Clinical Catch-Up: September 9-13

clinical study

Last week was a busy one for clinical trial results, particularly with the European Committee for Treatment and Research in Multiple Sclerosis (ECTIRMS) 2019 Congress going on. Here’s a look at some of the top clinical trial stories.

Eli Lilly released data from LOXO-292, which was being investigated in the LIBRETTO-001 clinical trial. LIBRETTO-001 is a Phase I/II clinical trial. The Phase I is a dose escalation phase and the Phase II is a dose expansion phase. The primary endpoint of Phase II was overall response rate (ORR). Secondary endpoints were duration of response (DOR), progression free survival (PFS) and safety.

LOXO-292 (selpercatinib) is being evaluated as a monotherapy for the treatment of RET fusion-positive non-small cell lung cancer (NSCLC). In the registration dataset made up of the first 105 patients with RET fusion-positive NSCLC with previous platinum-based chemotherapy, the drug showed a 68% ORR. The patient group was heavily pretreated with a median of three previous systemic treatments—55% were treated with a checkpoint inhibitor and 48% received at least one multikinase inhibitor. The ORR was similar no matter which therapy they received previously.

Amgen reported good but not amazing results in an early-stage trial of AMG 510 in patients with previously treated KRAS G12C-mutated solid tumors. The new data was a follow-up in a larger cohort of patients. It included a subset of 34 NSCLC patients with 23 being evaluable for efficacy. Thirteen of the patients received the target dose of 960 mg per day, and of them, seven had a partial response at one or more timepoints and six showed stable disease, which gave a disease control rate of 100%.

Neurotrope announced that its Phase II trial of Bryostatin-1 in moderate to severe Alzheimer’s disease did not show statistical significance on the primary endpoint, change from baseline to Week 13 in the Severe Impairment Battery (SIB) total score. The Phase II trial was designed to evaluate the safety and efficacy of the drug for cognitive deficits in patients with moderate to severe Alzheimer’s. This was defined as a Mini Mental State Exam 2 score of 4 to 15 and patients not currently taking memantine. The patients with randomized 1:1 to receive either 20 micrograms of Bryostatin-1 or placebo, receiving seven doses for 12 weeks.

Patients who had received memantine (Namenda XR, Namenda, Namenda Titration Pak) were excluded unless they had stopped taking the drug for at least 30 days before enrollment. An average increase in SIB totals of 1.3 points were observed in the Bryostatin-1 cohort and 2.1 points for the placebo groups at Week 13. The change was not statistically significant.

Janssen Pharmaceutical, Johnson & Johnson companies, announced positive results from two Phase III clinical trials (ASPIRE I and II) of Spravato (esketamine) CIII nasal spray with comprehensive standard of care in adults with major depressive disorder who have active suicidal ideation with intent. Both trials met their respective primary efficacy endpoint, reduction in depressive symptoms at 24 hours after the first dose. The drug in both studies showed clinically meaningful and statistically significant superiority over placebo plus standard of care in rapidly decreasing symptoms of major depressive disorder.

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ACADIA Pharmaceuticals announced its Phase III HARMONY trial evaluating pimavanserin for dementia-related psychosis met its primary endpoint, showing highly statistically significant longer time to relapse of psychosis with the drug compared to placebo. It was part of a planned interim efficacy analysis. The independent data monitoring committee recommend the study be stopped early based on hitting pre-specified stopping criteria.

Novartis reported that a five-year open-label study of Aimovig (erenumab) in patients with episodic migraine showed patients who continued the treatment had at least a 50% decrease in monthly migraine days. Also, 33% of the patients who continued treatment hit a 100% reduction and a 56% achieved a 75% reduction. This was a 4.5-year interim analysis of the five-year study.

Later in the week, the company presented new data on Mayzent (siponimod), additional post hoc analyses from the Phase III EXPAND clinical trial. It showed the drug helped MS patients keep their mobility for over four years longer on average and it significantly decreased grey matter volume loss at one and two years. The drug may have re-myelination properties.

