SOUTH PLAINFIELD, N.J.,
Oct. 3, 2018 /PRNewswire/
-- PTC Therapeutics, Inc. (NASDAQ: PTCT) today
announced interim clinical data from the Part 1, open-label studies
of FIREFISH and SUNFISH demonstrating the benefit of risdiplam
(RG7916) for the treatment of Type 1, 2 and 3 spinal muscular
atrophy (SMA). The results showed that patients across all SMA
types benefited from an oral systemic therapy indicated by
increases in developmental motor milestones. Risdiplam was well
tolerated at all doses across studies to date and no participants
have withdrawn due to drug-related safety findings. The pivotal
portions of both studies are ongoing. The data were presented at
the 23rd International Annual Congress of the World Muscle Society
in Argentina. The SMA program is a
collaboration between PTC, the SMA Foundation, and Roche.
"The emerging results from FIREFISH and SUNFISH trials support
the broad clinical benefit of a systemic oral treatment for SMA
patients," said Stuart W. Peltz,
Ph.D., Chief Executive Officer of PTC Therapeutics. "Patients with
Type 2 and 3 SMA typically decline over the course of a year and
the increase in motor function by over 3 points in SUNFISH when
compared to natural history is exceptionally encouraging. We are
excited by the gains in developmental motor milestones exhibited by
Type 1 babies in FIREFISH. The observation of six babies sitting to
date in a dose finding study is remarkable. SMA is a systemic
disease, and risdiplam which is an oral treatment that reaches all
affected organs has the potential to be a best-in-class
therapy."
In Part 1 of the FIREFISH study, at Day 245 of treatment, 43%
(6/14) of infants were able to sit (with or without support),
including three who achieved unassisted sitting. Natural history
indicates that Type 1 SMA babies never achieve this milestone.
Ninety percent of babies remain alive with two having discontinued
due to the fatal progression of their disease. In Part 1 of the
SUNFISH study in Type 2 and 3 SMA patients, 63% (19/30) of patients
treated with risdiplam for at least one year achieved a median
increase in motor function (as measured by MFM32) of 3.13 points
versus baseline. Typically patients with Type 2 or 3 SMA decline by
0.85 to 0.67 point per year1. In addition, median SMN
protein level increases of greater than 2-fold were sustained over
12 months.
The pivotal portion of the SUNFISH clinical study has completed
enrollment. Part 2 of SUNFISH is a randomized, double-blinded,
multi-center, placebo-controlled study which enrolled 180 Type 2
and Type 3 SMA patients 2-25 years of age for 24 months, followed
by an open-label extension. Patients enrolled in the SUNFISH trial
have a broad age range (2-24 years; median age 8 years) and with
broad functional characteristics. The primary endpoint is change
from baseline in the total Motor Function Measure 32 (MFM-32) score
at Month 12.
Risdiplam is an investigational small molecule SMN2 splicing
modifier targeting the survival motor neuron 2 (SMN2) RNA,
restoring a functional transcript. In preclinical studies,
risdiplam, which was given orally, crossed the blood brain barrier,
and showed systemic distribution to the organs that are affected by
low levels of SMN protein.
The table below
depicts improvements across the FIREFISH and SUNFISH dose-finding
studies:
|
FIREFISH
|
Outcome
|
Result
|
Sitting after 8
months of treatment
(n=14)
|
- 6 infants (43%) sit
with or without support including 3 infants (21%) who
sit without assistance
|
Motor milestone
achievement after 8
months of treatment
(n=14)
|
- 10 infants (71%)
achieved full or partial head control including 6 (43%)
babies with upright head control
- 7 infants (50%)
kicking
- 4 infants (29%)
demonstrated rolling to the side
|
Survival
|
- 90% (19/21) babies
were event-free vs. 50% of age-matched SMA Type 1
babies in natural history studies
|
Pulmonary
function
and swallowing
|
- No baby has
required tracheostomy, reached permanent ventilation or
lost the ability to swallow (Latest visit day - 546
days)
|
CHOP-INTEND
|
- Increases over time
– from 5.5 points median at Day 56 (n=20) to 16
points median at Day 245 (n=14)
- Increases in
younger and older patients – 18.5 points median for babies
3-5 months old (n=4) and 14.5 points median for babies 5-7 months
old
(n=10) at Day 245
- 13 infants (93%)
achieved ≥4-point increase (n=14) at Day 245
- 8 infants (57%)
achieved a score of 40 or above (n=14) at Day 245
|
The most common adverse events were fever (pyrexia: 52.4%,)
diarrhea (26.8%), upper respiratory tract infections (19%), ear
infections (14.3%), pneumonia (14.3%), constipation (14.3%),
vomiting (14.3%), cough (14.3%) and upper respiratory inflammation
(14.3%). Data cutoff: 7-Sept
2018.
SUNFISH
|
Endpoint:
(at 12 months of
treatment)
|
>12 months
Treatment
|
MFM
|
All
patients
(n=30) *
|
Aged 2-11
(n=17)
|
Aged 12-24
(n=13)
|
Total MFM change from
baseline,
mean (SD)
|
2.47
(4.17)
|
3.31 (4.5)
|
1.36
(3.57)
|
Total MFM change from
baseline,
median (range)
|
3.13
(-7.3-11.5)
|
4.17
(-6.3-11.5)
|
2.08
(-7.3-5.2)
|
Proportion of
patients who achieve
improvement (i.e. a change from
baseline in MFM score ≥3), % (n)
|
63.3
(19/30)
|
76.5
(13/17)
|
46.2
(6/13)
|
*Excludes 4 patients
who performed the MFM20 assessment (only patients who performed the
full MFM32 assessment are included in the analysis) and one patient
who had dropped out of the study prior to the Month 12 visit.
