Botox, a botulinum toxin injection that paralyzes the underlying muscle, is undergoing Phase III trials for back pain (Europe
and United States) as well as Phase II trials for migraine (United States) and tension headache (Canada, Europe, and United
States). Although there are some novel drugs in development, most pipeline pain therapeutics are opioids and NSAIDs, which
often are reformulations of products with advanced delivery systems. Therefore, new classes of drugs in the pain-management
segment are limited. (See "Soon to Launch,".)
Soon to Launch : Heres a sampling of new drugs (or indications) that should be approved in the next four years.
Ronald Burch, MD, PhD, the CEO and founder of AlgoRx, explains why there are so few advances in pain management. "Pain was
the first accomplishment of pharmacology, with aspirin and opiates," he says. "Therefore, little research [in this area] has
been done over the last 30 years. There is more emphasis on delivery than on novel mechanisms of action."
AlgoRx is an emerging pharma company that is focused on developing products to treat pain. It has two lead products in development.
The first, ALGRX 4975, is an injectable capsaicin. The compound, which is what makes chili peppers taste hot, is already used
in some topical analgesics. Its second project, ALGRX 3268, is a dermal lidocaine that uses powderject technology.
Adolor is another company with a novel pain approach. Its pipeline projects target kappa opioid receptors located outside
the brain rather than the mu receptors targeted by most opioid drugs, thus minimizing side effects. Adolor's Entereg (alvimopan)
is under FDA review for the treatment of postoperative ileus, a painful bowel condition caused by excessive use of opioids.
Advances in pain management are not limited to new drug classes or indications, but can be seen in the many ways that treatments
On the market. One widely prescribed alternative delivery system in the pain market is Johnson & Johnson's Duragesic (fentanyl patch). A
single patch provides pain relief for up to three days for patients with moderate to severe chronic pain, such as cancer
pain. The patch's ease of administration makes it a preferred choice among physicians, caregivers, and patients because it
increases patient compliance and convenience.
Another product allowing for easy administration is Cephalon's Actiq (oral transmucosal fentanyl citrate), nicknamed the "fentanyl
lollipop." Approved in 1998, Actiq is the only drug indicated for the management of breakthrough cancer pain in patients already
on an around-the-clock opioid regimen. It is particularly beneficial to patients with reduced swallowing control because of
its titratable dosing feature. Generating more than $237 million in 2003 revenues, prescriptions for Actiq will gradually
increase as more physicians and patients become comfortable using the product.
According to physicians who participated in Navigant Consulting's Cancer Pain Physician Survey, Duragesic is especially important
for cancer patients because they often have trouble ingesting medication. Consequently, it is the most commonly prescribed
long-acting opioid among surveyed oncologists and pain specialists.
The survey also found that physicians who are most likely to prescribe Actiq are specialists in oncology/hematology practicing
at cancer centers and universities, and those less likely to prescribe Actiq are general oncologists. This may be attributable
to oncologists' higher level of comfort with traditional injectable short-acting narcotics.
In the pipeline. Many more novel drug delivery systems are now in the near-term pipeline. (See "New Delivery Pipeline," .) Some candidates
combine common generic compounds with novel technologies. Others, such GW Pharmaceuticals' Sativex are both a new drug and
a new delivery system (oral mucosal spray).
New Delivery Pipeline : This sample of technologies in development use effective, off-patent compounds and deliver them to
patients in novel, often fast-acting ways.
Duragesic's growing popularity since its launch in 1991 has encouraged the entry of even more advanced patch technologies.
To provide patients with an alternative to intravenous (IV) opioid relief as they recover from surgery, Alza (a subsidiary
of J&J) is coupling its E-TRANS electrotransport technology with fentanyl, a standard opioid, to treat acute postoperative
pain. While Duragesic is based on Alza's D-TRANS system, which incorporates layers of thin, flexible films, the new E-TRANS
fentanyl's platform is more technologically sophisticated. Battery and button operated, the iontophoretic system applies a
low-level electrical current for rapid, consistent, patient-controlled transdermal delivery. In July, FDA issued Alza an
approvable letter for the product.