Just a few weeks after NGX-4010 hit its primary endpoint in a pivotal HIV-associated sensory neuropathy trial, NeurogesX Inc. started the first of two Phase III studies to reduce pain for a different indication: postherpetic neuralgia.
At more than 50 U.S. sites, the San Carlos, Calif.-based company will evaluate NGX-4010 - its only product - in the two-arm, randomized, double-blind, controlled study. Researchers will determine how much the product reduces pain in postherpetic neuralgia (PHN) patients after a single application. NGX-4010 is a high-concentration trans-capsaicin dermal patch.
"Our product, capsaicin, is the ingredient in chili peppers that makes them pungent, spicy," said Anthony DiTonno, president and CEO of NeurogesX. "It works primarily, almost exclusively, in the epidermis, so the big advantage is it's non-systemic and you don't have any worries about systemic side effects."
The patch is designed to act where the pain frequently originates, as opposed to current treatments such as opioids that act on the central nervous system, and can cause drowsiness or constipation.
Half of the 400 PHN patients enrolled in the Phase III study will receive NGX-4010 for 60 minutes, while the other half will receive a control patch containing a low concentration of capsaicin for the same amount of time. Following treatment, patients will record their pain scores daily in personal diaries. The primary endpoint is the percent change in average pain level (0=no pain, 10=worst possible pain) from baseline to weeks two to eight.
Enrollment should be complete in the fourth quarter, and NeurogesX intends to start a second confirmatory Phase III trial later this year. Likewise, another Phase III study in the HIV-associated sensory neuropathy (HIV-AN) indication will begin before the end of the year. DiTonno said the company plans to submit one new drug application for both indications in the U.S. by the second quarter of 2007.
The PHN indication might be able to piggyback on the HIV-AN indication's fast-track and orphan drug status, which means approval for both could come before the end of that year. A filing in the European Union is expected somewhat earlier, in the second half of 2006, since Europeans do not require replicate trials
"The product so far is not partnered," DiTonno told BioWorld Today. "Right now, we are looking for a partner to commercialize the product outside the U.S."
As for the U.S. market, the company plans to build a specialty sales force of 75 to 100 people who will cover the 10,000 pain clinics that specialize in treating the conditions.
More than 2 million people in the U.S. and Europe suffer from either PHN, HIV-AN or another condition that NGX-4010 is targeting - painful diabetic neuropathy. The company has completed an open-label Phase II trial involving 92 patients with diabetic neuropathy, and findings were consistent with the other two indications. NeurogesX expects to start a Phase III trial in that indication in the first quarter of 2006. Diabetic neuropathy represents the largest market of the three indications.
"We've had outside market share estimates conducted for us that would suggest a peak revenue potential of the product in all three indications of about $700 million in the U.S. and $400 million in Europe," DiTonno said. "That would be seven years post-launch."
NGX-4010 has done well in clinical studies so far. The design for the new Phase III study in PHN follows positive data that came out of a 500-patient Phase II program, which demonstrated sustained neuropathic pain reduction from a single, one-hour dermal patch application. The treatment resulted in a 33 percent reduction in average pain scores, which were sustained for an average of 12 weeks.
And in May, NeurogesX reported Phase III results of NGX-4010 in HIV-associated sensory neuropathy. Those data, in 307 patients, showed a statistically significant pain reduction over a 12-week period following a single application of the drug.
Postherpetic neuralgia is a chronic, burning pain experienced by about 20 percent of people that heal from herpes zoster rash, or shingles. The market size is expected to increase with the aging population, since older people are more susceptible to shingles. HIV patients develop the condition 15 times more often than the general population.
In February 2004, privately held NeurogesX raised $35 million in a third financing round meant to cover the costs of NGX-4010's pivotal studies. (See BioWorld Today, Feb. 25, 2004.)
But the company likely will need to conduct another financing before the 2007 NGX-4010 NDA filing in the U.S.
"We have enough cash in the bank right now with a small round from our existing investors to take us to the next clinical milestone in the second quarter of 2006," DiTonno said.