Ionis Pharmaceuticals Completes Target Enrollment for Nusinersen Phase 3 Study, CHERISH, in Children with Spinal Muscular Atrophy

Ionis Earns $2.15M Milestone Payment from Biogen as Nusinersen Advances

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Jan 12, 2016, 07:00 ET

CARLSBAD, Calif., Jan. 12, 2016 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) announced today that it has earned a milestone payment of $2.15 million from Biogen for completing the target enrollment of the Phase 3 CHERISH study. The study is designed to support marketing approval of nusinersen in children with spinal muscular atrophy (SMA).

"Achieving our target enrollment number in CHERISH brings us one step closer to a marketing application for children with SMA. We also plan to complete enrollment in ENDEAR, our Phase 3 study evaluating nusinersen in infants with SMA, in the first half of this year. This progress sets the stage for Phase 3 data from both of these programs in 2017," said B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals. "We would like to thank the parents and families for their participation in CHERISH as well as the investigators and sites for the achievement of this milestone. We also appreciate the support from the broader SMA community. We, along with Biogen, are committed to advancing nusinersen toward the market as rapidly as possible."

CHERISH, a Phase 3 study of nusinersen, is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 117 children who are non-ambulatory with SMA between the ages of 2 to 12. The study will evaluate the efficacy and safety of 12 mg doses of nusinersen with a primary endpoint of a change in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. Additional efficacy endpoints are also included in the study. For further study information, please visit www.clinicaltrials.gov and search for nusinersen or the identifier number NCT02193074 or visit the nusinersen study site at www.smastudy.com.

ABOUT SMA
SMA is a severe genetic disease that affects approximately 30,000 to 35,000 patients in the United States, Europe and Japan. There are no approved treatments for SMA. The disease is caused by a loss of, or defect in, the survival motor neuron 1 (SMN1) gene, leading to a decrease in the survival motor neuron (SMN) protein. SMN is critical to the health and survival of nerve cells in the spinal cord that are responsible for neuromuscular growth and function. One in 50 people, the equivalent of about six million people in the United States, are carriers of a defective SMN1 gene, which is unable to produce fully functional SMN protein. Carriers experience no symptoms and do not develop the disease. However, when both parents are carriers, there is a one in four chance that their child will have SMA.

Natural history studies have been conducted in patients with SMA. Type I is the most severe form of SMA and most infants with Type I SMA die in infancy. In a 2009 paper by Rudnik-Schonebornⁱ, the median age for event-free survival in infants with Type I SMA was 6.1 months. In a contemporaneous study published in 2014 by the Pediatric Neuromuscular Clinical Research group (PNCR)ⁱⁱ, the median age for event-free survival in infants with two copies of SMN2 was 10.5 months. The severity of SMA correlates with the amount of SMN protein. Infants with Type I SMA produce very little SMN protein and have a life expectancy of less than two years. Children with Type II have greater amounts of SMN protein but still have a shortened lifespan and are never able to walk. Children with Type III have a normal lifespan but accumulate life-long physical disabilities as they grow.

ABOUT NUSINERSEN
Nusinersen, formerly referred to as ISIS-SMN_Rx, is designed to alter the splicing of SMN2, a gene that is closely related to SMN1, to increase production of fully functional SMN protein. The United States Food and Drug Administration granted orphan drug status and fast track designation to nusinersen for the treatment of patients with SMA. The European regulatory agency granted orphan drug designation to nusinersen for the treatment of patients with SMA. Ionis is currently collaborating with Biogen to develop and potentially commercialize the investigational compound, nusinersen, for the treatment of SMA. Under the terms of the January 2012 agreement, Ionis is responsible for global development and Biogen has the option to license the compound. In addition to the pivotal studies described below, Biogen is operationalizing two Phase 2 studies (NURTURE & EMBRACE) to augment the ongoing Phase 3 program.

Ionis is conducting two Phase 3 studies of nusinersen. One Phase 3 study, ENDEAR, in infants with SMA and a second Phase 3 study, CHERISH, in children with SMA. The ENDEAR study is a randomized, double-blind, sham-procedure controlled thirteen month study in approximately 110 infants diagnosed with SMA. The study will evaluate the efficacy and safety of nusinersen with a primary endpoint of event-free survival.

