JAK and Ion Channels
Pfizer’s JAK inhibitor has had better luck in treating arthritis pain. Pfizer reported that tasocitinib significantly reduced the signs and symptoms of moderate-to-severe rheumatoid arthritis (RA), a primary endpoint. The drug, administered as monotherapy, also improved physical function versus placebo at three months. The drug did not meet a third primary endpoint of disease remission.
Another well-informed bet on a completely different kind of pain drug comes in the form of Icagen’s ion-channel modulators. On November 30, the partners reported that Nav1.7 was chosen to progress into Phase I trials. Richard Katz, M.D., Icagen’s CFO, says that the timeline for starting the Phase I trials will be up to Pfizer but thinks that they will begin either this year or early in 2011.
Icagen gained 96 cents a share to close at $2.18, up more than 75%, on the news. It also garnered a $1 million milestone payment from Pfizer.
Pfizer and Icagen are targeting three specific sodium ion channels for the treatment of pain and related disorders. This November the companies extended their agreement for an additional 15 months until December 2011, with Pfizer continuing to fund all R&D costs. Icagen could receive up to $359 million in research, development, regulatory, and commercialization milestones for each product, in addition to royalties on future sales.
Dr. Katz told GEN that NAV1.7, an ion channel that plays an important role in the detection, transmission, and cognitive recognition of pain signals, may provide a unique target for pain medication. “The NAV1.7 ion channel has been genetically linked to congenital indifference to pain.”
In 2006, he said, a research paper in Nature described a rare autosomal-recessive disorder, clinically characterized by insensitivity to all modalities of pain except neuropathic pain, in which recurrent injuries frequently go unnoticed. The disorder is linked to mutations in the SCN9A gene which encodes the alpha subunit of the NA1.7 ion channel, strongly expressed in nocioceptive neurons.
Icagen has been working on ion channels as potential novel drug targets for several years, Dr. Katz told GEN. “There are no drugs that work through this mechanism except Lidocaine, which acts as a nonspecific NAV blocker but can’t be used systemically. We have been working to identify this and other selective molecules that we believe are important in the transmission of pain signals.”