Pain is an underserved market because the use of opioid agonists to treat moderate to severe pain is limited by common side effects like grogginess and constipation, the development of tolerance and dependence, and the potential for abuse. Thus, there has long been an obvious need for effective and non-addictive alternatives. Yet of the more than 80 companies working on pain therapeutics, most are simply developing new formulations of old opioid agonists like morphine, oxycodone and fentanyl.
The reason so many companies are working on new formulations is simple: improved formulations still constitute low-hanging fruit. New strategies for administering opioid agonists may be able to alleviate some side effects while creating novel intellectual property.
By contrast, there are no good treatments for neuropathic pain, which involves actual damage to the peripheral and central nervous systems. Increased knowledge of ion channel sub-types is now offering opportunities to develop more specific compounds that overcome the shortcomings of earlier drugs. And some companies are hoping ion channel blockers may find applications in treating inflammatory pain. But most of these efforts are still years away from the market.
"If you look back just about 15 years, many companies didn't see much opportunity in developing new drugs to treat pain," said Bill Schmidt, vice president of scientific affairs at Adolor Corp. (ADLR, Exton, Penn.), and author of the recently published book Pain: Current Understanding, Emerging Therapies, and Novel Approaches to Drug Discovery.
Indeed, he said that with the exceptions of Ultram tramadol, an opioid agonist marketed in the U.S. by Johnson & Johnson (JNJ), and the COX-2 inhibitors, "there really haven't been any new chemical entities released for about 20 years."
The reasons are two-fold. First, the practice of pain treatment was not as well understood as it is today, and thus the value of longer acting drugs was not fully appreciated. Second, research has only recently identified new targets such as specific ion channel sub-types, of which about 12 are in the clinic.
"Pain today is perhaps where depression was 40 years ago," said Remi Barbier, CEO of Pain Therapeutics Inc. (PTIE, South San Francisco, Calif.). "Everyone is aware that there is this thing called pain, but no one dies from extreme pain. On the other hand, it absolutely destroys lifestyle. Patients quit eating, they lose weight, they get depressed."
"Pain costs over $100 billion a year - before the costs of pain medication - in lost efficiency," according to Ken Koblan, executive director of molecular pharmacology at Merck & Co. Inc. (MRK, Whitehouse Station, N.J.). "In the U.S. alone, there are 40 million people suffering from chronic headaches, 35 million from persistent back pain and 5 million from cancer pain."
There are a further 193 million cases of acute pain each year, according to Ionix Pharmaceuticals Ltd. (Cambridge, U.K.). The company estimates that more than $22 billion was