin the Phase III trial. With the dosage finalized at 100 micrograms, it believes it could deliver about 500 million doses annually, and potentially up to 1 billion doses pear year starting in 2021 between its internal U.S. manufacturing site and its collaboration with Switzerland-based Lonza.

Eli Lilly and Company announced that its partner Junshi Biosciences had dosed the first healthy volunteer in a clinical trial of a neutralizing antibody against COVID-19. The company is testing a second antibody to test and is conducting preclinical studies of a third antibody. In an interview with Reuters, the company’s Chief Scientific Officer Daniel Skovronsky said the third antibody could possibly begin human trials in the next few weeks. But the statement that got everyone more excited was when he indicated one of the antibodies might be available for use by September.

Relief Therapeutics and NeuroRx have expanded their Phase II/III clinical trial of RLF-100 for COVID-19 to include patients receiving high flow oxygen and noninvasive ventilation (CPCP), in addition to patients on ventilators. RLF-100 (Aviptadil) is a formulation of synthetic human Vasoactive Intestinal Peptide (VIP).

AstraZeneca reported that its Calquence (acalabrutinib) decreased markers of inflammation and improved clinical outcomes of Severe COVID-19 patients. The study was of 19 hospitalized patients with COVID-19 and severe hypoxia and/orinflammation. Calquence is a Bruton’s tyrosine kinase (BTK) inhibitor. It is approved in the US for certain hematological cancers.

Junshi Biosciences dosed the first healthy volunteer in the Phase I trial of JS016 at Huashan Hospital Affiliated to Fudan University in China. JS016 is the first SARS-CV2 neutralizing antibody to enter clinical trials in China. Junshi and Eli Lilly and Company are collaborating to co-develop JS016 globally.

CytoDyn hit its 75 patient enrollment target for its Phase II trial of leronlimab for mild to moderate COVID-19. Leronlimab is a humanized IgG4 monoclonal antibody that blocks CCR5 and was first developed for HIV.

Non-COVID-19-Related

Alnylam Pharmaceuticals released positive Phase III data from the ILLUMINATE-A clinical trial of lumasiran in the treatment of primary hyperoxaluria type 1 (PH1). PH1 is an ultra-rare disease of the kidneys and urinary tract that can results in painful and recurrent kidney stones and nephrocalcinosis. Lumasiran is the company’s experimental RNA interference (RNAi) therapy that targets hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO), so by silencing HAO1 and depleting the GO enzyme, the drug blocks production of oxalate.

In the study, lumasiran hit the primary endpoint with a 53.5% mean reduction in urinary oxalate compared to placebo. It also demonstrated a 65.4% mean reduction in urinary oxalate relative to baseline.

Astellas Pharma released the results from the Phase III DOLOMITES trial comparing its roxadustat with Amgen’s Aranesp (darbepoetin alfa) for anemia in non-dialysis dependent (NDD) adults with stage 3-5 chronic kidney disease (CKD). Roxadustat is a first-in-class oral inhibitor of hypoxia-inductible factor (HIF) prolyl hydroxylase (PH). Roxadustat was non-inferior to Aranesp in hemoglobin levels during the first 24 weeks of treatment, which was the trial’s primary endpoint.

Aimmune Therapeutics announced new two-year data suggesting long-term efficacy of daily treatment with Palforzia in patients with peanut allergy. This data is from a follow-on study from the Phase III PALISADE trial. Palforzia is an oral immunotherapy of concentrated peanut protein.

Sarepta Therapeutics announced positive results from a study of SRP-9003, its gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). The data included safety and expression results from three trial participants in the high-dose cohort at 60 days and one-year functional data from three trial participants in the low-dose cohort. SRP-9003 is being developed for LGMD2E, a monogenic neuromuscular disease caused by a lack of beta-sarcoglycan (beta-SG) proteins.

Axovant Gene Therapies completed enrollment in the low-dose cohort of the Phase I/II trial for Type II GM1. AXO-AAV-GM1 is a gene therapy that delivers a functional copy of the GLB1 gene via an AAV vector with the goal of restoring beta-galactosidase enzyme activity. GM1 gangliosidosis is a progressive and fatal pediatric lysosomal storage disorder.

