Under the agreement, Isis will receive a $29 million upfrontpayment, with the potential to receive up to $45 million in milestone paymentsassociated with clinical development of the drug prior to licensing, and Isiswill be responsible for global development through the completion of PhaseII/III registration trials. For its part, Biogen Idec will have the option tolicense ISIS-SMNRx until the completion of the first successful Phase II/IIItrial, and will provide advice on clinical trial design and regulatorystrategy. If the option is exercised, Biogen Idec will be responsible forglobal development, regulation and commercialization, and Isis will be eligiblefor up to $225 million in a license fee and regulatory milestone payments.
"[SMA] is exactly the kind of disease and program that weare focused on at Biogen Idec," Dr. George A. Scangos, CEO of Biogen Idec, saidin a press release. "The unmet need could not be any greater, the program fitswith our mission to bring innovative therapies to patients with seriousneurologic diseases and Isis' antisense compound has the potential to be ahighly effective, first-to-market therapy for this deadly disease. We have theutmost respect for Isis' scientific leadership and expertise in antisensetechnology, and we have crafted a collaboration that brings together our twocompanies' strengths toward a common goal."
SMA affects approximately 30,000 to 35,000 people in theUnited States, Europe and Japan, and is caused by a genetic defect related tothe survival motor neuron 1 gene. The survival motor neuron (SMN) protein is arequirement for normal muscle development and function, but in SMA sufferers,the SMN protein is either not produced or only a truncated form is produced.The lack of the SMN protein leads to death in the worst form, Type I, andlifelong physical disabilities, a shortened lifespan and an inability to moveindependently in Types II and III.
ISIS-SMNRx is an antisense therapy that affects how a cellreads RNA, altering the splicing so that a normal SMN protein is produced. Thedrug has received both orphan drug status and fast-track designation from theU.S. Food and Drug Administration, and has been supported by the SMAFoundation, the Muscular Dystrophy Association, Families of SMA andintellectual property licensed from Cold Spring Harbor Laboratory and theUniversity of Massachusetts Medical School. B. Lynne Parshall, director, chiefoperating officer and chief financial officer for Isis, notes that ISIS-SMNRxwas first put into Isis' pipeline in 2009, but is based on research the companyhas done on splicing previously.
"We have an accelerated development plan planned, so we'llbe doing a Phase I program that's a pretty typical Phase I program in childrenwith SMA," says Parshall of the development plans for ISIS-SMNRx. "And then weplan to go directly into two parallel Phase II/III studies, one in the verysevere Type I patients, who are the patients who frequently die in infancy, andthe second in the less severe Type II/III patients, who are the children whomanage to live with the disease but who are seriously disabled."
Naomi Aoki, director of public affairs and spokeswoman forBiogen Idec, says ISIS-SMNRx appealed to them both in the fact that Biogen Idecwas impressed with the science and preclinical data and because the program"fit with our strategic focus not only in neurology, but really looking atprograms where we think we have the greatest potential to really make a differencein patients' lives."
"It's a particularly terrible disease. In its worst form, itkills children by the time that they're two. And again, in that really severeform of the disease, children are never even able to sit up independently, andthere are no approved therapies for it right now," says Aoki, adding thatBiogen Idec thinks the therapy represents "a substantial opportunity."
"Biogen Idec's expertise in the global development andcommercialization of innovative new therapies for neurologic diseases is agreat strategic fit to advance ISIS-SMNRx … We believe that, together withBiogen Idec, we will be able to expeditiously develop this investigational drugin hopes of bringing to market an effective and desperately needed treatment toimprove the lives of children with SMA," Dr. Stanley T. Crooke, chairman of theboard and CEO of Isis, said in a press release.