CARLSBAD, Calif., June 22, 2015 /PRNewswire/ -- Isis
Pharmaceuticals, Inc. (NASDAQ: ISIS) today provided an update on
children with spinal muscular atrophy (SMA) who have completed the
open-label, Phase 2 multiple-dose study of ISIS-SMNRx
and are continuing to receive treatment in an open-label
extension (OLE) study. Consistent with earlier observations,
increases in muscle function scores and additional motor function
tests were observed in children treated with
ISIS-SMNRx. Isis is currently collaborating with
Biogen to develop and commercialize ISIS-SMNRx to treat
patients with SMA.
"The natural course for children with untreated type II or type
III SMA typically experience loss of muscle function that develops
slowly and continually over time, a sustained increase of three or
more points in HMFSE scores represents a significant departure from
the natural course and is unusual for these children," said Dr.
Darryl De Vivo, Professor of
Neurology and Pediatrics, Columbia
University Medical Center.
In the OLE study, a total of 30 children with Type II or Type
III SMA received 12 mg of ISIS-SMNRx dosed intrathecally
every six months. Children who enrolled in the OLE study had
completed the open-label Phase 2 study of ISIS-SMNRx in
which they had received multiple doses of either 3 mg, 6 mg, 9 mg,
or 12 mg of ISIS-SMNRx. Clinical endpoints were
measured every three months and compared to each patient's Phase 2
baseline score. These endpoints included measurements of
muscle function using the Hammersmith Functional Motor
Scale-Expanded (HFMSE), the six minute walk test (6MWT) for
ambulatory patients and the upper limb module (ULM) test for
non-ambulatory patients.
An analysis, which was performed on May
15, 2015, showed continued and durable increases in measures
of muscle function with 57% of children with SMA achieving
increases in HFSME scores of at least three points.
Analysis of muscle function measures at the nine month
evaluation in the OLE study showed:
- A mean increase of 3.8 points in HFMSE score (n=22)
- In a subgroup analysis of children who had incoming HFMSE
scores that met the inclusion criteria for the ongoing Phase 3
CHERISH study (³ 10 and ≤ 54; n=17), the mean increase
in HFMSE score was 4.4 points.
- A mean increase of 55 meters in 6MWT score (n=11).
- A mean increase of 2 points in ULM test, which measures muscle
function on an 18-point scale (n=12)
In addition, a review of the safety profile of
ISIS-SMNRx in children with SMA provided further support
for continued development.
- Intrathecal administration has been well tolerated and shown to
be feasible with no drug-related serious adverse events in either
the Phase 2 or the open-label extension studies.
- Most adverse events reported as mild or moderate in
severity.
- There were no changes in the safety profile with repeated doses
of ISIS-SMNRx.
"In these studies using multiple measurements of muscle and
motor function changes, we observed encouraging results that were
consistent with earlier results from our open-label Phase 2
study. Taken together, these data suggest that
ISIS-SMNRx could provide benefit to patients with SMA
beyond halting their disease progression," said C. Frank Bennett, Ph.D., senior vice president
of research at Isis Pharmaceuticals. "The safety and
tolerability profile that we have observed across all of our
ISIS-SMNRx studies support the ongoing Phase 3 programs
in both infants and children with SMA."
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 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. Type I is the most
severe form of SMA and most infants with Type I SMA die in infancy.
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, to treat 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.
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SOURCE Isis Pharmaceuticals, Inc.