Serious adverse events that occurred in two or more of the 51
patients were nausea (4%), upper respiratory tract infection (4%),
and vomiting (4%). Data cut-off 6th July
2018.
|
For more information on the Congress, visit
http://www.wms2018.com/
About Spinal Muscular Atrophy (SMA)
Spinal muscular
atrophy (SMA) is a genetic neuromuscular disorder that is the
leading genetic cause of mortality in infants and toddlers caused
by a missing or defective survival of motor neuron 1 (SMN1) gene,
which results in reduced levels of SMN protein. The homologous SMN2
pre-mRNA is predominantly spliced to a truncated mRNA, and only
produces small amounts of functional SMN protein. Insufficient
levels of SMN protein are responsible for the loss of motor neurons
within the spinal cord leading to muscle atrophy and death in its
most severe form. It is estimated that this devastating disease
affects 1 in every 11,000 children born.
About the SMA Clinical Trials
FIREFISH: An
open-label, two-part clinical trial. Part 1 was a dose escalation
study in 21 infants. The primary objective of Part 1 was to assess
the safety profile of risdiplam in infants and determine the dose
for Part 2. Part 2 is a single-arm study with the dose selected in
Part 1 in approximately 40 infants with Type 1 SMA for 24 months,
followed by an open-label extension. This study is recruiting
globally.
SUNFISH: A double‐blind, two‐part, placebo‐controlled
trial. Part 1 enrolled patients with Type 2 or 3 SMA to evaluate
the safety, tolerability, and PK/PD of several risdiplam dose
levels. The pivotal SUNFISH Part 2, in non‐ambulant patients with
Type 2 or 3 SMA, is evaluating safety and efficacy of the risdiplam
dose level selected from Part 1 for 24 months, followed by an open
label extension. This study has finished recruiting globally.
JEWELFISH: An ongoing, exploratory, open-label study to
establish the safety and tolerability of risdiplam in people with
SMA who have previously participated in a study with another
therapy targeting SMN2 splicing.
About the SMA collaboration
The SMA program was
initiated by PTC Therapeutics in partnership with the SMA
Foundation in 2006. In November 2011,
Roche gained an exclusive worldwide license to the PTC/SMA
Foundation SMN2 alternative splicing program. The development of
risdiplam RG7916 is being executed globally by Roche, including in
the US through Genentech, a member of the Roche group. The SMA
program is overseen by a Joint Steering Committee with members from
PTC, Roche, and the SMA Foundation.
About PTC Therapeutics, Inc.
PTC is a science-led,
global biopharmaceutical company focused on the discovery,
development and commercialization of clinically-differentiated
medicines that provide benefits to patients with rare disorders.
Founded 20 years ago, PTC Therapeutics has successfully launched
two rare disorder products and has a global commercial footprint.
This success is the foundation that drives investment in a robust
pipeline of transformative medicines and our mission to provide
access to best-in-class treatments for patients who have an unmet
medical need.
For More Information:
Investors:
Emily
Hill
+1 (908) 912-9327
ehill@ptcbio.com
Media:
Jane Baj
+1 (908) 912-9167
jbaj@ptcbio.com
Forward-Looking Statements:
All statements,
other than those of historical fact, contained in this press
release, are forward-looking statements, including statements
regarding: any advancement of the joint development program in SMA
with PTC, Roche, and SMAF, in particular as related to the timing
of enrollment, completion and evaluation of the Phase 2 clinical
studies of risdiplam in SMA patients and the period during which
the results of the studies will become available; the clinical
utility and potential advantages of risdiplam, including its
potential to impact every aspect of the disease; the timing and
outcome of PTC's regulatory strategy and process; PTC's strategy,
future expectations, plans and prospects, future operations, future
financial position, future revenues or projected costs; and the
objectives of management. Other forward-looking statements may be
identified by the words "potential," "will," "promise," "expect,"
"plan," "target," "anticipate," "believe," "estimate," "intend,"
"may," "project," "possible," "would," "could," "should,"
"continue," and similar expressions.
PTC's actual results, performance or achievements could differ
materially from those expressed or implied by forward-looking
statements it makes as a result of a variety of risks and
uncertainties, including those related to: the initiation,
enrollment, conduct and availability of data from either the
SUNFISH or FIREFISH studies and the outcome of such studies; events
during, or as a result of, these studies that could delay or
prevent further development of risdiplam, including future actions
or activities under the SMA joint development program; our
expectations for regulatory approvals; PTC's scientific approach
and general development progress; and the factors discussed in the
"Risk Factors" sections of PTC's most recent Quarterly Report on
Form 10-Q and Annual Report on Form 10-K as well as any updates to
these risk factors filed from time to time in PTC's other filings
with the SEC. You are urged to carefully consider all such
factors.
As with any pharmaceutical under development, there are
significant risks in the development, regulatory approval and
commercialization of new products, including with respect to PTC's
joint development program in SMA with Roche and the SMAF. There are
no guarantees that any product candidate under the joint
development program will receive regulatory approval in any
territory or prove to be commercially successful.
The forward-looking statements contained herein represent PTC's
views only as of the date of this press release and PTC does not
undertake or plan to update or revise any such forward-looking
statements to reflect actual results or changes in plans,
prospects, assumptions, estimates or projections, or other
circumstances occurring after the date of this press release except
as required by law.
1 Vuillerot, C., et al. Responsiveness of the Motor
Function Measure in Patients with Spinal Muscular Atrophy. Archives
of Physical Medicine and Rehabilitation. 2013; 94: 1555-61.
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