Irena Melnikova

Therapies for Alzheimer's disease

Alzheimer’s disease (AD) is a devastating neurological disorder that affects more than 37 million people worldwide1. The economic burden of AD is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least US

Rare diseases and orphan drugs

100 billion. However, the number of therapeutic options for AD remains severely limited. Currently marketed drugs for AD do not prevent or reverse this disease and are approved only for the management of symptoms. Driven by the clear unmet medical need and a better understanding of the biology and pathophysiology of AD, the number of drugs in development for this indication has increased dramatically in recent years.

Targeting protein kinases

Rare diseases affect, by definition, only a small number of people. This article investigates how drug development for rare diseases can provide attractive opportunities for biopharmaceutical industries.

The anticoagulants market

Abstract Protein kinases are considered to be the second most important group of drug targets after G-protein-coupled receptors1, 2. Aberrant kinase activity is implicated in a variety of human diseases, in particular those involving inflammatory or proliferative responses, such as cancer, rheumatoid arthritis, cardiovascular and neurological disorders, asthma and psoriasis.

Hepatitis C therapies

Thrombosis — localized blood clot formation — is a leading cause of morbidity and mortality associated with arterial diseases, such as myocardial infarction and stroke, and venous thromboembolic (VTE) disorders, including deep vein thrombosis and pulmonary embolism1. VTE is the third leading cause of cardiovascular-related death, after myocardial infarction and stroke, and is one of the leading causes of death in patients with cancer. Antithrombotic drugs, including anticoagulants, antiplatelet agents and direct thrombolytics, are used for both the prevention and the acute treatment of thrombosis1 (TABLE 1). Anticoagulants target elements of the coagulation cascade (FIG. 1) and are typically used for shortand long-term management of thrombotic disorders of both the arterial and venous systems. The most common use of anticoagulation is for stroke prevention in patients with atrial fibrillation (TABLE 1).

Hepatitis C — pipeline update

Hepatitis C virus (HCV) is the major cause of liver disease worldwide and a potential source of high morbidity and mortality in the future. The World Health Organization estimates that approximately 170 million people, 3% of the world’s population, are chronically infected with HCV, and 3–4 million new infections occur each year. According to the Centers for Disease Control and Prevention, over 3 million people have chronic HCV in the US, and the current annual rate of infection is around 30,000. The current standard of care for HCV is a combination of PEGylated–interferon (PEG–IFN) and ribavirin. PEG-IFNs available on the market include PEG–Intron (Schering–Plough) and Pegasys (Roche). Marketed ribavirin includes Rebetol (Schering–Plough), Copegus (Roche) and various generic versions. The overall clinical success rate, referred to as sustained virological response (SVR), of this combination therapy is only around 50%1. The treatment is lengthy (48 weeks for genotype 1 HCV) and associated with frequent and sometimes serious side effects including neuropsychiatric events, flu-like symptoms and haematological toxicities. It is also contraindicated for many patients1. Overall, it is estimated that only 10% of patients with chronic HCV are successfully treated with the current standard of care.

Future of COX2 inhibitors.

Over 3% of the world’s population is chronically infected with hepatitis C virus (HCV). Chronic hepatitis C (CHC) is a major cause of liver damage, cirrhosis and liver cancer that can lead to liver failure and death. The current standard of care (SOC) is a combination of pegylated interferon with ribavirin (PEG-IFN/RBV), but this only eradicates the virus in approximately 50% of patients1. The recently concluded sixty-first annual meeting of the American Association for the Study of Liver Diseases (AASLD) provided a broad overview of the pipeline of novel drugs for the treatment of CHC2. It is clear that this field is on the brink of significant improvements to the SOC that should follow the highly anticipated approval of the first direct antiviral agents (DAAs), telaprevir (Vertex/Johnson & Johnson/Mitsubishi) and boceprevir (Merck), in 2011.

Wet age-related macular degeneration

In the 1990s, a new class of drugs collectively known as selective inhibitors of cyclooxygenase 2 (COX2) was developed for the treatment of pain and inflammation. Selective COX2 inhibitors (coxibs) were designed to be at least as efficacious as the common non-steroidal anti-inflammatory drugs (NSAIDs), but to lack one of their major side effects, gastrointestinal (GI) bleeding (Table 1).

Raising HDL cholesterol

Wet age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. It results from the growth of abnormal leaky blood vessels beneath the macula that eventually damage the area of the eye responsible for central vision, which is essential for most fine-detail visual activities, including reading, driving and recognizing faces. In the US, an estimated 1.6 million adults over the age of 50 suffer from wet AMD and about 200,000 new cases are diagnosed annually. Worldwide, approximately 500,000 new cases of wet AMD are diagnosed each year. With only one drug indicated for the disease until just recently, the market for wet AMD therapeutics remains largely untapped. As a vision-threatening disease that affects a rapidly growing ageing population, AMD represents a considerable market opportunity for novel therapeutics1.

Apoptosis-targeting therapies.

NATURE REVIEWS | DRUG DISCOVERY VOLUME 4 | MARCH 2005 | 185 Reducing serum levels of low-density-lipoprotein cholesterol (LDLc) remains one of the primary therapeutic approaches of lowering the risk of coronary disease. However, more than one-third of patients with coronary disease have normal LDLc levels, but low levels of highdensity-lipoprotein cholesterol (HDLc) (less than 35 mg per dl). Low HDLc levels are strong, independent predictors of cardiovascular disease (CVD) and represent a mortality risk for both men and women. Recent epidemiological, experimental and clinical-trial data indicate that a 15 mg per dl rise in HDLc would reduce coronary artery disease incidence and mortality by 30–70%. Although statins have proven to be highly effective at lowering LDLc, their ability to raise HDLc is limited. For patients with low HDLc as the predominant lipoprotein abnormality, fibrates or nicotinic acid are recommended as alternatives to statin therapy. Unfortunately, sub-optimal safety profiles limit the usefulness of these drugs. Alternative therapies for raising HDLc are being developed.