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HUNTINGTON'S DISEASE: Enrollment in Phase 1/2a Study of IONIS-HTT Rx in Patients with HD Completed and Open-Label Extension Study to Open in 2H 2017; Anti-Sense Drug Designed to Reduce Production of All Forms of HTT, Including Mutant HTT

On June 22, 2017, Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) announced completion of enrollment in the Phase 1/2a randomized, placebo-controlled, dose escalation study of IONIS-HTTRx in patients with Huntington's disease (HD). Dosing in the final patient cohort continues, and Ionis plans to report top-line results from this study around year-end 2017. The safety and tolerability profile of IONIS-HTTRx in the completed cohorts of the Phase 1/2a study supports its continued development. Patients who complete the Phase 1/2a study will be eligible to participate in an open-label extension (OLE) study that Ionis plans to initiate in the next several months. Roche, Ionis' partner for this drug, continues to advance and support the program. IONIS-HTTRx is the first therapy in clinical development targeting the cause of HD by reducing the production of the toxic mutant huntingtin protein (mHTT) from the mutated huntingtin gene. "We are encouraged by the safety profile of IONIS-HTTRx we have observed to date in the completed dosing cohorts in the Phase 1/2a study. Upon completion and full analysis of this study, the next step for this program will be to conduct a study to investigate whether decreasing mutant huntingtin protein with IONIS-HTTRx can slow the progression of this terrible disease," said C. Frank Bennett, PhD, Senior Vice President of Research at Ionis Pharmaceuticals. "We believe that IONIS-HTTRx, which is designed to reduce the production of all forms of the huntingtin (HTT) protein – the known cause of HD, represents the most promising opportunity to address this significant unmet medical need. Together with our partners at Roche, we are committed to developing IONIS-HTTRx, which has the potential to transform the treatment of HD." IONIS-HTTRx is an antisense drug in development for the treatment of HD. IONIS-HTTRx is designed to reduce the production of all forms of the huntingtin (HTT) protein, which in its mutated variant (mHTT) is responsible for HD. As such, IONIS-HTTRx offers a unique approach to treat all patients with HD, irrespective of their individual HTT mutation. IONIS-HTTRx has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of patients with HD. HD is a rare genetic, progressive, neurodegenerative disease resulting in deterioration in mental abilities and physical control. In the U.S., there are approximately 30,000 symptomatic patients and more than 200,000 people at-risk of inheriting HD. HD is referred to as a triplet repeat disorder and is one of a large family of genetic diseases in which certain gene sequences are mistakenly repeated. In HD, the gene that encodes the HTT protein contains a trinucleotide sequence that is repeated in the gene more than 36 times. The resulting mHTT protein is toxic and gradually damages neurons in the brain. Symptoms of HD usually appear between the ages of 30 to 50 years, and continually worsen over a 10- to 25-year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure, or other complications. Presently, there is no effective disease-modifying treatment for HD available, and current approaches only focus on managing some of the disease symptoms.


Roche and Ionis are collaborating to develop antisense drugs to treat HD. The alliance combines Ionis' antisense expertise with Roche's knowledge in clinical development of anti-neurodegenerative therapeutics. To date, Ionis has earned $55 million in upfront and milestone payments from its relationship with Roche and is eligible to earn additional milestone payments as the drug progresses in development, as well as royalties on sales of IONIS-HTTRx if it is commercialized. Roche has the option to license IONIS-HTTRx from Ionis through the completion of the Phase 1/2a study. Prior to option exercise, Ionis is responsible for the discovery and development of IONIS-HTTRx. If Roche exercises its option, it will assume responsibility for global clinical development, regulatory, and commercialization activities for the drug.

CHDI Foundation, Inc. ( provided financial and scientific support to Ionis' HD drug discovery program through a development collaboration with Ionis. Over time, CHDI will be reimbursed for its support of Ionis' program out of milestone payments received by Ionis.


Ionis is the leading company in RNA-targeted drug discovery and development focused on developing drugs for patients who have the highest unmet medical needs, such as those patients with severe and rare diseases. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over three dozen drugs in development. SPINRAZA® (nusinersen) is a drug that has been approved in the U.S. and Europe for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients. Biogen is responsible for commercialization of SPINRAZA. Drugs that have successfully completed Phase 3 studies include volanesorsen, a drug Ionis is developing and plans to commercialize through its subsidiary, Akcea Therapeutics, to treat patients with either familial chylomicronemia syndrome or familial partial lipodystrophy; and inotersen (IONIS-TTRRx), a drug Ionis is developing with GSK to treat patients with TTR amyloidosis. Both drugs are progressing toward regulatory filings in the second half of 2017. Ionis' patents provide strong and extensive protection for its drugs and technology. Additional information about Ionis is available at

[Press release] [Ionis Pharma]