In addition to the Phase 3 studies, ENDEAR and CHERISH, nusinersen is being evaluated in the following four Phase 2 studies:

Biogen is evaluating nusinersen in an open-label study, NURTURE, in approximately 25 pre-symptomatic newborns who are genetically diagnosed with SMA but presymptomatic.
Biogen is evaluating nusinersen in a randomized, double-blind, sham-procedure controlled study, EMBRACE, in 21 patients who do not meet the age and inclusion criteria of ENDEAR and CHERISH studies.
Ionis is evaluating nusinersen in a Phase 2 open-label study in 20 infants with SMA. Infants in this study have been on treatment for up to 29 months. In June 2015, Ionis reported that it had observed increases in median event-free survival and increases in muscle function scores as well as the achievement of developmental milestones in infants who received nusinersen in its open-label Phase 2 study.
Ionis is evaluating nusinersen in a Phase 2 open-label extension study in 30 children who have completed dosing in one of the earlier nusinersen studies. Patients in this study have been on treatment for up to 46 months. In June 2015, Ionis reported that it had observed increases in muscle function scores and additional motor function tests in children who received nusinersen.

Ionis has also completed dosing in three additional nusinersen studies that evaluated a single or multiple dose of nusinersen in 56 children with Type II and Type III SMA. Children who completed these studies were eligible to roll over into the Phase 2 open-label extension study.

For further study information, please visit www.clinicaltrials.gov and search for nusinersen or visit the nusinersen study site at www.smastudy.com.

Ionis acknowledges support from the following organizations for nusinersen: Muscular Dystrophy Association, SMA Foundation, Cure SMA and intellectual property licensed from Cold Spring Harbor Laboratory and the University of Massachusetts Medical School.

ABOUT IONIS and BIOGEN
Ionis and Biogen have a broad strategic alliance focused on leveraging antisense technology to advance the treatment of neurological and neuromuscular disorders. This alliance combines Ionis' expertise in antisense technology to evaluate potential neurological targets and discover antisense drugs with Biogen's capability to develop therapies for neurological disorders. Ionis is primarily responsible for drug discovery and early development of antisense therapies. Biogen has the option to license each antisense program at a particular stage in development. Current development-stage programs include antisense drugs to treat patients with spinal muscular atrophy (SMA), nusinersen; myotonic dystrophy type 1 (DM1), IONIS-DMPK-2.5_Rx; amyotrophic lateral sclerosis (ALS), IONIS-SOD1_Rx; and an undisclosed neurodegenerative disease, IONIS-BIIB4_Rx. In addition to these four drugs, Ionis and Biogen have numerous opportunities to evaluate additional targets for the development of drugs to treat neurological disorders.

ABOUT IONIS PHARMACEUTICALS, INC.
Ionis Pharmaceuticals 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 a dozen drugs in mid- to late-stage development. Drugs currently in Phase 3 development include volanesorsen, a drug Ionis is developing and plans to commercialize through its wholly owned subsidiary, Akcea Therapeutics, to treat patients with familial chylomicronemia syndrome and familial partial lipodystrophy; IONIS-TTR_Rx, a drug Ionis is developing with GSK to treat patients with all forms of TTR amyloidosis; and nusinersen, a drug Ionis is developing with Biogen to treat infants and children with spinal muscular atrophy. Ionis' patents provide strong and extensive protection for its drugs and technology. Additional information about Ionis is available at www.ionispharma.com.

IONIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This press release includes forward-looking statements regarding Ionis' strategic relationship with Biogen, the discovery, development, activity, therapeutic and commercial potential and safety of nusinersen for the treatment of spinal muscular atrophy and the discovery, development, activity, therapeutic potential, safety and commercialization of drugs under Ionis' relationship with Biogen. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2014, and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

In December, 2015, the Company changed its name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.

In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark of Ionis Pharmaceuticals, Inc.

ⁱRudnik-Schoneborn S, Berg C, Zerres K, et al. Genotype-phenotype studies in infantile spinal muscular atrophy (SMA) type 1 in Germany: implications for clinical trials and genetic counselling. Clin Genet. 2009;76(2):168-78.

ⁱⁱFinkel RS et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014 Aug 26;83(9):810-7.

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