And in what was a busy week, Novartis also presented positive results from the Phase III ASCLEPIOS I and II studies at ECTRIMS. Both studies showed ofatumumab was superior to Aubagio (teriflunomide) in patients with relapsing forms of MS. The two studies are identical. The primary endpoints were whether the drug showed a highly significant and clinically meaningful reduction in the number of confirmed relapses.

Zosano Pharma presented data from a one-year long-term safety study of Qtrypta for the acute treatment of migraine. The study evaluated the safety of a 3.8 mg dose of intracutaneous zolmitriptan in adults with migraine who historically had at least two migraine attacks per month. In one oral presentation at the 19th Congress of the International Headache Society (IHC), they reported pain freedom for 44% of the attacks and freedom from the most bothersome symptoms for 62% after two hours. This was consistent with positive clinical results observed in the Phase II/III pivotal study.

Tyme released encouraging data from a Phase II trial on SM-88 (racemetyrosine) in patients with metastatic pancreatic cancer. The trial is evaluating 49 heavily pretreated patients with radiographically progressive metastatic pancreatic cancer who has significant disease-related morbidity before receiving SM-88. Of the 49 patients, 38 were evaluable for efficacy. As of April 25, 2019, the median overall survival of evaluable patients was 6.4 months, with some efficacy indicators correlating with greater OS.

ORYZON Genomics presented preliminary data from its Phase II CLEPSIDRA trial of iadademstat in combination with standard-of-care (SOC) in relapsing small cell lung cancer (SCLC). The data suggested that the combination of the drug with SOC during the first six cycles resulted in a tumor reduction of 78.7%. The drug appeared to be safe and well tolerated. As monotherapy, reduction of main lesions and metastasis continued, hitting an overall tumor reduction of 86.3% according to CT scans in Cycle 8.

Applied Molecular Transport dosed the first patient in its Phase Ib trial of AMT-101 in ulcerative colitis. The company plans to complete enrollment by the end of the year. AMT-101 is an oral gut-selective biologic fusion protein of interleukin 10 (IL-10). The trial is a multi-center, double-blind, placebo-controlled trial conducted at four centers in Europe.

Biohaven Pharma presented expanded data and post-hoc analyses from its long-term trial of rimegepant on migraine-specific disability and quality of life. More than 1,700 patients with migraine were enrolled in the study. They received 75 mg of rimegepant as needed up to once daily for acute migraine. The new analyses showed improvement in migraine-related disability that were clinically important and statistically significant at all time points.

The company also announced it had completed enrollment in its Phase II/III trial of intranasally administered vazegepant for acute treatment of migraine. Vazegepant is a novel, structurally unique, third-generation calcitonin gene-related peptide receptor antagonist. The trial is designed to evaluate efficacy on regulatory endpoints for acute treatment of migraine.

Bristol-Myers Squibb released the pooled efficacy and safety results from its Phase III CheckMate -017 and CheckMate -057 trials in patients with previously treated advanced non-small cell lung cancer (NSCLC). The results of the two long-term trials showed that patients receiving the company’s checkpoint inhibitor, Opdivo (nivolumab), had a long-term overall survival (OS) improvement compared to docetaxel chemotherapy alone. For the Opdivo group, OS rates at five years were 13.4% compared to 2.6% for docetaxel. The benefit was seen in all subgroups of patients.

AVEO Oncology announced results from the second prespecified analysis of overall survival (OS) in the TIVO-3 Phase III trial of Fotivda (tivozanib) compared to sorafenib in highly refractory metastatic renal cell carcinoma (RCC). The OS hazard ratio was below 1.00, which favored tivozanib. The company indicates that the data suggests the potential of the drug to be an important new treatment option for advanced RCC patients.

ORYZON Genomics presented new positive efficacy data on its central nervous system (CNS) epigenetic drug vafidemstat in autism spectrum disorder (ASD). The data was from the REIMAGINE Phase IIa clinical trial. The third REIMAGINE cohort met the primary endpoint, showing significant global improvements on the Clinical Global Impression (CGI) of Severity (CGI-S) and Improvement (CGI-I) scales, focused on aggressive behavior, as well as significant global improvement on the Neuropsychiatric Inventory (NPI) total score.

