CARLSBAD, Calif., June 11, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS) today provided an update on
its ongoing open-label Phase 2 clinical study of
ISIS-SMNRx in infants with Type I spinal muscular
atrophy (SMA). Previously the company reported data from this
study on event-free survival, measures of muscle function and
assessments of developmental milestones. The data reported
today show continued increases in median event-free survival and
muscle function scores as well as achievement of developmental
milestones. The safety and tolerability profile of
ISIS-SMNRx to date continues to support further
development. Isis is currently collaborating with Biogen to
develop and potentially commercialize ISIS-SMNRx to
treat patients with SMA.
The study was designed to evaluate the safety and tolerability
of ISIS-SMNRx in infants with Type I SMA and to explore
potential efficacy endpoints to support the Phase 3 program.
A total of 20 infants with SMA were dosed with either 6 mg or
12 mg of ISIS-SMNRx. SMA infants 7 months or
younger entered the study sequentially, such that the dosing of
infants in the 12 mg cohort began five to 15 months after the first
infant was dosed in the 6 mg cohort. Nineteen infants
completed the three induction doses and are evaluable for efficacy.
Clinical efficacy endpoints include event-free survival, as
defined by time to permanent ventilation or death; CHOP-INTEND
motor function scores; and assessments of developmental
milestones. An analysis as of April
17, 2015 showed that since the last analysis as of
September 2, 2014 (seven and a half
months ago):
- The median event-free age has increased for infants in both
dosing cohorts, from 16.3 months to 19.9 months for the four
infants in the 6 mg cohort, and from 11.6 months (n=12) to 16.7
months (n=15) for the infants in the12 mg cohort.
- For the seven infants in the 12 mg cohort who were in the
original group and reported on at the American Academy of Neurology
meeting in 2014, the median event-free age has increased from 9.6
months on April 7, 2014 to 21.4
months on April 17, 2015.
- Two of the four infants in the 6 mg cohort remain enrolled in
the study and are now older than 27 months of age. In the 12 mg
cohort, 11 of 15 infants (73%) are still event-free and older than
15 months of age.
- Muscle function scores have increased from baseline.
- Infants have achieved motor milestones since their baseline
evaluations.
- Only a single event has occurred: One infant in the 12 mg
cohort required permanent ventilation. There have been no deaths
since the previous analysis.
As of April 17, 2015, the median
time in study was 13.2 months. The lumbar puncture procedure in
infants with SMA has been well tolerated and shown to be feasible.
There have been no drug-related serious adverse events (SAEs)
and the majority of SAEs were related to respiratory
infections. Most of the adverse events (non-SAEs) have been
mild or moderate in severity. There were no changes in the
safety profile with repeated doses of ISIS-SMNRx.
Webcast
At 8:30 a.m. Eastern
Time, June 11, 2015, Isis will
conduct a webcast to discuss the latest ISIS-SMNRx Phase
2 study data. A live audio webcast of the presentation will
be available on the "Investors & Media" section of the
Company's website, www.isispharm.com. Interested parties may
listen to the call by dialing 877-443-5662. A replay will be
available for a limited time. The slides presented on the
webcast will be available on Isis' website at www.isispharm.com at
the time of the webcast and for a limited time after.
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-Schöneborn1, 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)2, 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
stand independently. Children with Type III have a normal
lifespan but accumulate life-long physical disabilities as they
grow.
ABOUT ISIS-SMNRx
ISIS-SMNRx 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
ISIS-SMNRx for the treatment of patients with SMA.
Isis is currently collaborating with Biogen to develop and
potentially commercialize the investigational compound,
ISIS-SMNRx, for the treatment of SMA. Under the
terms of the January 2012 agreement,
Isis 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.
Isis is conducting two Phase 3 studies of
ISIS-SMNRx. 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 ISIS-SMNRx with a primary
endpoint of event-free survival. The CHERISH study is a
randomized, double-blind, sham-procedure controlled fifteen month
study in approximately 120 non-ambulatory children with SMA.
The study will evaluate the efficacy and safety of
ISIS-SMNRx with a primary endpoint of a change in
Hammersmith Functional Motor Scale-Expanded.
For further study information, please visit
www.clinicaltrials.gov and search for ISIS-SMNRx or
visit the ISIS-SMNRx study site at www.smastudy.com.
Isis acknowledges support from the following organizations for
ISIS-SMNRx: Muscular Dystrophy Association, SMA
Foundation, Cure SMA and intellectual property licensed from Cold
Spring Harbor Laboratory and the University of
Massachusetts Medical School.
ABOUT ISIS and BIOGEN
Isis and Biogen have a broad
strategic alliance focused on leveraging antisense technology to
advance the treatment of neurological and neuromuscular disorders.
This alliance combines Isis' expertise in antisense
technology to evaluate potential neurological targets and discover
antisense drugs with Biogen's capability to develop therapies for
neurological disorders. Isis 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), ISIS-SMNRx, myotonic dystrophy
type 1 (DM1), ISIS-DMPKRx, and two undisclosed
neurodegenerative diseases, ISIS-BIIB3Rx, and
ISIS-BIIB4Rx. In addition to these four drugs,
Isis and Biogen have numerous opportunities to evaluate additional
targets for the development of drugs to treat neurological
disorders.
ABOUT ISIS PHARMACEUTICALS, INC.
Isis is exploiting
its leadership position in RNA-targeted technology to discover and
develop novel drugs for its product pipeline and for its
partners. Isis' broad pipeline consists of 38 drugs to treat
a wide variety of diseases with an emphasis on cardiovascular,
metabolic, severe and rare diseases, including neurological
disorders, and cancer. Isis' partner, Genzyme, is
commercializing Isis' lead product, KYNAMRO®, in
the United States and other
countries for the treatment of patients with homozygous FH.
Isis has numerous drugs in Phase 3 development in severe/rare
diseases and cardiovascular diseases. These include
ISIS-APOCIIIRx, a drug Isis is developing and plans to
commercialize through its wholly owned subsidiary, Akcea
Therapeutics, to treat patients with familial chylomicronemia
syndrome and familial partial lipodystrophy; ISIS-TTRRx,
a drug Isis is developing with GSK to treat patients with the
polyneuropathy and cardiomyopathy forms of TTR amyloidosis; and
ISIS-SMNRx, a drug Isis is developing with Biogen to
treat infants and children with spinal muscular atrophy, a severe
and rare neuromuscular disease. Isis' patents provide strong
and extensive protection for its drugs and technology.
Additional information about Isis is available at
www.isispharm.com.
ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This
press release includes forward-looking statements regarding Isis'
alliance with Biogen, the discovery, development, activity,
therapeutic and commercial potential and safety of
ISIS-SMNRx and the discovery, development and
therapeutic potential of an antisense drug for the treatment of
spinal muscular atrophy. Any statement describing Isis'
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. Isis' 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 Isis' forward-looking statements reflect
the good faith judgment of its management, these statements are
based only on facts and factors currently known by Isis. As a
result, you are cautioned not to rely on these forward-looking
statements. These and other risks concerning Isis' programs
are described in additional detail in Isis' 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 this press release, unless the context requires otherwise,
"Isis," "Company," "we," "our," and "us" refers to Isis
Pharmaceuticals and its subsidiaries.
Isis Pharmaceuticals® is a registered trademark of
Isis Pharmaceuticals, Inc. Akcea Therapeutics™ is a trademark
of Isis Pharmaceuticals, Inc. KYNAMRO® is a
registered trademark of Genzyme Corporation.
1 Rudnik-Schöneborn 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.
2 Finkel 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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