Clinical Trials

* On September 26, 2014, Prosensa announced that it has extended its comprehensive program of re-dosing of drisapersen in patients with Duchenne muscular dystrophy (DMD) into Europe, with the PRO051-02/DMD114673 sites re-opening, beginning with Belgium. This follows quickly on the re-dosing program that began in the US last week. The two sites in the PRO051-02/DMD114673 extension study, the longest running study with a disease modifying therapy in DMD, had been treating boys with drisapersen for almost 4 years prior to dosing being suspended in September 2013. Efficacy data from 10 boys analyzed in this study at 177 weeks showed a mean change from their baseline six-minute walk test (6MWT) of only -25 meters, including two boys with more severe disease who lost ambulation early on in the study. The re-dosing program in Belgium is being led by Dr. Nathalie Goemans, Head of the Neuromuscular Reference Center for Children at the University Hospitals Leuven (UHL) and in Sweden is led by Dr. Mar Tulinius, Professor and Chief Physician at the University of Gothenburg, both key investigators in various drisapersen studies. Prosensa is urgently progressing preparations to roll out similar programs of re-dosing in other European countries and globally for all previously treated drisapersen patients, via expanded access, compassionate use or named patient programs, where feasible. "Prosensa remains on track to pursuing regulatory filings for drisapersen, initially in the US and Europe, with an FDA submission planned before the end of the year and an EMA submission shortly thereafter" re-confirmed Hans Schikan, Prosensa's CEO.
* On September 17, 2014, Prosensa announced that a comprehensive program of re-dosing has commenced, with the first patients now re-dosed in the United States. All dosing in the drisapersen clinical program had been placed on hold by GSK on September 20, 2013, upon announcement of the DEMAND III study results. The re-dosing program in North America will include up to 72 patients across 14 sites who had participated in the drisapersen DEMAND V (Phase II) & DEMAND III (Phase III) studies. Prosensa regained the rights to drisapersen from its previous partner GSK in January 2014, and soon thereafter committed to re-dose patients as quickly as possible, accepting that the transfer of data and clinical materials, and the re-engagement with clinical sites would be a complex process. Drisapersen is administered subcutaneously, with once weekly dosing. Prosensa is aware of the burden that clinical trials can place on the families, and in this protocol efforts have been made to alleviate burden and facilitate participation. Prosensa aims to enable home-dosing where feasible, and cost-free transport with straightforward logistics for clinical centers, through collaboration with Greenphire and the Medical Research Network (MRN).

Greenphire is the industry's leading provider of clinical payment technology and has made its proprietary ClinCard System available for patients in the US and Canada. The ClinCard system with Travel Module will help Prosensa manage the complex travel arrangements required for the patients involved in this study, which will maintain a truly patient-centric environment. Patients, along with their caregivers and family members, can make use of Greenphire's expert travel services to arrange travel for expected study visits with minimal out-of-pocket costs. Similarly, Greenphire's logistical support allows clinician investigators to focus their time and attention where it's needed: patient care and study execution. Prosensa is also in in preparations for similar programs of re-dosing and support for all previously treated drisapersen patients. In June, Prosensa announced that the FDA outlined a regulatory path forward for drisapersen, under an accelerated approval pathway, based upon existing data, including the DEMAND II study, which was recently published in the Lancet Neurology. Prosensa remains on track to pursuing regulatory filings for drisapersen, initially in the US and Europe, with an FDA submission planned before the end of the year and an EMA submission shortly thereafter.

