West Coast Editor
With a new oral form of methylnaltrexone (MNTX) for opioid-induced constipation in the works, Progenics Pharmaceuticals Inc. and partner Wyeth Pharmaceuticals submitted, on schedule, a new drug application for the subcutaneous version.
Approval could come early next year, and the firms plan to add data during the review period that would support shelf life of up to 18 months for room temperature-stable, single-use vials. Pre-filled syringes would be introduced later in 2008.
"The nice thing about the subcutaneous [version] is that it's essentially laxation on demand," noted Richard Krawiec, Progenics' vice president of corporate affairs. Opioid analgesics, given for pain in advanced illness, constipate almost every patient, and no drug exists specifically for that population.
"We started in patients receiving palliative care because that was the largest unmet medical need," Krawiec said, but the companies plan to expand into other populations later. MNTX mitigates the effect of opioids on peripheral receptors without interfering with their action in the brain. The compound has shown strong results in two Phase III trials.
"It shouldn't be considered a laxative," Krawiec said, adding that laxatives and stool softeners are ineffective in opioid-induced constipation because they do not induce gastrointestinal contractions. "Without peristalsis, you can give all these stimulants and nothing happens," he said.
Oncology patients on opioids may find that the pain from constipation becomes worse than the cancer pain - so they take more opioids, and make the situation worse.
Early last month, Progenics and its partner, a division of Madison, N.J.-based Wyeth, started clinical testing of a new form of oral MNTX after the preliminary data from a Phase II trial with the initial form.
"The idea is to create a continuum, so the physician can match the form of [MNTX] to the condition," Krawiec said. "I can see people presenting at the doctor's office and taking the subcutaneous form, and then switching to the oral form at home eventually." The subcutaneous form could be used while traveling, and for laxation relief in the morning.
There's also an intravenous version of MNTX in Phase III trials for postoperative ileus (bowel impairment after surgery). Data are expected in the fourth quarter of 2007.
Progenics signed the potential $416 million Wyeth deal in late 2005, at the same time buying back royalty rights to MNTX from UR Labs Inc., which acquired the drug from the University of Chicago before licensing it to Progenics in October 2001. Progenics agreed to pay UR $2.6 million in cash plus 686,000 shares in the deal.
Lazard Capital Markets forecast $59.2 million in 2008 sales of subcutaneous MNTX, with the amount reaching $455.2 million in 2010.
Ahead for Progenics are Phase Ib data with the HIV therapy PRO-140, expected in the second quarter of this year. Last December, the company completed enrollment and dosing with the humanized monoclonal antibody, a viral entry inhibitor. The study involves 39 HIV-infected patients who had not received any antiretroviral therapy within the previous three months and who had HIV plasma concentrations of 5,000 copies/mL or more.