Zavesca^=AE (Miglustat) First Treatment Available in = Canada for Rare=20 Progressive Niemann-Pick Type C Disease

LAVAL, CANADA--(Marketwire - March 23, 2010) - = Actelion Ltd=20 (SIX:ATLN) announced the approval of a new indication for=20 Zavesca^=AE (miglustat) in Canada; the first and only = treatment=20 available for people with Niemann-Pick type C (NP-C) disease = [1]. NP-C is a=20 rare, genetic disease with significant neurological deterioration that = can be=20 fatal and affects infants, children and adults [2,3].

Currently there is no cure for NP-C. Prior to Zavesca^=AE = patient=20 management was restricted to symptom relief = [4]. Zavesca^=AE is=20 indicated to slow the progression of some of the neurological = manifestations in=20 patients with Niemann-Pick Type C disease [1]. Neurological = deterioration=20 is the key feature of NP-C, which manifests in a variety of symptoms = including:=20 eye movement problems (vertical supranuclear gaze palsy); balance = disorders=20 (ataxia); difficulty swallowing (dysphagia); slurred and irregular = speech=20 (dysarthria); a lack of muscle control (dystonia) and=20 seizures. Intellectual decline which often leads to dementia, is = also=20 common and in the final stages of the disease the patient is often = bedridden=20 [2,5].

In a clinical trial (OGT 918-007) where patients were given either = 200 mg of=20 Zavesca^=AE three times a day (in pediatric patients the dose = was=20 adjusted to body surface area) or standard of care for 12 months; a mean = improvement was observed in the primary endpoint of horizontal saccadic = eye=20 movement (HSEM) velocity (the ability to move eyes rapidly from = side-to-side) in=20 the Zavesca^=AE treated group versus deterioration in the = standard care=20 group, and swallowing and ambulatory functions were better = maintained.[4].

In an extension study, where all patients were treated with=20 Zavesca^=AE for a further 12 months, overall, the majority of=20 adult/juvenile and pediatric patients with NP-C remained at least stable = in=20 important markers of neurological disease progression. Mobility = remained=20 stable in 67% of patients; swallowing capacity was improved or stable in = 79% of=20 patients with water, 86% of patients with puree and in 93% of patients = with both=20 soft lumps and cookies [6].

Serge Melan=E7on, M.D., Montreal Children Hospital, commented: = "Health Canada's=20 approval of Zavesca^=AE (Miglustat) for the treatment of = Niemann-Pick=20 Type C disease is a wise choice and is very good news for patients and = their=20 families. Until now, no drug was effective against the neurologic = manifestations=20 associated with this debilitating familial disease. Canadian physicians = will be=20 without a doubt happy to have this therapy, which is already recognized = in=20 Europe and elsewhere around the world, to relieve their patients' = symptoms. As a=20 clinical geneticist who has been dedicated to treating rare hereditary = diseases=20 for several years now, it is my fervent hope that the provinces will = follow=20 Health Canada's lead and facilitate access to Zavesca^=AE for = patients=20 who have already been diagnosed with this disease."

Sandra Sirrs, M.D., Vancouver Hospital and Health Sciences Centre, = commented:=20 "I am pleased to have a promising treatment to offer patients with this=20 previously untreatable devastating disease."

Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion = commented: "I=20 am very proud that Actelion =96 together with the scientific community = =96 has been=20 able to demonstrate the role of Zavesca^=AE in reducing the = progression=20 of clinically relevant neurological symptoms in patients with NP-C. I = would like=20 to thank both the patients and their families who, over the years, have = been=20 involved in our clinical program with so much dedication, as well as all = the=20 clinical experts for their continuous support. Actelion will continue to = support=20 the rare disease community in its efforts to advance science and = medicine for=20 the patient."

Zavesca^=AE has been shown to be generally well tolerated = in patients=20 with NP-C, with the most common adverse events being =96 among others = =96 diarrhea,=20 weight loss and tremor [1, 4].

Zavesca^=AE, which was already approved in Canada for the = treatment=20 of adult patients with mild to moderate Type 1 Gaucher disease, is now = approved=20 for the treatment of patients with NP-C. The NP-C indication was also = granted to=20 the following countries; European Union countries, = Australia, Korea, Brazil=20 and Russia. Regulatory proceedings to extend the use of = Zavesca^=AE in=20 patients with NP-C are ongoing in other countries worldwide.

About=20 Zavesca^=AE

In order to gain = approval=20 for Zavesca^=AE in Niemann-Pick type C disease, a set of = clinical data=20 were obtained from one clinical trial, OGT918-007, and two multicenter=20 retrospective cohort studies in patients with NP-C.