VBI Vaccines is collaborating with GlaxoSmithKline to clinically evaluate the combination of VBI-1901, VBI’s cancer vaccine immunotherapeutics, with GSK’s proprietary ASO1B adjuvant system. VBI will add an additional arm to Part B of its Phase I/IIa clinical trial in recurrent glioblastoma (GBM). In Part A, VBI-1901 adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF) was well-tolerated at all doses. And three out of six patients in the high-dose cohort showed evidence of stable disease via MRI, correlating with vaccine-induced immune response.

Momotaro-Gene dosed the first patient in its Phase II trial combining MTG201 with Bristol-Myers Squibb’s checkpoint inhibitor Opdivo in relapsed malignant pleural mesothelioma. MTG201 is a gene therapy that uses the company’s proprietary adenoviral vector tech platform to deliver the Reduced Expression in Immortalized Cells/Dickkopf-3 gene (REIC/Dkk-3) into cancer cells. In cancer, the gene appears to be downregulated, so by introducing the gene, it appears to drive immune reaction to the cancer cells.

Genentech, a Roche company, released full data from its pivotal Phase III SAkuraStar trial of satralizumab as a monotherapy for neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a rare, debilitating autoimmune disease of the central nervous system (CNS) that mostly damages the optic nerve and spinal cord. Satralizumab resulted in a 55% decrease in the risk of relapses compared to placebo in the overall patient population. In a subgroup, which actually made up about 67% of the patient population studied, who were seropositive for AQP4-IgG antibodies, the drug reduced the risk of relapses by 74%. Patients with those antibodies usually experience more severe symptoms.

Ovid Therapeutics randomized its first patient in the Phase III NEPTUNE trial of gaboxadol in Angelman syndrome. The company expects topline data in mid-2020. Gaboxadol is a novel delta-selective GABA-A receptor agonist. Angelman syndrome is a rare genetic disorder characterized by delayed development, intellectual disability, severe speech impairment, seizures, movement and balance problems, sleep disorders and anxiety.

Adverum Biotechnologies presented positive 24-week data from the first cohort of its OPTIC Phase I trial of ADVM-022 in wet age-related macular degeneration (wet AMD). Patients achieved vision maintenance and improvements in retinal anatomy with no anti-VEGF rescue injections needed through week 24. The patients had previously required regular anti-VEGF injections to control the disease. ADVM-022 is a gene therapy that uses a proprietary vector capsid carrying an aflibercept coding sequence.

Quantum Genomics launched a new study of firibastat in patients with renal failure. It expects to begin enrollment in September 2019. Firibastat is a first-in-class brain aminopeptidase A inhibitor (BAPAI). Analysis of the company’s NEW-HOPE Phase IIb trial of the drug in hypertension showed the drug didn’t negatively impact renal function. This trial will confirm that the drug may be used to treat hypertension, particularly in treatment-resistant patients or heart failure, potentially even in patients with associated renal failure.

Atara Biotherapeutics presented initial efficacy data and safety results from its ongoing Phase I trial of ATA188 for progressive forms of MS. ATA188 is an off-the-shelf, allogeneic T-cell immunotherapy targeting Epstein-Barr Virus (EBV)-infected B-cells thought to be associated with MS. The therapy appears to be well tolerated and has encouraging efficacy results so far.

Ritter Pharmaceuticals announced its Phase III trial of RP-G28 for lactose intolerance failed to meet statistical significant in its pre-specified primary endpoint. Ritter focuses on the microbiome, the trillions of microorganisms that inhabit the body, to treat gastrointestinal diseases. In the trial, the treatment group reported a 3.159 mean reduction in lactose intolerance symptoms compared to 3.420 in the placebo group. It also missed its first secondary endpoint of responders with a meaningful treatment benefit.

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