Ariel Pharmaceuticals focuses major unmet medical needs where there are hard clinical endpoints that can be demonstrated in clinical trials of relatively short duration. Our markets are characterized by having little competition but large unmet medical needs.
The prostanoid EP4 receptor has been shown to play a significant role in a number of diseases where prostaglandin E2 is involved. These range from orphan diseases such as Familial Adenomatous Polyposis (FAP) to neurodegenerative diseases like Multiple Sclerosis and to major diseases involving pain and/or inflammation. Among these wide-ranging clinical indications Ariel is pursuing development of our lead product, AP-1531, in the following areas:
Episodic migraine headaches affect 10-20% of the world population and are among the top four disabling neurological conditions (WHO). Migraines account for an estimated 30 million days of lost productivity at a cost of up to $17 billion per year in the US. Approximately half of migraine patients suffer severe pain and require bed rest. Migraines affect 28 million Americans; one of every four American households has a family member who suffers from migraine headaches (American Headache Society). At present, the most common migraine therapies are non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (5-HTIB/1D agonists). Sales of these drugs total $4 billion worldwide, with triptans comprising $2.7 billion of this total. Shortcomings of currently available drugs include slow speed of activity (up to 90 minutes for market leader Imitrex), recurrence of pain, and debilitating side effects, including cardio- and GI toxicity.
Osteoarthritis (OA) is the most frequent chronic joint disease causing pain and locomotor disability of especially the hip, hand and knee. Patients with OA have pain that can fluctuate with physical activity, e.g., worsening with weight bearing and improving with rest. OA affects nearly 21 million people in the US, accounting for 25% of visits to primary care physicians, and it costs our economy approximately $60 billion per year. The most common treatments for pain, one of the most common symptoms, include acetaminophen, NSAIDs and COX inhibitors. NSAIDs and COX inhibitors are widely prescribed, potent pain relievers but have side effects and are contraindicated in many OA patients who are often over the age of 60 with cardiovascular co-morbidities. The US market opportunity for new OA drugs could be significant with the patent expiration of Celebrex in 2014 and the relatively modest number of competing drugs undergoing clinical development for OA pain relief.
The incidence of cancers has been declining in the US by about 1% per year (CDC). However, cancer mortality is still a significant cause of death in this country. In the US there are about 600,000 newly diagnosed cases of lung, breast and colorectal cancer (CRC) per year and about 250,000 deaths. One contributor to the continuing significant death rate in some cancers has been resistance to treatment that is often due to genetic mutations. For example the efficacy of Erbitux and Tarceva in treatment of breast cancer is limited in the presence of mutations to the EGFR receptor, and 40% of CRC patients have a mutated RAS gene that makes them unresponsive to conventional therapy. Numerous studies have shown that prostaglandin E2 and the EP4 receptor play a significant role in colorectal tumor growth and metastasis, and invasion/metastasis in breast and lung cancers. EP4 receptor antagonists like AP-1531 have great promise as a single agent or combination product for treatment-resistant cancer patients.