In the clinical trial OGT918-007, adult and juvenile patients with = NP-C=20 (n=3D29, age ≥ 12 years) were randomized to either miglustat 200 = mg t.i.d. (n=3D20)=20 or standard of care (n=3D9) for 12 months [1]. In addition, 12 children = aged 4-12=20 years received miglustat at a dose adjusted for body surface area. All = patients=20 were then given miglustat for another 12 months. Horizontal saccadic eye = movement (HSEM) velocity was the primary endpoint. Other endpoints = included=20 swallowing, ambulation, neurological examination, neuropsychological = assessment,=20 tremor and quality of life. At 12 months, HSEM velocity had improved in = patients=20 treated with miglustat versus those receiving standard care; in a post = hoc=20 analysis, which excluded patients taking benzodiazepines, known to = affect=20 saccadic eye movement velocity, results were significant (p=3D0.028) = [1]. Children=20 showed an improvement in HSEM velocity from baseline at 12 months. = Better=20 maintenance of swallowing and ambulatory functions were observed with = Zavesca=20 treatment versus those receiving standard care during the 12 month = controlled=20 study in patients older than 12 years [1].

A first retrospective cohort study was performed in 25 centers in 12=20 countries to assess data on changes of neurological status and overall = utility=20 of treatment with miglustat in 66 NP-C patients receiving miglustat = outside of=20 the clinical trial OGT918-007 for a mean duration of 1.5 years following = a mean=20 pre-treatment observation of 3.1 years. Disease progression was assessed = within=20 the functional domains swallowing, ambulation, manipulation=20 (dysmetria/dystonia), language function/articulation and overall = disability=20 according to a published NP-C disability scale. Across functional = domains and=20 for overall disability, ZAVESCA was associated with clinically relevant=20 reductions in annualized progression rate, compared with pre-treatment. = [1, 4].=20

A second retrospective cohort study was performed in 7 centers in 6 = countries=20 to assess data on changes in neurological status in 57 patients not = treated with=20 miglustat during the natural course of the disease for a mean duration = of 5.5=20 years. The same disease-specific disability scale was used to evaluate = the=20 severity of dysphagia, dystonia, ataxia and dysarthria at the time of = diagnosis=20 until the last visit.

Zavesca^=AE (100 mg miglustat capsule) is indicated for the = oral=20 treatment of adult patients with mild to moderate type 1 Gaucher = disease.=20 Zavesca^=AE may only be used in the treatment of type 1 = Gaucher patients=20 for whom enzyme replacement therapy is not a therapeutic option. It is = approved=20 in the European Union, the United States, Canada, Switzerland,=20 Brazil, Australia, Turkey and Israel.

Zavesca^=AE is indicated to slow the progression of some of = the=20 neurological manifestations in patients with Niemann-Pick type C = disease.

About Actelion

Actelion Ltd is a = biopharmaceutical=20 company with its corporate headquarters in = Allschwil/Basel, Switzerland.=20 Actelion's first drug Tracleer=AE, an orally available dual endothelin = receptor=20 antagonist, has been approved as a therapy for pulmonary arterial = hypertension.=20 Actelion markets Tracleer=AE through its own subsidiaries in key markets = worldwide, including the United States, the European Union, Japan, = Canada,=20 Australia and Switzerland. Actelion, founded in late 1997, is a leading = player=20 in innovative science related to the endothelium =96 the single layer of = cells=20 separating every blood vessel from the blood stream. Actelion's over = 2,300=20 employees focus on the discovery, development and marketing of = innovative drugs=20 for significant unmet medical needs. Actelion shares are traded on the = SIX Swiss=20 Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI = (Swiss=20 Market Index SMI^=AE)

References

1. Zavesca Product Monograph, March 3, 2010, Actelion=20 Pharmaceuticals Ltd.
2. Wraith JE, Imrie J. Understanding Niemann-Pick disease type = C and=20 its potential treatment. UK: Blackwell Publishing, 2007
3. Patterson MC. Niemann-Pick disease Type C. Gene = Reviews 2007a=20 (updated 9 July). Accessible at http://www.geneclinics.org/. = Accessed=20 October 2008.
4. Patterson MC, et al. Miglustat for treatment of = Niemann-Pick C=20 disease: a randomised controlled study. Lancet Neurol 2007; 6:765-772=20
5. Patterson MC. A riddle wrapped in a mystery: understanding=20 Niemann-Pick disease, type C. Neurologist 2003; 9:301-310.
6. Patterson MC, et al. Miglustat in Niemann-Pick disease Type = C=20 (NP-C): long-term data from a clinical trial. Proceedings of 58th = Annual=20 meeting of the American Society of Human Genetics, 2008; abstract # = 766.=20

For more information, please contact

Actelion = Pharmaceuticals Ltd -=20 Allschwil, Switzerland
Roland Haefeli
Vice President, Head of = Investor=20 Relations & Public Affairs
Office : +41 61 565 62 = 62
or
Actelion=20 Canada - Laval, Quebec
Marie-Claude Lefebvre
Medical = Director
Office :=20 450-681-1664

Click=20 here to see all recent news from this company

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Zavesca=AE (Miglustat) First Treatment Available in = Canada for Rare=20 Progressive Niemann-Pick Type C Disease

Zavesca^=AE (Miglustat) First Treatment Available in = Canada for Rare=20 Progressive Niemann-Pick Type C Disease