ALLSCHWIL, Switzerland, Oct. 26, 2005 (PRIMEZONE) -- Actelion Ltd (SWX:ATLN) (Other OTC:ALIOF) announced today a poster presentation at the annual conference of the American Society of Human Genetics (ASH-G) of one-year results from a randomized controlled study evaluating safety and efficacy of miglustat (Zavesca(r)) in patients suffering from Niemann Pick Type C (NP-C), a rare genetic disease associated with multiple neurological manifestations.
Although not statistically significant, the 29-patient-study showed trends toward improvement or stabilization in terms of saccadic eye movements (by electrophysiological assessment) and swallowing and audition (by clinical assessment) in patients receiving miglustat compared to standard of care. The study will continue as planned for another 12 months, during which time all patients will receive miglustat. A complete discussion of currently available study findings are contained in: Patterson M., Vecchio D., Prady H., Ait-Aissa N., Abel L., Wraith E. -- Poster 2505/T, ASH-G 2005 (Salt Lake City).
Marc Patterson, M.D., FRACP, Professor and Head, Division of Pediatric Neurology at Columbia University New York/USA, commented: "We know already that miglustat crosses the blood-brain barrier and accesses the brain. For the first time, we have been able to observe some potentially beneficial effects in patients with NP-C. I am also encouraged with these observations as they could suggest some restoration of function in neurons that have been altered by the disease process. As such, this study is another step forward in our quest to understand and potentially treat this complex disease."
The safety profile in this study evaluating miglustat 200 mg three times a day was consistent with safety information generated with the use of miglustat 100 mg three times a day.
About Niemann Pick Type C
NP-C is a fatal, degenerative, genetic condition primarily affecting children and teenagers, but which can strike at any age. The symptoms are caused by the storage of some glycosphingolipids within certain cells in the body, including the brain. It is relentlessly progressive and most patients die within five to ten years of diagnosis. Neurological deterioration is a key feature of the disease, and can manifest itself as clumsy body movements, balance problems, slow and slurred speech, difficulty in swallowing, problems with eye movements and seizures. Intellectual decline is common. In the final stages of the disease the child or young adult is frequently bedridden, has little muscle control and is intellectually impaired. There is currently no treatment option for this condition.
Details on study and results
The study is being carried out at both Columbia University, New York (U.S.) and The Royal Manchester Children's Hospital (U.K.). Twenty-nine patients (greater than 12 years old) with NP-C were randomized to receive either miglustat 200 mg three times daily (twenty patients) or standard care (nine patients) for 12 months and a series of clinical, electrophysiological and quality of life assessments were conducted at regular intervals. The dose double that recommended for Gaucher Disease type 1 (GD1), in order to increase brain exposure to miglustat.
Twenty-five patients have completed the first 12-month study period and four have discontinued treatment (three in the miglustat group, one in the standard care group). Results from the 12-month data showed improvement in horizontal saccadic eye movements (by blinded centralized assessment) and improvement in swallowing, none reaching formal statistical significance. The analysis also showed stabilization in auditory acuity in treated patients compared with deterioration in the untreated group.
The safety profile of miglustat observed in this study was consistent with the results obtained in patients with GD1 treated with miglustat 100 mg three times daily, particularly regarding weight loss and gastro-intestinal disturbances.
Based on these results, the study will continue as planned for a further 12 months during which time all patients will receive miglustat and will be followed with the same set of assessments.
About Substrate Reduction Therapy with miglustat
Miglustat is a small molecule with a large tissue distribution and is administered orally. It works on the principle of substrate reduction therapy, by reducing the rate of formation of glucosylceramide, a precursor of glycosphingolipids that are stored in NP-C. It is the storage of these lipids that contributes to neuronal dysfunction and ultimately neuronal death in several areas of the central nervous system. Miglustat is currently indicated in Gaucher Disease type 1, another glycosphingolipid storage disorder, for adult patients who are unable or unwilling to receive enzyme replacement therapy.
Note to the Editor:
Niemann Pick Type C
Niemann Pick is a rare genetic disorder and it occurs in three forms, type A, B and C each affecting the body's metabolic processes and caused by specific genetic mutations. Niemann Pick Type C (NP-C) is different from the other forms of the disease at a biochemical level and is always fatal. It is caused by a mutation in one of two different genes NPC-1 (most commonly) or NPC-2 and over 180 different gene mutations have been identified. It is thought that these two genes are involved in the trafficking of lipids within the cells which is a key process in cellular maintenance. However the intricacies of this complicated disease pathology are still under research. The symptoms of NP-C have been traditionally explained by the storage of cholesterol within cells, but there is also growing evidence that a variety of other lipids (glycosphingolipids) accumulate within cells in the brain causing the debilitating neurodegenerative manifestations of the disease. NP-C is difficult to diagnose due to the variety and time distribution of symptoms.
About Zavesca(r) in Type 1 Gaucher Disease (GD1)
Zavesca(r) (miglustat) is the first oral treatment option for adults with Type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option. It is the first in a new class of drugs known as substrate reduction therapy (SRT). Zavesca(r) reduces the rate of formation of glucosylceramide, a glycosphingolipid (GSL) that accumulates in GD, to a level that can be cleared by the remaining enzyme. This prevents the build up of excess glucosylceramide in the macrophage cells. Zavesca(r) is approved and available in the European Union, United States, Canada, Israel and Switzerland.
Zavesca(r) safety information
Peripheral neuropathy has been reported in Type 1 Gaucher patients treated with Zavesca(r). Patients should undergo a neurological exam at the start of treatment and regularly thereafter. Zavesca(r) should be reassessed in patients who develop symptoms of peripheral neuropathy. Zavesca(r) may cause foetal harm if administered to a pregnant woman and is contraindicated in women who are or who may become pregnant; patients should be apprised of the potential hazard to the foetus. There is a risk of impaired fertility in men. Men should maintain reliable contraceptive methods and not plan to conceive while taking Zavesca(r) and for 3 months thereafter.
Actelion Ltd
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion's first drug, Tracleer(r), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer(r) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -- the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).