Clinical Catch-Up: May 11-15

Clinical Trial Data

Clinical trial updates not related to COVID-19 are on the upswing, partly because some companies are announcing trial information ahead of the upcoming American Society of Clinical Oncology (ASCO) virtual meeting being held at the end of the month. Here’s a look.

In a related note, according to the World Health Organization and ClinicalTrials.gov, there are currently 1,114 ongoing clinical studies of treatments for COVID-19. A GlobalData analysis indicates that so far, 21 of the trials have reported interim results, and out of them, 16 showed positive early results.

COVID-19-Related

Bellerophon Therapeutics’ INOpulse inhaled nitric oxide (iNO) therapy Phase III trial received the go-ahead from the FDA. It will evaluate the therapy in up to 500 COVID-19 patients.

Relief Therapeutics’ U.S. partner NeuroRx filed an IND with the FDA under the Coronavirus Treatment Acceleration Program (CTAP) to run a Phase II/III trial assessing inhaled RLF-100 in patients non-acute lung injury caused by COVID-19. RLF-100 is a formulation of Aviptadil, a synthetic human vasoactive intestinal polypeptide (VIP).

Three-drug antiviral cocktail of AbbVie’s Kaletra (protease inhibitor lopinavir-ritonavir), nucleoside analogue ribavirin, and injectable interferon beta-1b (Bayer’s Betaseron; Novartis’s Extavia), significantly decreased the median time to a negative SARS-CoV-2 test compared to controls in a small Phase II trial. The cocktail appeared to cut the median number of days from 12 days in the control group to seven days. The study was published in The Lancet.

Moderna received fast-track approval from the FDA for mRNA-1273, its COVID-19 vaccine candidate. The approval is for Phase II trials, which the company expects to launch shortly. The Phase II trials will include about 600 healthy volunteers, half between the ages of 18 and 55, with the rest over the age of 55. It hopes Phase III trials will launch this summer.

Relief Therapeutics and NeuroRx announced that NeuroRx had completed final manufacturing of RLF-100 for Phase IIb/III trials to assess IV RLF-100 for Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients on mechanical ventilation. Bachem Americas and MedisourceRx are manufacturing the drug under the supervision of NeuroRx. The University of Miami has begun enrolling patients with Thomas Jefferson University and University of California-Irvine expected to begin soon. Sites at NYU Langone and six other locations in the US will begin enrolling patients by June 2020.

Non-COVID-19-Related

Oyster Point Pharma reported positive topline results from its Phase III ONSET-2 trial in dry eye disease. The primary endpoint was a greater proportion of patients receiving 0.6 mg/ml and 1.2 mg/ml of OC-01 gained greater than or equal to 10 mm on Schirmer’s score, a measure of tear film production, compared to the control group.

OC-01 (varenicline) is a highly selective nicotinic acetylcholine receptor (nAChR) agonist developed as a nasal spray to treat signs and symptoms of dry eye disease (DED). The ONSET-2 Phase III trial was a multicenter, randomized, double-masked, vehicle-controlled study of the safety and efficacy of varenicline for dry eye disease. It enrolled 758 patients at 22 sites in the U.S., evaluating two different doses compared to a control nasal spray. Patients received OC-01 nasal spray twice a day for four weeks.

MyoKardia announced positive topline results from its Phase III pivotal EXPLORER-HCM trial of mavacamten for symptomatic, obstructive hypertrophic cardiomyopathy (HCM). The drug met all primary and secondary endpoints and was well tolerated. The primary endpoint was a composite functional analysis of treatment effective relative to placebo on symptoms and cardiac function. Mavacamten is a novel, oral, allosteric modulator of cardiac myosin.

Protalix Biotherapeutics reported positive topline results from its BRIDGE Phase III open-label, switch-over trial of pegunigalsidase alfa for Fabry Disease. The drug showed substantial improvement in renal function as measured by mean annualized estimated Glomerular Filtration Rate (eGFR slope). Pegunigalsidase alfa (PRX-102) is a plant cell culture-expressed and chemically modified stabilized version of the recombinant alpha-galactosidase-A enzyme.

GENFIT announced that its elafibranor in non-alcoholic steatohepatitis (NASH) failed an interim analysis of the RESOLVE-IT Phase III trial. The company reported that the trial failed to hit the predefined primary endpoint of NASH resolution without fibrosis—scarring—growing worse. The trial evaluated 1,070 patients. Of the 717 patients in the trial who received elafibranor, the response rate was 19.2% compared to 14.7% in the placebo cohort. On the fibrosis key secondary endpoint, the elafibranor cohort, 24% achieved fibrosis improvement of at least one stage compared to 22.4% in the placebo group. Another key secondary endpoint associated with metabolic parameters also failed to achieve statistical significance.