Quantum Leap Healthcare Collaborative announced an evaluation of SAR439859, an oral estrogen receptor degrader (SERD) in a new I-SPY 2 study arm targeting patients with newly diagnosed HR+ stage 2/3 invasive breast cancer. The EOP study will use an oral SERD as the endocrine therapy backbone. Sanofi’s SAR439859 has been chosen as the oral SERD for the trial.

Neurocrine Biosciences announced positive data from its competed Phase II trial of crinecerfont in classic congenital adrenal hyperplasia (CAH). CAH is a genetic disorder affecting the adrenal glands. Crinecerfont is a novel, potent, selective, oral, non-steroidal corticotropin-releasing factor type 1 (CRF1) receptor antagonist.

CSL Behring announced results from a Phase II clinical trial of garadacimab (formerly CSL312), an investigational novel Factor XIIa-inhibitory monoclonal antibody to prevent hereditary angioedema (HAE). The company presented results at the European Academy of Allergy and Immunology (EAACI) Digital Congress 2020.

The trial met the primary endpoint, showing decreased number of attacks compared to placebo in patients with HAE. HAE is a rare, genetic and potentially life-threatening disease. HAE is one of two types of bradykinin-mediated angioedema, with the other being nonhereditary or acquired angioedema. HAE is the result of deficient or dysfunctional C1-INH, a blood protein that helps control inflammation.

Sarepta Therapeutics announced positive results from a small study of SRP-9003, its gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). This is a type of muscular dystrophy that affects both males and females. The data included safety and expression results from three clinical trial participants in the high-dose cohort measured at 60 days, as well as one-year functional data from three participants in the low-dose cohort. SRP-9003 is a “gene construct” that delivers a gene that codes for the full-length beta-sarcoglycan protein. It is the absence of this protein that results in LGMD2E.

Dermavant Sciences completed enrollment in the long-term safety part of a Phase III program of tapinarof in adults with plaque psoriasis. The program includes PSOARING 1 and 2, two identical Phase III trials—91% of patients who completed the trials have enrolled in the long-term safety study. Tapinarof is a potential first-in-class, once-daily topical therapeutic aryl hydrocarbon receptor modulating agent (TAMA).

Biogen announced new data from the NURTURE trial of pre-symptomatic patients with spinal muscular atrophy (SMA). SMA is a rare, autosomal recessive neuromuscular disease characterized by the degeneration of alpha motor neurons in the spinal cord. This results in progressive muscle weakness and paralysis. According to the Orphanet Journal of Rare Diseases, the estimated incidence is 1 in 6,000 to 1 in 10,000 live births. In the NURTURE study to date, Biogen found that in babies genetically diagnosed with SMA, early and sustained treatment with Spinraza for up to 4.8 years allowed “unprecedented survival.” The patients continued to maintain and progress gains of motor function compared to the natural course of the illness.

Denali Therapeutics and its development partner Sanofi announced data from its Phase Ib trial of DNL747 in Alzheimer’s disease and amyotrophic lateral sclerosis (ALS). After apparent disappointing results, the companies have chosen to pause the studies with the drug and shift their resources to a similar drug, DNL788, for the same indications. In 31 patients in two 29-day Phase Ib studies in Alzheimer’s disease and ALS, and additional data from six ALS patients in an open label extension trial, they found that DNL747 was safe and well tolerated at the dose being evaluated. However, in parallel toxicity studies in monkeys, the drug showed dose- and duration-dependent adverse results at higher levels. The companies indicate the findings were off-target and molecule-specific, but nonetheless would make it difficult and potentially dangerous to increase the doses of the drug in humans to get better effects without additional clinical safety studies.

Merck announced that its checkpoint inhibitor Keytruda (pembrolizumab) did not meet its pre-specified dual primary endpoints in a study of the drug in combination with chemotherapy for the first-line treatment of advanced or metastatic urothelial carcinoma, a type of bladder cancer. The dual primary endpoints were overall survival (OS) or progression-free survival (PFS), compared with standard of care chemotherapy. Although the final analysis of the Phase III KEYNOTE-361 trial showed a numerical improvement in OS and PFS, the data did not meet statistical significance per the pre-specified statistical plan.

InspireMD published the 12-month PARADIGM trial results, which described its MicroNET embolic prevention stent system used for consecutive symptomatic and increased stroke-risk asymptomatic carotid stenosis revascularization. In 101 unselected consecutive patents enrolled in the trial, at 30 days, only one adverse event occurred, and no strokes occurred between 30 days and 12 months.

