"In less than two years, we discovered and advanced ISIS-DMPKRx into development, and we plan to begin human clinical studies next year," said B. Lynne Parshall, chief operating officer at Isis.
DM1 is a rare genetic neuromuscular disease characterized by progressive muscle atrophy, weakness and disabling muscle spasms. DM1, the most common form of muscular dystrophy in adults, is estimated to affect approximately 150,000 patients in the U.S., Europe and Japan. DM1 is caused by a genetic defect in the dystrophia myotonica-protein kinase (DMPK) gene in which a sequence of three nucleotides repeats extensively, creating an abnormally long toxic RNA, which accumulates in the cell and prevents the production of proteins needed for normal cellular function. The severity and age of onset of DM1 correlates with the number of triplet repeats, which increases from one generation to the next. There are no disease-modifying therapies for patients with DM1 and current treatments are intended to manage symptoms and minimize disability. ISIS-DMPKRx is designed to correct the underlying genetic defect that causes DM1.
"Myotonic dystrophy represents an ideal opportunity for antisense as the disease-causing gene produces a toxic RNA that is not easily targeted with traditional therapeutic approaches," said C. Frank Bennett, Ph.D., senior vice president of research at Isis. "In our preclinical studies, we and our collaborators, Drs. Charles Thornton and Thurman Wheeler at the University of Rochester, have been able to target the toxic RNA with antisense, remove the toxic RNA and restore normal cell function.”
In June 2012, Isis entered into an alliance with Biogen Idec to discover and develop an antisense drug targeting DMPK for the treatment of DM1. Isis received an upfront payment of $12 million and is eligible to receive up to $59 million in milestone payments associated with the clinical development of ISIS-DMPKRx, including this $10 million milestone payment. Biogen Idec has the option to license ISIS-DMPKRx from Isis up through completion of the phase II study. Isis could receive up to another $200 million in a license fee and regulatory milestone payments plus double-digit royalties on sales of ISIS-DMPKSHYRx. Isis is responsible for global development of ISIS-DMPKRx through completion of phase II clinical studies, with Biogen Idec providing advice on the clinical study design and regulatory strategy. If Biogen Idec exercises its option, it will assume global development, regulatory and commercialization responsibilities.