Impax Pharmaceuticals said today it will end co-development with GlaxoSmithKline of IPX066 outside Taiwan and the U.S., where the Parkinson’s disease drug candidate is called Rytary™, three months after FDA issued a complete response letter tying approval to reinspection of a manufacturing plant cited by the agency in 2011.
FDA’s complete response letter, issued in January, stated that the agency would not approve Impax’ NDA for IPX066 absent reinspection of Impax’ Hayward, CA, manufacturing facility. The facility was cited in a 2011 FDA warning letter to Impax for failure of certain batches to meet specifications deviations as well as deviations from current Good Manufacturing Practice (cGMP) for finished pharmaceuticals related to sampling and testing of in-process materials and drug products, as well as production record review.
Impax responded to the 2011 letter first by a voluntarily recall of five lots of Fenofibrate capsules (200 mg), then by taking corrective actions following a review of its manufacturing systems and standards—as well as by withdrawing Hayward as an alternate production site. Impax last year substantially completed an expansion of its Taiwan manufacturing plant, saying at the time that a "major portion" of the added work envisioned as being production of IPX066.
However, because the site was previously involved in development of IPX066, FDA requires that issues it raised in the warning letter be addressed.
"The decision has been reached because of delays in the anticipated regulatory approval and launch dates in countries in which GSK has rights to commercialize the product,' Impax said in a statement.
IPX066 is an extended-release capsule formulation of carbidopa-levodopa indicated for symptomatic treatment of adult patients with idiopathic Parkinson’s disease. Under an agreement the companies signed in December 2010, the right to develop and commercialize the drug outside the U.S. and Taiwan will transfer back from Glaxo to Impax effective at the end of July 2013.
"Impax intends to initiate activities to find a partner or partners for markets outside the U.S. looking to grow their non-U.S. neurology franchise," the company stated.
The 2010 agreement called for Impax to manufacture and supply IPX066 to GSK. In return, GSK paid Impax $11.5 million up-front in December 2010, and agreed to pay up to an initially announced $175 million tied to successful achievement of development and commercialization milestones. Impax was also supposed to have received tiered, double-digit royalty payments on GSK sales of IPX066.
By the time Impax filed its 10-K annual report for 2012 with the U.S. Securities and Exchange Commission on February 26, the company stated its milestone payment potential at $169 million—of which $10.0 million was contingent upon the achievement of unspecified clinical events, $29.0 million contingent upon the achievement of unspecified regulatory events, and $130.0 million upon the achievement of unspecified commercialization events.
"Based upon our current anticipated development timeline for IPX066, we believe we may receive the next milestone payment under this agreement in the amount of $24.0 million during the fiscal year ending December 31, 2013, which is contingent, however, on our achievement of a certain specified regulatory milestone event," Impax said in its Form 10-K.
Impax submitted a New Drug Application for IPX066 to FDA in December 2011, including in part results from three controlled Phase III studies and two open label extensions of IPX066 in early and advanced Parkinson’s disease. A combined 900 patients with the disease took part in the studies and extensions. One of those studies, ASCEND-PD, showed that patients treated with IPX066 showed a 33.5% decrease in "off time" during waking hours—from 5.9 hours to 3.8 hours—compared with a 10% decrease or 5.2 hours for CLE treatment.
Impax Pharmaceuticals—the branded-drugs division of Impax Laboratories—focuses on targeting significant unmet needs, primarily the development of treatments for central nervous system disorders.