Applied Genetic Reports Positive Preclinical Data for Eye Disorder Treatment
Applied Genetic Technologies Corporation (NASDAQ:AGTC) announced the results for its clinical trial related to X-Linked retinitis pigmentosa. The data provided the basis for determining the starting dose and the vector for its current Phase 1/2 clinical trial. The results demonstrated that the company's proprietary AAV vector and engineered RPGR constructs were well tolerated. It also had a positive impact on markers of disease in a canine model of XLRP.
Full length RPGR protein's DNA sequence may contain repetitive sequences which may cause instability during vector engineering and manufacturing. There are two main approaches in this regard. The first one involves removing the repetitive sequence, leading to a shortened RPGR protein while another approach is to cut down instability while producing the full length RPGR protein. Mark S. Shearman, Ph.D., Chief Scientific Officer, AGTC, said, "The results of this study identified an AAV-RPGR vector construct that has optimized safety and efficacy in a highly relevant animal model of human XLRP disease and that large-scale manufacturing that will be essential for making XLRP gene therapy available to the patients who may benefit from it." The company had earlier reported positive interim six-month data from Phase 1/2 XLRP clinical trial.
This dose ranging study used the company's proprietary rAAV2tYF capsid to deliver either a truncated RPGR DNA sequence (hRPGRstb) or an RPGR sequence encoding full-length RPGR protein optimized for stability (hRPGRco) in a canine model of XLRP. After subretinal injection, both transgenes showed similar levels of efficacy. The variables used for this purpose included fundus reflectivity, outer nuclear layer thickness, correction of opsin mislocalization and length of cone inner segments. However, in some cases, hRPGRco showed superior performance. Both the vectors were well tolerated. High dosage group experienced some cases of inflammation and retinal detachment.
Gilead Sciences, Inc. (NASDAQ:GILD) announced positive top-line data from its Phase 2b/3 trial designed to assess the efficacy and safety of filgotinib in biologic-nave or biologic-experienced adult patients with moderately to severely active ulcerative colitis. The drug candidate met all its primary endpoints at 200mg dosage. However, at 100mg dosage, it did not show any statistically significant clinical remission at Week 10.
The results were obtained from SELECTION, a Phase 2b/3, double-blind, randomized and placebo-controlled trial. It involved 1,348 patients being administered oral, once-daily, selective JAK1 inhibitor drug candidate. At week 10, the drug showed clinical remission, which is defined as an endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and 1 point decrease in stool frequency from baseline to achieve a subscore of 0 or 1. In the biologic-nave cohort, 52 percent of patients had nine or higher on a baseline Mayo Clinic Score (MCS) while the corresponding ratio for biologically-experienced cohort stood at 74 percent.
For biologic nave patients cohort, 26.1 percent of the patients showed clinical remission at Week 10 when treated with filgotinib 200 mg in comparison to 15.3 percent hitting the mark in placebo group. The corresponding data for biologic-experienced patients was at 11.5 percent and 4.2 percent, respectively. Both the cohorts showed statistically significant better performance. Patients who showed either a clinical response or remission after 10 weeks of treatment with filgotinib 100 mg or 200 mg were re-randomized to their induction dose of filgotinib or placebo in a 2:1 ratio and treated through Week 58. For the maintenance trial, both the doses met their primary endpoints.
For biologic nave patients, in the induction trial, 1.2 percent patients showed serious adverse events for 200mg dosage, while 4.7 percent suffered these hazards at 100mg dosage. The corresponding data for placebo group stood at 2.9 percent. Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences said, "Patients with moderate to severe ulcerative colitis can struggle to effectively manage their disease. These top-line data suggest that filgotinib could play a role in helping more patients achieve a meaningful and sustained improvement in treatment response with an oral therapy." Ulcerative colitis is a chronic and idiopathic inflammatory disease.
The SELECTION Phase 2b/3 trial is a multi-center, randomized, double-blind, placebo-controlled trial. It comprised two induction trails and a Maintenance Trial. The company is collaborating with Galapagos NV (NASDAQ:GLPG) for developing and commercializing filgotinib in various inflammatory indications. Some of the other clinical trials involving the drug candidate are the DIVERSITY Phase 3 trial in Crohn's disease, the FINCH Phase 3 program in rheumatoid arthritis and the Phase 3 PENGUIN trials in psoriatic arthritis. It is also being tested in Phase 2 studies in uveitis and in small bowel and fistulizing Crohn's disease.
Filgotinib is a lead drug candidate for Gilead and is an investigational agent. The drug candidate is currently under review by the FDA as treatment for rheumatoid arthritis. It is also being reviewed in other geographies including European Union. The drug is expected to face competition from the likes of Rinvoq from AbbVie (NYSE:ABBV) but is still likely to generate impressive revenue stream. Since the drug failed to meet its primary endpoint at 100mg dosage, the prospects for 200mg dosage seem better.
Apellis Pharmaceuticals Inc. (NASDAQ:APLS) announced that it is in the process of submitting a New Drug Application (NDA) for pegcetacoplan during the second half of 2020. The application will be accompanied by the data from the Phase 3 PEGASUS trial comparing pegcetacoplan to eculizumab in patients suffering from Paroxysmal Nocturnal Hemoglobinuria. The company is also in the process of carrying out discussions with authorities in the European Union.
The PEGASUS study is a randomized, multi-center, active comparator and open label controlled Phase 3 study. The trial involved 80 adult patients suffering from Paroxysmal Nocturnal Hemoglobinuria. The primary endpoint of the trial was to assess the efficacy and safety of pegcetacoplan compared to eculizumab. Participants were required to be on eculizumab (stable for at least three months) with a hemoglobin level of <10.5 g/dL at the screening visit. All participants completing the randomized controlled period proceeded to the open-label pegcetacoplan treatment period. They were administered pegcetacoplan in the randomized and controlled period.
The study met its primary endpoint as the data showed superior performance by pegcetacoplan to eculizumab. The drug candidate led to a statistically significant improvement in hemoglobin levels at 16 weeks. During the run-in period of four weeks, the participants were given 1080 mg of pegcetacoplan twice a week along with their current dose of eculizumab. For 16-week randomized, controlled period, the participants were randomized and they were either given their current dose of eculizumab or 1,080 mg of pegcetacoplan twice weekly. The data also showed that pegcetacoplan had the drug safety profile comparable to eculizumab.
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Applied Genetic Reports Positive Data, And Other News: The Good, Bad And Ugly Of Biopharma - Seeking Alpha
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