Sanofis Phase III IKEMA trial of Sarclisa (isatuximab) added to carfilzomib and dexamethasone met the primary endpoint at the first planned interim analysis in relapsed multiple myeloma. The drug combo showed significantly prolonged progression-free survival compared to standard of care carfilzomib and dexamethasone alone. No new safety signals were seen.

Pulmonx published data from the LIBERATE Study confirming the effectiveness of the Zephyr Vale in improving shortness of breath, ability to exercise and quality of life for patients with COPD/emphysema. The results were published in the Annals of the American Thoracic Society.

Rocket Pharmaceuticals presented new clinical data on the durability of its gene therapy, RP-L201, for Fanconi Anemia (FA) and Leukocyte Adhesion Deficiency-I (LAD-I) at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT).

Minoryx Therapeutics dosed the first patient in its registration-enabling Phase II NEXUS trial to evaluate the safety and efficacy of leriglitazone in pediatric patients with early-stage cerebral ALD (cALD), the acute form of X-linked adrenoleukodystrophy (X-ALD). Leriglitazone is a novel, brain penetrant, orally bioavailable and selective PPARgamma agonist in late-stage development for severe orphan CNS disorders.

Capricor Therapeutics announced positive topline data from the Phase II HOPE-2 trial of CAP-1002 in patients with advanced Duchenne muscular dystrophy (DMD). The 12-month data showed statistically meaningful improvements in the PUL 2.0 in CAP-1002 treated patients with a mean change of 2.4 points over placebo patients. PUL stands for “performance of the upper limb,” which is a clinically validated measures to evaluate the shoulder, arm and hand strength in patients who are generally non-ambulant. CAP-1002 is an allogeneic “off-the-shelf” cardiosphere-derived cell product.

Merck announced positive data from the Phase III KEYNOTE-355 trial looking at Keytruda in combination with chemotherapy as first-line treatment for metastatic triple-negative breast cancer (mTNBC). In the trial, patients whose tumors expressed PD-L1 with a Combined Positive Score (CPS) greater than or equal to 10, Keytruda with chemotherapy showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS). The drug combination decreased the risk of disease progression or death by 35%, improving PFS to a median of 9.7 months compared to 5.6 months for patients receiving only chemotherapy.

In patients whose cancer expressed PD-L1 with a CPS greater than or equal to 1, the combination improved PFS compared to chemotherapy alone, 7.6 months compared to 5.6 months, but this was not statistically significant.

The company indicates the trial will continue without changes to study the other dual primary endpoint of overall survival (OS).

Genentech, a Roche company, announced positive results from the Phase II CITYSCAPE clinical trial in PD-L1-positive metastatic non-small cell lung cancer (NSCLC). The study was evaluating a new checkpoint inhibitor tiragolumab and its checkpoint inhibitor Tecentriq (atezolizumab) compared to Tecentriq alone.

Tiragolumab is a novel immunotherapy that binds to TIGIT, an immune checkpoint protein found on immune cells. Tecentriq is a PD-L1 checkpoint inhibitor. Both TIGIT and PD-L1 are involved in immune suppression. Blocking both pathways has the potential for improving anti-tumor activity. The two-drug combination hit both co-primary endpoints in the intention-to-treat (ITT) population. It showed improvement in objective response rate (ORR) of 31.3% compared to 16.2%, for the combination compared to Tecentriq alone, respectively. And for progression free survival (PFS), the combo showed a median PFS of 5.4 months compared to 3.6 months for Tecentriq alone.

In patients with high levels of PD-L1, exploratory analysis showed a clinically meaningful improvement in ORR, 55.7% compared to 17.2%, and a 67% decrease in PFS.

Bristol Myers Squibb released new data from two clinical trials of Opdivo plus Yervoy-based combinations in non-small cell lung cancer (NSCLC) and updated results from the KarMMa trial of ide-cel for multiple myeloma being developed with bluebird bio.

For Part 1 of the Phase III CheckMate -227 clinical trial, the company announced three-year follow-up data showing that Opdivo (nivolumab) plus Yervoy (ipilimumab) gave sustained improvements in overall survival (OS) as well as additional efficacy measures as a first-line treatments for metastatic NSCLC. The median follow-up was more than three years—43.1 months—and the combination showed a survival benefit compared to chemotherapy in patients expressing PD-L1 greater than 1%. The three-year OS rates in this population was 33% for the combination compared to 22% for chemotherapy alone.