* On May 1, 2014, Prosensa provided the data analysis of its second open-label extension study (DEMAND IV/DMD114349) of drisapersen in boys with Duchenne Muscular Dystrophy (DMD) during the 66th American Academy of Neurology (AAN) Annual Meeting in Philadelphia, PA. The Company also provided an update on the drisapersen clinical program earlier this week in a letter sent to patient group representatives and clinical investigators and will present a corporate update during an investor briefing on May 1. Following positive feedback from patients and investigators regarding the willingness and desire of patients to go back on drisapersen and encouraging analyses of its clinical trial data, Prosensa has confirmed that it will re-dose an initial cohort of boys in the third quarter of 2014. The Company has made significant progress in the transition of the program from its former partner, GSK, and expects to communicate on a regulatory path forward for drisapersen before the end of June. In a poster and presentation on Wednesday, April 30 at the AAN, Dr. Nathalie Goemans, Head of the Neuromuscular Reference Center for Children at the University Hospitals Leuven (UHL) in Belgium and one of the key investigators in various drisapersen studies confirmed the earlier preliminary analysis of the results of DEMAND IV/DMD114349, which include data from 96 weeks of continuous drisapersen treatment. The poster included detailed data up to Week 48 (total of 96 weeks of treatment) from the second open-label extension study of drisapersen in 113 boys with DMD (DEMAND IV), who had previously completed a 48-week, double-blind, placebo-controlled treatment phase in one of two feeder studies (DEMAND II/DMD114117 and DEMAND III/DMD114044). In the six minute walk test (6MWT), boys from the DEMAND II study declined by only 5 meters over 96 weeks on continuous drisapersen (6mg/kg/week) compared with 57 meters in boys who had placebo/delayed treatment. Furthermore, boys of 7 years or younger in DEMAND IV improved from their baseline 6MWT by 8 meters with continuous drisapersen treatment compared with a 29 meter decline for patients in the placebo/delayed treatment arm. The extension study was designed to monitor the long-term safety and efficacy of drisapersen over the course of two years at more than 50 sites in 24 countries. In a letter to all participating investigators and patient groups sent earlier this week, Prosensa confirmed it is on track with its re-dosing plans, which will take a staged approach. Dr. Nathalie Goemans (UHL, Belgium) and Dr. Craig McDonald (UC Davis, Sacramento, USA), who will be participating at an investor briefing on May 1, will be amongst investigators working with Prosensa to undertake re-dosing protocols with drisapersen. The first wave of re-dosing in the third quarter will focus on sites in North America and Europe. Patients in North America will be re-dosed under existing extension protocols and patients in Europe will either participate in a new treatment protocol or via an appropriate expanded access program. 

* On January 16, 2014, Prosensa, the Dutch biopharmaceutical company focusing on RNA-modulating therapeutics for rare diseases with high unmet medical need, has announced initial findings from further analyses from the aggregate data from the clinical development program of drisapersen for the treatment of Duchenne Muscular Dystrophy (DMD). With data from more than 300 patients Prosensa has the largest clinical data set in DMD. In order to advance the general understanding of DMD, Prosensa has also announced that it will make certain data from the drisapersen clinical program available to the scientific community. In addition it has initiated a study to better understand the natural history of DMD and is also exploring potential biomarkers that could be of use as indicators of efficacy in DMD clinical trials.

The subset analyses focus on outcomes in DMD boys seven years or younger and those over seven years old as measured by the six-minute walk test (6MWT). In all studies, a treatment difference was seen in the younger patient population. Notably, the preliminary analysis of the 96 week extension data from those participating in the phase III DMD114044 (DEMAND III) study shows a 49 meter difference between those on continual treatment (n=52) and those who had been on placebo for 48 weeks followed by active drug (n=31).  Those previously participating in the DMD114117 study (DEMAND II) showed a 52 meter difference at 96 weeks (n=13, n=17, respectively).

Drisapersen, (previously GSK2402968/PRO051), an antisense oligonucleotide which induces exon skipping of exon 51, is currently in-late stage development for DMD. Drisapersen has orphan drug status in the EU, US, Australia and Japan. In June 2013, drisapersen was granted Breakthrough Therapy designation by the US Food and Drug Administration.

* On September 20, 2013, GSK and Prosensa have announced that GSK’s Phase III clinical study of drisapersen for the treatment of Duchenne Muscular Dystrophy (DMD) patients with an amenable mutation, did not meet the primary endpoint of a statistically significant improvement in the 6 Minute Walking Distance (6MWD) test compared to placebo. A total of 186 boys were randomised to this double-blind, placebo-controlled study (DMD114044) and received drisapersen at a dose of 6mg/kg/week (N=125) or placebo (N=61) via subcutaneous injection over 48 weeks. The difference in 6MWD (mean (CI) 10.33m (-14.65, 35.31), p=0.415) between drisapersen and placebo groups did not reach statistical significance. There was no treatment difference in key secondary assessments of motor function: 10-meter walk/run test, 4-stair climb and North Star Ambulatory Assessment.

The most commonly reported adverse events included injection site reactions (78% for drisapersen vs 16% for placebo) and renal adverse events (including subclinical proteinuria; 46% for drisapersen vs 25% for placebo). No patients had thrombocytopenia.
Full evaluation of the benefit-to-risk profile of drisapersen treatment across all studies is anticipated to be completed by year end. This may include analyses of pooled results from various drisapersen studies.
“We are committed to evaluating the outcome of this study in the context of the overall development programme with experts in the field, and we expect such evaluation to help inform our next steps for drisapersen. It is our hope that progress will be made in an effort to help boys with DMD.” commented Carlo Russo, Senior Vice President, Head of GSK Rare Diseases Research & Development. “While we are disappointed that this study did not meet its primary endpoint, we remain committed to the overall programme and will continue to work closely with GSK.” said Hans Schikan, Chief Executive Officer of Prosensa.
Results have been submitted for presentation at forthcoming scientific meetings and will also be submitted for publication in a scientific peer-reviewed journal.