Gilead and Galapagos announced that FINCH 2, a global, randomized, placebo-controlled, Phase 3 study of filgotinib, an investigational, selective JAK1 inhibitor, in adults with moderately-to-severely active rheumatoid arthritis and prior inadequate response/intolerance to biologic agents, achieved its primary endpoint in the proportion of patients achieving an American College of Rheumatology 20 percent response (ACR20) at Week 12. Also at Weeks 12 and 24, the proportion of patients achieving ACR50 and ACR70, low disease activity (LDA, DAS28(CRP) ≤ 3.2), and clinical remission (DAS28(CRP) < 2.6) were significantly higher for patients receiving once-daily filgotinib 100 mg or 200 mg compared to patients receiving placebo.

Filgotinib was generally well-tolerated in the FINCH 2 trial, with no new safety signals compared to those reported in previous trials of filgotinib. Treatment-emergent adverse events and serious adverse events were mostly mild or moderate in severity. Serious adverse events occurred in 3.4, 5.2 and 4.1 percent of the patients in the placebo, 100mg and 200mg groups, respectively. The proportion of patients who discontinued study drug due to treatment-emergent adverse events was also similar across groups. Two cases of uncomplicated herpes zoster were reported in each filgotinib group. Two major adverse cardiovascular events (MACE) were identified, one subarachnoid hemorrhage in the placebo group and one myocardial ischemia in the filgotinib 100 mg group. There was one case of non-serious retinal vein occlusion in the filgotinib 200 mg group and no reports of deep venous thrombosis (DVT) or pulmonary embolism (PE). There were no deaths, malignancies, gastrointestinal perforations, or opportunistic infections, including active tuberculosis.

Detailed findings from the FINCH 2 study will be submitted for presentation at a future scientific conference.

“Gilead is committed to the development of new therapies that offer meaningful benefit for people living with rheumatoid arthritis and other serious inflammatory diseases,” said John McHutchison, MD, Chief Scientific Officer, Head of Research and Development, Gilead Sciences. “These initial Phase 3 data support the potential of filgotinib, in combination with select disease modifying drugs, to help patients with active rheumatoid arthritis who do not adequately respond to current biologic disease modifying agents. These data are particularly encouraging as we look ahead to Phase 3 results from the ongoing FINCH 1 and 3 trials, which are exploring filgotinib in other populations of patients with rheumatoid arthritis.”

“We are pleased that filgotinib has demonstrated significantly improved clinical responses in this difficult to treat population,” said Dr. Walid Abi-Saab, Chief Medical Officer at Galapagos. “The good tolerability in this study is also very encouraging.”

Filgotinib is investigational and not approved anywhere globally. Its efficacy and safety have not been established. For information about the clinical trials with filgotinib: www.clinicaltrials.gov

Source: Gilead

ProQR Therapeutics, a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, announced results from a planned interim analysis of its Phase 1/2 trial of QR-110 in patients with Leber’s congenital amaurosis 10 (LCA10) due to the p.Cys998X mutation in the CEP290 gene. LCA10 typically leads to childhood blindness and has no available treatment options. In the trial, QR-110 demonstrated rapid and sustained improvement in vision in patients with LCA10, as measured by visual acuity and the mobility course performance, as well as being well-tolerated with no serious adverse events recorded. Results from this interim analysis were presented earlier today at the Retinal Degeneration 2018 meeting in Killarney, Ireland, by principal investigator Artur Cideciyan, Ph.D., research professor of ophthalmology at the Scheie Eye Institute, University of Pennsylvania.

“The results of this interim analysis are encouraging and met our decision criteria to stop enrollment in this study and progress to a pivotal Phase 2/3 trial,” said David Rodman, M.D., executive vice president of research and development of ProQR. “We observed a clinically meaningful improvement in vision in the treated eye as measured by both mechanistic and potential registration endpoints. Consistent with predictions based on our patient derived optic-cup models, improvement in visual function was observed as early as two months after treatment and was maximal and stable by three months and thereafter. We are very grateful to the study participants, their caregivers, and the investigators and their staff for the support in the development of QR-110 in this trial.”

Thaddeus P. Dryja, M.D., professor of ophthalmology at Harvard Medical School and Massachusetts Eye and Ear and member of the National Academy of Sciences, commented, “These results are the first human data to evaluate the clinical utility of RNA-based therapeutics in a human photoreceptor disease, particularly one with a severe unmet medical need. While a confirmatory trial will be required to establish the full potential of QR-110 in LCA10, these results suggest that therapeutic oligonucleotides have the potential to be broadly applicable to a wide spectrum of inherited retinal disorders.”

Based on the emerging findings from the Phase 1/2 trial, the Company agreed with the FDA to submit a protocol to progress to a pivotal Phase 2/3 trial. In light thereof, the originally planned interim analysis at six months treatment was accelerated to the point when eight patients had reached three months of treatment. Given comparable activity was observed in the first two dose levels, the trial did not escalate up to the high dose and trial enrollment has stopped, in anticipation of the start of a Phase 2/3 trial.

Results from the interim analysis

Efficacy data: Approximately 60% of subjects showed a clinically meaningful response in visual acuity and mobility course endpoints at three months of treatment and there was general concordance across the endpoints. Efficacy signals were observed within two months with maximal benefits seen within two to three months post treatment initiation. A secondary analysis assessing all available data demonstrated that observed effects on efficacy were durable beyond three months.

