ALS: a disease without a treatment?

Although the prevalence of ALS is not very high, this progressive neurodegenerative disease is not as rare as initially thought. The area is also critically underserved with only one approved drug, which has numerous side effects. Although the patient population for ALS is small, the disease presents companies with a variety of opportunities, from off-label use of marketed products to new drugs for use in a host of indications.

Amyotrophic lateral sclerosis (ALS) is one of many orphan diseases in the CNS arena. With Aventis' Rilutek the only prescription drug currently approved for this indication, the area has suffered from minimal attention.

The disease works by attacking and destroying motor neurones. As the muscles receive fewer impulses from the motor neurones, they eventually weaken and atrophy. Death often occurs as a result of respiratory failure usually within three years of perception of first symptoms. ALS is also known as Lou Gehrig's disease in the US, Maladie de Charcot in France and Motor Neurone Disease (MND) in the UK.

Measures needed for progress

Datamonitor opinion leader research has identified a need for standardization of disease definition and accurate diagnostic tests in order to increase the revenue potential of this market. Up to 45% of ALS patients are given at least one misdiagnosis before definitive identification is made, thus highlighting the importance of educating physicians.

Pharmaceutical companies must aid this process by conducting trials in conjunction with patient foundations such as the ALS Therapy Development Foundation in the US. This would increase awareness of their product as well as help build relationships with neurologists.

The risks facing pharmaceutical companies should be reduced by the fact that orphan drug research is subsidized by regulatory authorities across the seven major markets. This provides smaller biotechnology companies with the opportunity to increase revenues as well as increasing the possibility of collaborating with larger firms.

Additional incentives would bring the involvement of leading pharmaceutical companies hoping to expand their CNS franchises. This would also help increase awareness of ALS as large companies have the resources to implement national awareness campaign initiatives.

Only Rilutek

Aventis' Rilutek (riluzole) is the only prescription drug currently approved for the treatment of ALS, although opinion leaders and physicians doubt its true therapeutic value.

On average, Rilutek increases survival by only three months. However, reports have shown that the probabilities of survival are greater in the first 15 months of treatment. Rilutek is generally well tolerated among patients but as it does not treat the symptoms nor delay the onset of the disease, other therapies are required. As a result, symptomatic treatments feature quite heavily in the management of ALS.

Nevertheless, Rilutek sales topped $100m in 2002, demonstrating that significant commercial opportunities exist despite low patient numbers. Companies could also look to develop drugs for the treatment of ALS with a view towards approval for more lucrative indications such as Alzheimer's disease (AD).

Several clinical trials to assess efficacy have revealed confusing or negative data with both new and approved drugs. Datamonitor believes that this may be due to problems with trial designs or the anticipation of an outstanding effect. Rilutek was barely approved due to differences in statistical analyses. An improvement in the design of clinical trials will allow more effective drugs to be developed.

A limited pipeline

At present the main unmet needs in the treatment of ALS is for a treatment that slows the progression of the disease. A better understanding of the disease would aid this but as yet the causative factors of the disease remain unclear.

The lack of approved ALS therapies suggests that once approval is gained neurologists will be keen to prescribe such drugs. Physicians recognize the commonalities between neurodegenerative disorders such as AD and Parkinson's disease, a similarity that may aid off label use of ALS drugs for other neurodegenerative diseases.

There are meanwhile, other drugs on the horizon that could offer hope for ALS patients. If Pfizer is successful in expanding the indications for Celebrex, other COX-II inhibitors are likely to be investigated in this area. Wyeth's Minocin was recently found to delay the onset of symptoms of ALS by up to several weeks and other compounds, such as Novartis' TCH-346 lie in the middle of clinical development.

Breakthrough required

Without the future market entry of effective drugs, physicians hope to treat ALS in five to ten years time using a cocktail of drugs.

Finding a cure to ALS may be a long way off but pharmaceutical manufacturers can aid patients and doctors in improving care post diagnosis. Other areas to target are not necessarily treatment related but diagnostic. There is chronic lack of diagnostic tools or biomarkers, which could aid the diagnosis of ALS.

When ALS is better understood and more effectively diagnosed, pharmaceutical companies will be more willing to investigate possible treatments. Until then, Aventis' Rilutek will remain as the only drug available for the direct treatment of ALS.

If you found this week's Expert View useful, you may be interested in Datamonitor's reports:

• Amyotrophic Lateral Sclerosis: A route to larger CNS markets? priced $1,600
• Movement Disorders: Niche Markets Offering Commercial Opportunities For Smaller Manufacturers priced $1,500
• Benchmarking Blockbusters: Identifying winning products and therapy areas to 2008 priced $6,400

To order these reports contact support@bioportfolio.com or telephone +44 1300 321501 or +1 415 680 2472 and a representative will get back to you.