June 1, 2012 (Vol. 32, No. 11)
The highly fragmented pain-management market poses an opportunity for new classes of drugs targeting neuropathic pain as well as for generics as standard therapies come off patent. Because current therapies are often less than effective or have undesirable side effects, there also are emerging opportunities using genomics to match patients to pain medications.
Pain management today is dominated by Pfizer, Eli Lilly, Purdue Pharma, Endo Pharmaceuticals, Novartis, Johnson & Johnson, and Grünenthal. “Among these, Purdue Pharma, Endo, and Grünenthal specialize in pain,” points out Karen Holmes, senior market analyst and author of the recent Espicom Business Intelligence report, Evolution in the Pain Therapy Drugs Market: Nociceptive and Neuropathic Drug Development.
“Pfizer is by far the biggest player, consolidating its position with the acquisition of King Pharmaceuticals and Icagen. Including line extensions, Pfizer has at least 10 compounds in clinical development for pain indications.”
Whether those leaders will manage to maintain their positions depends upon how they manage their patent expirations as well as new drug development. “You have to be paranoid about the competition. The science isn’t stopping,” says John Steuart, managing partner, Claremont Creek Ventures. “Thousands of biotechs and tens of thousands of academic labs are working to develop new therapies all the time.” Pain management, he admits, is a mature market, so new therapies must be proven more efficacious or less toxic than existing medications.
Market projections vary, but Espicom estimated the global pain-management market at $46.4 billion at the close of 2011. The U.S. market accounts for 48% of that. Another market analyst, Global Industry Analysts (GIA), one year ago predicted the global pain-management market would reach $60 billion by 2015.
That predicted growth is based upon an aging global population, increasing number of surgeries, lifestyle changes, and a rising incidence of cancer. Some 1.5 billion of the world’s 7 billion people—21%—currently suffer from pain. That includes approximately 30% of all cancer patients and 60% of late-stage cancer patients.
The largest markets for pain-management medications currently are the U.S. and Europe. As with many pharmaceuticals, however, the fastest-growing markets are expected to be in Asia and Latin America, according to the GIA analysis, Pain Management: A Global Strategic Business Report. It anticipates a 9% compounded annual growth rate for pain-management therapies in Latin America between 2007 and 2015.
“Approximately 3 to 4.5% of the global population suffers from neuropathic pain,” according to GIA. Neuropathic pain is cited frequently as an important niche market, especially as blockbusters come off patent. It is a frequent side effect of cancer therapies, but also results from such metabolic disorders as diabetes, infectious diseases like HIV/AIDS or shingles (post-herpetic neuralgia), entrapment of a nerve (as in carpal tunnel syndrome), or demyelination in multiple sclerosis.
Existing first-line therapies for neuropathic pain include Pfizer’s Lyrica® and Eli Lilly’s Cymbalta®, Holmes says. “In addition to oral therapies, topical lidocaine is first-line therapy for localized peripheral nerve pain.” However, “Neuropathic pain is notoriously difficult to treat with current therapies.” In fact, few therapies are approved specifically for neuropathic pain.
“Of the 75 pain therapies currently in clinical trials, about 26 target neuropathic pain,” Holmes says. Of those, six specifically target post-herpetic neuralgia, while others target diabetic peripheral neuropathy, central neuropathic pain due to spinal cord injury or multiple sclerosis (MS), neuropathic pain in cancer, lumbosacral radiculopathy, and painful neuropathies affecting AIDS patients. Developers also are targeting nociceptive pain, including osteoarthritis pain and chronic low back pain, according to Espicom.
“Sales of novel treatments are unlikely to entirely replace the revenue lost following patent expiry of the current top five. However, there will be opportunities in underserved niche market segments, particularly neuropathic pain, which typically fails to respond adequately to conventional analgesics,” according to Holmes.
Grünenthal made its mark last spring with the European introduction of Palexia® (tapentadol), billed as “the first new molecular entity developed for the oral treatment of severe chronic pain to be introduced in the EU market in more than 25 years.” Janssen Pharmaceuticals, a Johnson & Johnson company, licensed the rights for the U.S., and markets it as Nucynta® and Nucynta ER®. It received FDA approval for the extended release formula last summer.
Tapentadol combines a mu-opioid agonist and a norepinephrine reuptake inhibitor in one molecule to provide opioid and non-opioid forms of pain relief. It reportedly has fewer side effects than oxycodone and other popular opioid pain relievers.
Another pain-management therapy, an 8% capsaicin patch called Qutenza®, was just approved in Wales for the treatment of peripheral neuropathic pain. It has been approved in Europe and the U.S. since 2009. Astellas Pharma in March withdrew its application for extended indications from the EMA. It is marketed in the U.S. by NeurogesX.
“Personalization of pain therapies based upon rational tools is more exciting than either the development of new targets or the presence of generics,” according to Steuart, at Claremont Creek Ventures.
AssureRx is developing a decision-support tool for psychologists to enable rational selection of pain products that are safe and effective and based upon patient’s individual genotypes. Approximately 40 psychotropic medications are being evaluated. The project is scheduled for a soft launch by early summer.
“In recent years, drug development in pain therapy has been focused mainly on reformulations of existing therapies and alternative modes of drug delivery to improve the delivery, safety, and efficacy of existing drug groups,” Holmes says.
For example, in March, Endo Pharmaceuticals acquired the Johnson Matthey patent for oxymorphone hydrochloride, extending patent protection for Endo’s entire oxymorphone franchise through 2029, including its new crush-proof tablets. Other drug developers are extending their brands through new indications. A look at Pfizer’s pipeline reveals 14 pain therapies in development, of which five are for new indications or enhancements.
Opioid analgesics form the largest single category of drugs in development, with a focus on formulations designed to reduce the risk of abuse. “Despite safety concerns, opioids remain the mainstay of moderate-to-severe pain therapy so it’s no surprise that several companies are developing potentially safer products,” Holmes says.
As the current market leaders go off patents, generic competition will become increasingly relevant. “The growth in the generic market is largely the result of the looming patent cliff,” Holmes says. “There already are tentative approvals from the FDA for generic versions of major sellers like Lyrica (pregabalin) and Cymbalta (duloxetine).
“A U.S. District Court has issued an order that prohibits the sale of generic duloxetine prior to patent expiry in June 2013, but it’s likely the generic market for this drug will be hotly contested,” she says. “We know of eight companies with tentative FDA approval for their generic versions of this product to date, and there are ongoing patent infringement actions with respect to Lyrica, which is currently patented in the U.S. to 2018.”
One strategy, Holmes says, is OTC switching—re-launching a former blockbuster for OTC use. When Novartis did this with Voltaren® (diclofenac) in 1999, the prescription brand continued strong sales in emerging markets because the brand was trusted, yet OTC sales hit $791 million in 2010.
“Generic drug makers are sitting pretty now,” Steuart says. A 2011 Supreme Court ruling effectively exempts generic manufacturers from liability, reasoning that under the Hatch Waxman Act (which authorized generics) they have no control over the information on their labels. “That eliminates a huge liability for generics manufacturers.”