The United States Food and Drug administration has granted fast track designation to Isis Pharmaceuticals' ISIS-TTRRx for the treatment of familial amyloid polyneuropathy (FAP).  

ISIS-TTRRx is an antisense drug in development with GlaxoSmithKline (GSK) for the treatment of transthyretin (TTR) amyloidosis, a severe and rare genetic disease characterized by progressive dysfunction of peripheral nerve and/or heart tissues.  Isis and GSK recently amended the clinical development plan and financial terms relating to ISIS-TTRRx to support a registration-directed phase 2/3 clinical study on ISIS-TTRRx, which is expected to start this month.

"We are pleased to have received orphan drug status and fast track designation for ISIS-TTRRx for patients with FAP.  ISIS-TTRRx is our most advanced drug from our severe and rare disease franchise and represents a significant near-term commercial opportunity for us," said B Lynne Parshall, chief operating officer and chief financial officer at Isis.  "We look forward to continuing to move ISIS-TTRRx toward the market for patients who have very limited therapeutic options."

ISIS-TTRRx is part of the Isis-GSK strategic alliance to develop RNA therapeutics for rare and infectious diseases.  Upon initiation of the phase 2/3 study, Isis will receive a $7.5 million milestone payment and is eligible to earn an additional $50 million in pre-licensing milestone payments to support the phase 2/3 study of ISIS-TTRRx­.  In addition, Isis is eligible to receive regulatory and sales milestones and double-digit royalties on sales of ISIS-TTRRx.

Transthyretin amyloidosis is a genetic disease in which the patient inherits a mutant gene that produces a misfolded form of TTR, which progressively accumulates in tissues, impairing their function.  In patients with transthyretin amyloidosis, both the mutant and normal forms of TTR can build up as fibrils in tissues, including heart, peripheral nerves, and the gastrointestinal tract.  The presence of TTR aggregates interferes with the normal functions of these tissues, and as the TTR protein aggregates enlarge more tissue damage occurs and the disease worsens.  

There are two common types of transthyretin amyloidosis, familial amyloid cardiomyopathy, or FAC, which affects more than 40,000 patients worldwide, and FAP, which affects more than 10,000 patients worldwide.  Patients with FAC have TTR build up in the heart muscle and succumb to heart failure five to six years after symptom onset.  Patients with FAP have TTR build up in peripheral nerve tissue leading to the loss of nerve function and wasting.  ISIS-TTRRx is an investigational drug that is designed to inhibit the production of all forms of TTR, and could offer an alternative approach to treat all types of transthyretin-related amyloidosis.

Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners.