West Coast Editor
About two weeks after reporting that its non-opioid pain drug, ALGRX 4975, worked in a Phase II trial against tendonitis of the elbow, Corgentech Inc. said the compound did not meet statistical endpoint in a study against pain from groin hernia surgery.
The company’s stock (NASDAQ:CGTK) closed Monday at $8.70, down 34 cents. Company officials could not be reached, but Keith Bley, senior vice president, nonclinical research & development for NeurogesX Inc., of San Carlos, Calif. - which also has a program in the same area but with a topical drug - said he would not call the Corgentech outcome a failure.
"Because of the other medications [given to the patients in the study], their overall pain signal was just too low," he told BioWorld Today.
The 41-patient European study measured the drug’s effect one and four weeks after surgery, with patients given either a single dose of 4975 or placebo, which was instilled (dripped by syringe) into the wound for about a minute before wound closure.
All patients in both the treatment and placebo arms got paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (ibuprofen) for a week after surgery, which is a mandated standard of care in Denmark, where the trial was conducted - and might have blunted evidence that South San Francisco-based Corgentech’s drug worked, particularly in that first post-surgical week, when pain typically is the most intense.
No significant difference in relief showed up in the treatment arm vs. the control arm.
Earlier this month, Corgentech offered positive data from the tendonitis Phase II study, showing the 45-patient trial met its primary endpoint of response to ALGRX 4975 in treating pain induced by wrist dorsiflexion, four weeks after patients were treated with a single injection of ALGRX 4975 or placebo. At week four, 64 percent (14 of 22) of patients treated with ALGRX 4975 were considered responders, vs. 30 percent (seven of 23) of patients treated with placebo (p=0.0256).
A vanilloid-1 receptor (VR1) agonist based on capsaicin, ALGRX 4975 acts as a C-neuron anesthetic and became part of Corgentech’s pipeline in the merger, completed last December, with AlgoRx Pharmaceuticals Inc., of Seacaucus, N.J. (See BioWorld Today, Sept. 27, 2005.)
Capsaicin gives chili peppers their heat, and plant extracts have been used as topical pain treatments for centuries. The hernia-surgery trial is one in a series of Phase II studies, which have shown significant pain reduction not only in elbow tendonitis, but in patients undergoing bunionectomy and those with the neuropathic foot condition known as Morton’s neuroma.
Phase II trials with the compound in total knee replacement and cholecystectomy have completed enrollment, with data due in the second quarter of this year.
NeurogesX’s compound targeting what should more specifically be called the transient receptor potential vanilloid 1 receptor, or TRPV1, is NGX-4010, a high-concentration form of synthetic capsaicin, known as trans-capsaicin, applied directly to the site of pain via a rapid-delivery dermal application system. Near the end of last year, the specialty pharma firm raised $20 million through a private equity financing to wrap up pivotal trials with the product, branded Transacin, in HIV-associated neuropathy and postherpetic neuralgia. (See BioWorld Today, Dec. 5, 2005.)
Bley said lower-concentration forms of capsaicin for topical use are available, but they sting, and require multiple applications, so patience compliance is poor.
"We have a single intermittent procedure, performed in a health care provider’s office," he said, adding that capsaicin might be useful against "a whole host of other" conditions, such as psoriasis.
Allan Basbaum, professor and chairman of the anatomy department at the University of California San Francisco, is considered an expert on TRPV1. He has served as an adviser to NeurogesX and is editor-in-chief of the journal Pain.
"Objectively, it’s a failure," he said of the Corgentech trial. "It’s kind of a surprising choice," he added, regarding the post-operative hernial pain indication - and showing efficacy when other drugs are being used is particularly hard.
The other indications "make more sense," he told BioWorld Today.
Also working to develop pain drugs that target the VR1 receptor is Branford, Conn.-based Neurogen Corp., which has a major deal with Merck & Co. Inc., of Whitehouse Station, N.J., entered in late 2003. The firms in February started Phase I trials with NGD-8243. (See BioWorld Today, Dec. 2, 2003.)
In that collaboration, Merck made a $15 million license fee payment to Neurogen and bought $15 million of Neurogen stock, agreeing to pay $12 million in research funding and license maintenance payments, with another $118 million possible in milestone payments.
South San Francisco-based Renovis Inc. has a pharma-backed VR1 pain program, as well. In May, the firm entered into a $187 million preclinical research deal with New York-based Pfizer Inc. (See BioWorld Today, June 1, 2005.)