Prosensa announces Lancet Neurology pub­li­ca­tion of an explorato­ry phase II study (DEMAND II) demon­strat­ing effi­ca­cy and safe­ty of dris­apersen in patients with Duchenne mus­cu­lar dys­tro­phy

Leiden, The Netherlands, Sept. 8, 2014 (GLOBE NEWSWIRE) — LEIDEN, The Netherlands – September 8, 2014 – Prosensa Holding N.V. (NASDAQ: RNA), the bio­phar­ma­ceu­ti­cal com­pa­ny focus­ing on RNA-mod­u­lat­ing ther­a­peu­tics for rare dis­eases with high unmet need, today announced that the full data from its explorato­ry, dou­ble-blind, place­bo-con­trolled Phase II study (DEMAND II/ DMD114117/ NCT01153932) of dris­apersen in patients with Duchenne mus­cu­lar dys­tro­phy (DMD) have been pub­lished in Lancet Neurology
The pub­li­ca­tion of the results of the study, which inves­ti­gat­ed the effi­ca­cy and safe­ty of dris­apersen giv­en for 48 weeks, con­firms the pos­i­tive out­come of the DEMAND II study, which met its pri­ma­ry end­point, with no report­ed major safe­ty con­cerns.
Top line study results were first pre­sent­ed in April 2013. Drisapersen received Breakthrough Therapy des­ig­na­tion in June 2013 from the FDA based upon this dataset. The DEMAND II study eval­u­at­ed the effect of two dif­fer­ent dos­ing reg­i­mens of dris­apersen (con­tin­u­ous and inter­mit­tent) in 53 patients with DMD, at 13 spe­cial­ist clin­ics in nine coun­tries. At week 25 (pri­ma­ry end­point), the mean 6-minute walk test dis­tance (6MWD) had increased by 31•5m (SE 9•8) from base­line for con­tin­u­ous dris­apersen, giv­ing a mean dif­fer­ence in change from base­line of 35•1m (95% CI 7•59 to 62•60; p=0•014) ver­sus place­bo. This is the first time that a dis­ease mod­i­fy­ing ther­a­py in DMD has shown a sta­tis­ti­cal­ly sig­nif­i­cant and clin­i­cal­ly mean­ing­ful treat­ment dif­fer­ence from place­bo as mea­sured by the 6MWD.
At week 49, the mean dif­fer­ence in 6MWD (35.9m) was clin­i­cal­ly mean­ing­ful though no longer sta­tis­ti­cal­ly sig­nif­i­cant (p=0.051). No sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in 6MWD changes from base­line was observed between inter­mit­tent dris­apersen and place­bo at week 25 or 49, although analy­sis of the com­bined inter­mit­tent and con­tin­u­ous dris­apersen treat­ment groups com­pared with com­bined place­bo groups showed a sig­nif­i­cant dif­fer­ence in 6MWD at week 49 of 31m (95% CI 0•47 to 62•5, p=0•047). Most patients report­ed mild-to-mod­er­ate on-treat­ment adverse events; no adverse events led to with­draw­al from the study.
Immunofluorescence showed increas­es in dys­trophin pro­tein expres­sion in biop­sies at week 25 com­pared with pre-treat­ment mea­sures in both dris­apersen groups, although no cor­re­la­tion with 6MWD was seen. A decrease in serum cre­a­tine kinase con­cen­tra­tions was seen for both dris­apersen groups com­pared with place­bo­sug­gest­ing an improve­ment in the integri­ty of mus­cle fibers.
Lead author and prin­ci­ple inves­ti­ga­tor in the study, Professor Thomas Voit MD from the Institut de Myologie, Universite Pierre et Marie Curie, Paris, France said: “Publication of this key paper on dris­apersen in one of the most esteemed peer-reviewed sci­en­tif­ic jour­nals in our field is a great endorse­ment of the robust­ness of the DEMAND II study and the clin­i­cal sig­nif­i­cance of the results. The DEMAND II study sup­ports the effi­ca­cy of dris­apersen in the con­text of the over­all clin­i­cal pro­gram, and I am proud to be part of this impor­tant effort to deliv­er a much need­ed treat­ment option to DMD patients.”
Dr. Giles Campion, Prosensa’s Chief Medical Officer and co-author added “The DEMAND II study results are a pos­i­tive indi­ca­tion that dris­apersen can offer real hope as a DMD treat­ment as it showed a sig­nif­i­cant improve­ment in the pri­ma­ry end­point in this group of DMD patients. These data will form an essen­tial part of our reg­u­la­to­ry sub­mis­sions, which are cur­rent­ly in prepa­ra­tion.”
In June, Prosensa announced that the United States Food and Drug Administration (FDA) out­lined a reg­u­la­to­ry path for­ward for dris­apersen, under an accel­er­at­ed approval path­way, based upon exist­ing data, includ­ing the DEMAND II study. Prosensa remains on track to pur­su­ing reg­u­la­to­ry fil­ings for dris­apersen, ini­tial­ly in the United States and Europe, with the FDA sub­mis­sion planned before the end of the year and an EMA sub­mis­sion short­ly there­after.

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