Duchenne Muscular Dystrophy (DMD)

DMD is a serious genetic neuromuscular disease that affects males of all ethnicities. DMD affects motor skills, results in progressive muscle loss and skeletal deformities, including spinal deformation, and eventually leads to respiratory failure and cardiac complications that result in premature death. The average age of onset is between three and five years of age. Dilated cardiomyopathy and respiratory failure are commonly associated with this chronic disease leading to early morbidity and mortality in DMD patients, frequently in late teens ¾ early twenties.

With disease progression, DMD patients suffer from severe medical conditions, and are often confined to a wheelchair during their teenage years. Cardiac complications are present in virtually all DMD patients, with cardiac function progressively deteriorating with age, especially during adolescence. Respiratory failure is also a serious effect of DMD, but with the introduction of ventilatory support, cardiac failure has become the major cause of premature death. There is currently no effective treatment for DMD.

Santhera has been granted orphan drug designation in the US and Europe for Catena® in DMD.

Clinical development of Catena® in DMD

On October 29, 2007, Santhera announced positive, first results from a 12 month Phase IIa clinical trial with Catena® in DMD. The Company is committed to further clinical development of the compound.

This exploratory Phase IIa trial was a double-blind, randomized, placebo-controlled study conducted at the University of Leuven, Belgium. In total 21 DMD patients between the age of 8 and 16 years were enrolled to assess the efficacy and tolerability of one dose level of Catena® (450 mg/day) compared to placebo. 13 patients were receiving Catena® while 8 patients were randomized to the placebo group.

There were no drop-outs in the study and the compliance was very good. Importantly, there was no difference in the safety and tolerability of Catena® compared to placebo underlining again the excellent safety profile of Catena® also in this pediatric population.

The primary objective was to assess whether Catena® improves or slows the decline in cardiac function in DMD patients, applying a comprehensive echocardiographic approach that included cardiac tissue Doppler and strain rate imaging technology.

The primary endpoint was an assessment of the change in contractility of the region of the heart muscle that is affected early and most severely in DMD patients, measured by the peak systolic radial strain of the left ventricular inferolateral wall. After treatment for twelve months with Catena®, DMD patients showed a trend to improve on this functional cardiac parameter compared to placebo.

In addition to these data, patients on Catena® improved also on certain respiratory parameters. Most striking and statistically significant was the improvement of DMD patientså lung function measured by peak flow. Patients treated with Catena® ameliorated on this parameter, while patients on placebo deteriorated over the study period.

Santhera intends to seek protocol advice from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in preparation of the further clinical development of Catena®.