In the Phase III CheckMate -9LA trial, the company presented first results showing a statistically significant and clinically meaningful survival benefit with Opdivo plus Yervoy, given concomitantly with two cycles of chemotherapy for first-line metastatic NSCLC. The trial met both its primary and key secondary endpoints, showing superior OS, progression-free survival (PFS) and overall response rate (ORR) for the dual immunotherapy plus chemotherapy compared to chemotherapy alone.

For the Phase II KarMMa trial, the two companies presented updated results in patients with relapsed and refractory multiple myeloma (r/r MM). In the trial, 128 patients with heavily pretreated r/r MM who were exposed to at least three previous therapies and were refractory to their last regimen were treated with ide-cel. The overall response rate (ORR) was 73% across all dose levels, including 33% who had a complete response (CR) or stringent CR (sCR). Median duration of response (DoR) was 10.7 months, with 19.0-month median DoR for patients who had a CR or sCR.

Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell immunotherapy.

MorphoSys AG and Incyte updated results from the ongoing Phase II L-MIND trial of tafasitamab and lanlidomide in r/r diffuse large B-cell lymphoma (r/r DLBCL). In the data, 80 patients receiving the two drugs were included in the efficacy analysis. After a minimum of two years’ follow-up, the results are consistent with the primary analysis and confirm the durability of response and overall survival of the combination followed by tafasitamab alone in autologous stem cell transplantation (ASCT)-ineligible patients with r/r/ DLBCL.

Advaxis announced updated clinical and biomarker results from the monotherapy and combination arms of its ongoing Phase I/II trial of ADXS-503 in NSCLC. The trial is evaluating the drug alone and in combination with Merck’s checkpoint inhibitor Keytruda. The trial showed sustained clinical benefit in the combination arm in the first two evaluable patients and in the monotherapy arm, three out of six evaluable patients showed stable disease.

Krystal Biotech announced interim results for a first-in-human Phase I/II trial of KB105 in autosomal recessive congenital ichthyosis (ARCI). The data showed clearly detectable TGM-1 expression in all treated areas and supported a Phase II study. KB1-5 is a replication-defective, non-integrating viral vector engineered to deliver functional human TGM1 gene into the skin cells.

Bayer reported data from a pre-specified final OS analysis of the Phase III ARAMIS trial ahead of ASCO. Nubeqa decreased the risk of death by 31% compared to placebo in its secondary endpoint of OS in men with non-metastatic castration-resistant prostate cancer (nmCRPC). Updated data also showed the drug delayed the time to pain progression, time to first initiation of treatment with cytotoxic chemotherapy, and time to first symptomatic skeletal event (SSE).

Pfizer reported new Phase Ib clinical trial results from its investigational gene therapy for Duchenne muscular dystrophy (DMD). The Phase Ib trial of PF-06939926, Pfizer’s experimental gene therapy, showed preliminary data in nine ambulatory boys with DMD between the ages of six and 12, with a mean age of eight. The intravenous dosing of the therapy was well-tolerated and showed “encouraging efficacy and manageable safety events.”

The therapy demonstrated durable and statistically significant improvements in a number of efficacy endpoints measured 12 months after infusion. These included sustained levels of mini-dystrophin expression and improvements on the North Star Ambulatory Assessment (NSAA) rating scale. There were three serious adverse event, two that appeared to be immune reactions related to complement activation. They were severe, but all three events fully resolved within two weeks.

Orchard Therapeutics presented new interim data from an ongoing proof-of-concept trial of OTL-203, an ex vivo autologous hematopoietic stem cell (HSC) gene therapy for mucopolysaccharidosis type 1 (MPS-1). As of April 2020, all eight patients with the severe Hurler subtype of MPS-1 have been treated and followed for a minimum of three months, with the longest follow-up 18 months. The treatment showed rapid hematologic reconstitution with neutrophil and platelet engraftment within 21 days of treatment in all patients, and biological efficacy with supranormal IDUA enzyme expression in peripheral blood.

Caladrius Biosciences, with researchers from Cedars-Sinai, Mayo Clinic and The Christ Hospital in Cincinnati, presented full data from the ESCaPE-CMD trial of the company’s autologous CD34+ cell therapy, BLBS16. The data demonstrated highly statistically significant improvement in coronary flow reserve (CFR) correlating with symptom relief for patients with coronary microvascular dysfunction (CMD).

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