Catalyst Biosciences completed its Phase I MMA-102 trial for Marzeptacog alfa (activated). The data showed the use of SQ MarzAA to treat episodic bleeding for hemophilia A or B patients. The company indicates it is on schedule to enroll the first patient in its Phase III trial in 2020.

NeuSpera Medical completed the first chronic clinical implants of the Neuspera Neuromodulation System on the sacral nerve. The ultra-miniaturized device is being tested in the recently launched SANS-UUI two-stage pivotal trial for patients with Urinary Urgency Incontinence (UUI).

Pfizer announced positive topline data from the Phase III JADE TEEN trial of abrocitinib in moderate to severe atopic dermatitis (AD) in patients ages 12 to 18 years. Abrocitinib is an oral, once-daily Janus kinase 1 (JAK1) inhibitor. The patients were also on a background topical therapy. Both doses of the drug met the co-primary endpoints and were generally well tolerated.

INmune Bio got the go-ahead in the UK to launch a Phase I trial of INKmune, a novel therapy to prime a patient’s own NK cells to attack their cancer. The trial will be in high-risk myelodysplastic syndrome. INKmune is a suspension of replication incompetent tumor cells from the company’s proprietary tumor cell line, INB16.

Impel NeuroPharma announced positive results from STOP 301, its pivotal Phase III trial of INP104 (dihydroergotamine mesylate, or DHE) administered to the vascular rich upper nasal space via Impel’s POD technology for acute migraine. The trial met its primary objectives, with no new safety signals or concerning trends.

Partner Therapeutics enrolled the first patient dosed in a Phase II trial of Leukine (sargramostim, rhu-GM-CSF) in T-cell release HLA-mismatched haploidentical stem cell transplant recipients who are receiving post-transplant cyclophosphamide. Leukine is a recombinant human granulocyte-macrophage growth factor that stimulates the differentiation, maturation and mobilization of cells involved in the innate and adaptive immune response.

Bluebird bio presented data from a Phase I/II trial of LentiGlobin in adults with sickle cell disease. The data showed a near-complete reduction of serious vaso-occlusive crises (VOCs) and acute chest syndrome (ACS).

CRISPR Therapeutics with Vertex Pharmaceuticals presented new clinical data for CTX001, a gene therapy, from the CLIMB-111 and CLIMB-121 Phase I/II trials in transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease, respectively. The CLIMB-111 data demonstrated clinical proof-of-concept in the first patient dosed. In CLIMB-121, the data showed that nine months after CGX001 infusion, the patient was free of VOCs, transfusion independent and had improved hemoglobin levels.

ADC Therapeutics updated data from its pivotal Phase II trial of loncastuximab tesirine (Lonca) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It also presented interim data from its Phase I/II trial of Lonca in combination with ibrutinib. In the LOTIS 2 study, Lonca showed anti-tumor activity and durability in difficult-to-treat patients with r/r DLBCL.

Apellis Pharmaceuticals presented data from its Phase III PEGASUS trial that showed superiority for pegcetacoplan over eculizumab in hemoglobin levels in adults with paroxysmal nocturnal hemoglobuinuria (PNH). The company plans to submit an NDG to the FDA and MAA to EMA in the second half of this year.

Takeda Oncology presented positive data from two studies of Ninlaro, an oral proteasome inhibitor in multiple myeloma. The Phase III TOURMALINE-MM4 trial showed treatment with Ninlaro resulted in a statistically significant and clinically meaningful improvement in PFS.

Verrica Pharmaceuticals presented new pooled data from two analyses of its Phase III CAMP trials of VP-102 (cantharidin 0.7% topical solution) for molluscum contagiosum. The drug showed statistically significantly higher percentage of patients with complete clearance of all baseline and new lesions compared to vehicle.

Genentech and Roche presented new data on the Port Delivery System with ranibizumab (PDS), a new anti-HtrA1 molecule for geographic atrophy and data from the companies’ Personalized Healthcare program. The PDS data was part of the Ladder Phase II trial, which was used to address vitreous hemorrhage complicated. The Phase I trial of anti-HtrA1 was in wet acute macular degeneration (AMND).

ORYZON presented new efficacy data from its ongoing Phase II ALICE trial of iadademstat in combination with azacytidine in elderly patients with acute myeloid leukemia. The data was robust and consistent with previous data, noting an ORR of 77% and of those, 60% were complete remissions and 40% partial remissions.



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