Visual acuity: In the majority of patients, there was a substantive overall improvement in best corrected visual acuity (BCVA) as assessed by the Berkeley Rudimentary Vision Test (BRVT) and the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. At three months of treatment, the mean improvement (and standard error of mean, SEM) was -0.67 LogMAR (SEM 0.32) with 62.5% of subjects showing an improvement of greater than -0.3 LogMAR from baseline, which is considered clinically meaningful. The mean change in the contralateral eye was 0.02 LogMAR (SEM 0.05).

Mobility course: Effects on visual acuity correlated with effects on mobility. In the majority of patients there was a substantive overall improvement in functional visual performance as assessed using a series of mobility courses at increasing difficulty and multiple light intensities. At three months of treatment, the mean improvement in navigating the mobility course was 2.6 levels (SEM 1.2) with 57.1% of subjects improving by more than 2.0 levels, which is regarded as clinically meaningful. The mean change in the contralateral eye was 1.36 (SEM 1.04).

Full field stimulus test (FST): Improvements in visual function were supported by a meaningful increase in the ability to detect flashes of red or blue light as determined by the FST. After three months of treatment mean improvement in red light sensitivity was -0.74 log Cd/m² (SEM 0.35) and improvement in blue light sensitivity was -0.91 log Cd/m² (SEM 0.38).

Ocular Instability (OCI): Additionally, the majority of patients improved on nystagmus (involuntary eye movements in low vision patients), with a mean change of log -0.14 mm (SEM 0.08) in OCI.

Safety: Out of the 10 subjects dosed in the study, one subject has received all four doses and three have received three doses, representing a combined total of more than 1,500 treatment days. So far QR-110 was well tolerated with no serious adverse events related to treatment or procedure. All data and safety monitoring committee (DSMC) reviews were completed with no restrictions on further dose escalation or pediatric dosing.

Start of Phase 2/3 pivotal “ILLUMINATE” trial

The Company has agreed with the FDA to submit a protocol to start a Phase 2/3 trial that could serve as the sole registration trial, to be called “ILLUMINATE”. The preliminary design for “ILLUMINATE” is a double-blind, controlled, 12-month study. The trial is expected to initially enroll 30-40 patients with LCA10 due to one or two copies of the p.Cys998X mutation and could be adaptively repowered. The primary endpoints in this trial are expected to include the mobility course and visual acuity, among others. The trial is expected to be conducted at centers in North America and select European countries. Pending completing discussions on the design of the study with the FDA in 2018, the trial is expected to start in the first half of 2019. In parallel to the pivotal Phase 2/3 trial, the Company plans to start a trial in patients <6 years old.

Source: ProQR

While research groups in China have already started testing CRISPR in humans, CRISPR Therapeutics and Vertex Pharmaceuticals are the first companies to sponsor a human trial of the gene editing technology. The trial will take place at a single site in Germany and will test a gene therapy in patients with beta thalassemia.

Both disorders are caused by mutations in the beta-globin gene, which codes for a part of hemoglobin, the oxygen-carrying component of red blood cells. This results in missing or defective hemoglobin. CTX001 was developed on the knowledge that fetal hemoglobin—found in newborn babies but later replaced by adult hemoglobin—can be protective in adults who have blood disorders.

CTX001 uses CRISPR gene-editing ex vivo—that is, outside the body. A patient’s cells are harvested and edited to increase fetal hemoglobin levels in the patient’s blood cells. The edited cells are then infused back into the patient where they are expected to produce blood cells with fetal hemoglobin and compensate for defective adult hemoglobin.

The new trial will test CTX001 in up to 12 adult patients who have transfusion-dependent beta thalassemia, according to an announcement on Clinicaltrials.gov. It will take place at a single hospital in Regensburg, Germany.

“CRISPR Therapeutics and Vertex are advancing CTX001 as the first gene editing treatment for both sickle cell disease and beta thalassemia using the CRISPR/Cas9 technology, and have now opened the beta thalassemia study for enrollment in a Phase 1/2 trial in Europe,” said a CRISPR Therapeutics spokesperson via email. “This is one important step of many toward bringing the promise of this new technology to patients with serious diseases like SCD and beta thalassemia, and we are thrilled to be at the forefront of what we believe may be a fundamental change in the treatment of disease.”

For a time, it looked like Editas Medicine would be the first to launch a human trial, with plans to start testing a CRISPR treatment for a rare form of blindness in 2017. Manufacturing issues delayed the timeline to 2018, with CEO Katrine Bosley saying in the company’s second-quarter update that the IND filing is slated for October.

Source: FierceBiotech

Premier Mark Rutte roept “alle ouders nog eens nadrukkelijk op” hun kinderen te laten inenten. De minister-president mengt zich in de discussie over vaccinatie nu steeds meer kinderen niet worden ingeënt.

Rutte “snapt” dat ouders zich zorgen maken om het groeiende aantal niet-ingeënte kinderen. De bescherming die de prik biedt is “niet alleen voor je eigen kinderen, maar dat doe je ook omdat je omgeving kwetsbaar is als dat onvoldoende gebeurt”.

Het kabinet gaat onderzoeken of het mogelijk is kinderdagverblijven de mogelijkheid te bieden niet-ingeënte kinderen te weigeren. Rutte waarschuwt dat “daar wel veel haken en ogen aan zitten”. Maar omdat het kabinet volgens hem de zorgen van ouders deelt, wil het toch onderzoeken of dat verstandig en haalbaar is.

Een nationale vaccinatieplicht gaat Rutte nog te ver.

Bron: Skipr