Market Overview

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


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

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

In a clinical trial (OGT 918-007) where patients were given either 200 mg of Zavesca(R) three times a day (in pediatric patients the dose was 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 movement (HSEM) velocity (the ability to move eyes rapidly from side-to-side) in the Zavesca(R) treated group versus deterioration in the standard care group, and swallowing and ambulatory functions were better maintained.(4).

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

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

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

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

Zavesca(R) has been shown to be generally well tolerated in patients with NP-C, with the most common adverse events being - among others - diarrhea, weight loss and tremor (1, 4).

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

About Zavesca(R)

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

In the clinical trial OGT918-007, adult and juvenile patients with NP-C (n=29, age greater than or equal to 12 years) were randomized to either miglustat 200 mg t.i.d. (n=20) or standard of care (n=9) for 12 months (1). In addition, 12 children aged 4-12 years received miglustat at a dose adjusted for body surface area. All patients were then given miglustat for another 12 months. Horizontal saccadic eye movement (HSEM) velocity was the primary endpoint. Other endpoints included swallowing, ambulation, neurological examination, neuropsychological assessment, tremor and quality of life. At 12 months, HSEM velocity had improved in patients treated with miglustat versus those receiving standard care; in a post hoc analysis, which excluded patients taking benzodiazepines, known to affect saccadic eye movement velocity, results were significant (p=0.028) (1). Children showed an improvement in HSEM velocity from baseline at 12 months. Better maintenance of swallowing and ambulatory functions were observed with Zavesca treatment versus those receiving standard care during the 12 month controlled study in patients older than 12 years (1).

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

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

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

Zavesca(R) is indicated to slow the progression of some of the neurological manifestations in patients with Niemann-Pick type C disease.

About Actelion

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, the European Union, Japan, 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's over 2,300 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI(R) )


-- 1. Zavesca Product Monograph, March 3, 2010, Actelion Pharmaceuticals

-- 2. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its
potential treatment. UK: Blackwell Publishing, 2007

-- 3. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a
(updated 9 July). Accessible at Accessed October

-- 4. Patterson MC, et al. Miglustat for treatment of Niemann-Pick C
disease: a randomised controlled study. Lancet Neurol 2007; 6:765-772

-- 5. Patterson MC. A riddle wrapped in a mystery: understanding Niemann-
Pick disease, type C. Neurologist 2003; 9:301-310.

-- 6. Patterson MC, et al. Miglustat in Niemann-Pick disease Type C (NP-C):
long-term data from a clinical trial. Proceedings of 58th Annual meeting
of the American Society of Human Genetics, 2008; abstract # 766.

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