Summit Therapeutics plc (NASDAQ:SMMT) (AIM:SUMM), the drug
discovery and development company advancing therapies for rare
diseases and infectious diseases, today announces positive 24-week
interim results from the open-label Phase 2 proof of concept
clinical trial, PhaseOut DMD. PhaseOut DMD is evaluating the
utrophin modulator ezutromid in patients with Duchenne muscular
dystrophy (‘DMD’). The focus of the planned interim analysis was on
biopsy measures that show:
- Treatment with ezutromid resulted in a statistically
significant and meaningful reduction in muscle damage as measured
by a 23% decrease in mean developmental myosin in muscle biopsies
at 24 weeks compared to baseline (11.37% to 8.76%, 95% CI, -4.33,
-0.90). Developmental myosin is a biomarker of muscle damage and is
found in repairing fibres.
- A total of 14 of 22 patients showed a decrease in developmental
myosin, with five of those showing a greater than 40%
reduction.
- Increase in mean utrophin protein intensity levels of 7% in
biopsies at 24 weeks compared to baseline (0.370 to 0.396, 95% CI,
-0.005, 0.058).
The combination of reduced muscle fibre damage
and increased levels of utrophin provides the first evidence of
ezutromid target engagement and proof of mechanism.
“The significant reduction in muscle damage
coupled with the increase in utrophin expression seen in PhaseOut
DMD trial patients at 24 weeks is very encouraging as it suggests
ezutromid may slow the relentless cycle of muscle fibre
degeneration and regeneration that is a hallmark of DMD,”
said Professor Francesco Muntoni, Director
of the Dubowitz Neuromuscular Centre, at the UCL Institute of Child
Health and Great Ormond Street Hospital for Children, London,
UK, and Principal Investigator in PhaseOut
DMD. “These favourable interim results are certainly a
step forward in the development of utrophin modulation as a
treatment approach for this fatal disease in all patients with
DMD.”
“The benefits of continual production of
utrophin protein to protect against the progression of DMD have
been well established in preclinical studies,” added
Professor Dame Kay E. Davies FRS, Dr Lee’s Professor of Anatomy of
the University of Oxford and Co-Founder of Summit. “These
data provide the first evidence of utrophin modulation working in
patients. If further findings build on this evidence they could
establish ezutromid as a universal, disease-modifying treatment and
bring hope to all patients and families living with DMD.”
DMD is caused by genetic faults that prevent
muscle cells from making dystrophin, a protein that maintains the
structure and healthy functioning of muscles. The absence of
dystrophin, as seen in patients with DMD, leads to a catastrophic
cycle of muscle damage and repair. Utrophin protein performs a
similar role to dystrophin in developing and repairing muscle
fibres. As a muscle fibre matures, utrophin is switched off and
replaced by dystrophin in the case of healthy individuals. During
the early stages of natural muscle repair, utrophin and
developmental myosin are expressed concurrently, and are then
slowly switched off. Ezutromid aims to maintain utrophin expression
in patients with DMD so it can substitute for the lack of
dystrophin and break this cycle.
“Achieving this significant reduction in muscle
damage after only 24 weeks of ezutromid treatment is a landmark
moment for our utrophin modulation programme,” commented Mr
Glyn Edwards, Chief Executive Officer of Summit. “These
promising interim data enhance our belief that longer-term
treatment with ezutromid could achieve meaningful functional
benefits for patients living with DMD. We now look forward to
announcing the top-line data from the full 48-week trial in the
third quarter of this year and in parallel accelerating
preparations for the advancement of ezutromid into a pivotal
clinical trial in patients.”
Additional findings from the PhaseOut DMD
24-week interim results:
- All patients achieved plasma levels of ezutromid sufficient to
modulate utrophin.
- Pharmacological responses were observed in patients treated
with either the F3 or F6 formulations. There were no observed
relationships between drug exposure and responses in pharmacology
or safety measures at this stage.
- In an additional biopsy measure, average muscle fibre diameter
decreased from 42.1µm at baseline to 40.3µm at 24-weeks.
- Changes in muscle pathology can be monitored using magnetic
resonance spectroscopy (‘MRS’) to evaluate the amount of fat in
muscles, which increases over time in DMD. The mean fat fraction in
the vastus lateralis (thigh) was 14.7% at baseline and 18.5% at 24
weeks (n=37). Longer term dosing of patients is expected to be
required to detect changes in MRS parameters, which is the 48-week
primary endpoint.
- Functional tests, which naturally decline over time in DMD,
were included as exploratory measures. The mean six-minute walk
distance was 404m at baseline and 395m at 24 weeks (n=39). Mean
North Star Ambulatory Assessment score was 25.0 at baseline and
24.4 at 24 weeks (n=39). The North Star Ambulatory Assessment is a
multi-point test of motor function with a maximum score of 34.
- All patients retained ambulation after 24 weeks of
treatment.
- Ezutromid has been well tolerated to date.
The muscle biopsies were analysed using fully
automated techniques that can assess whole cross-sections of
biopsies containing several thousand individual fibres. These
techniques were developed by Summit in collaboration with Flagship
Biosciences Inc. Following strict handling and processing
protocols, all biopsies contributed to the overall dataset with 22
matched pairs of baseline/week 24 biopsies assessed in the
developmental myosin and fibre diameter assay and 18 matched pairs
of baseline/week 24 biopsies assessed in the utrophin assay.
PhaseOut DMD is ongoing. Top-line results are
expected to be reported in the third quarter of 2018. After 48
weeks of treatment, all patients have the option of enrolling into
an extension phase, which is gathering long-term MRS, functional
and safety data on ezutromid; to date 18 of 19 eligible patients
have enrolled into the extension phase. Summit plans to conduct a
randomised, placebo controlled trial that could potentially support
the accelerated and conditional approval of ezutromid in the US and
EU respectively.
Additional details of the 24-week interim data
are expected to be presented at medical and scientific
conferences.
About PhaseOut DMDPhaseOut DMD
aims to provide proof of concept for ezutromid and utrophin
modulation by measuring utrophin protein and muscle fibre
regeneration in muscle biopsies, as well as muscle fat
infiltration. The primary endpoint of the open-label trial is the
change from baseline in magnetic resonance spectroscopy parameters
related to fat infiltration and inflammation of the leg muscles.
Biopsy measures evaluating utrophin and muscle damage are included
as secondary endpoints. Exploratory endpoints include the
six-minute walk distance, the North Star Ambulatory Assessment and
patient reported outcomes. PhaseOut DMD enrolled 40 patients in the
US and UK, aged from their fifth to their tenth birthdays. PhaseOut
DMD is 48 weeks in length. Under the protocol, 30 patients receive
2,500mg of the F3 formulation of ezutromid twice a day and ten
patients receive 1,000mg of the F6 formulation of ezutromid twice a
day. All patients had a bicep muscle biopsy taken at baseline with
24 patients scheduled to have their second biopsy after 24 weeks of
dosing, and the remaining 16 patients scheduled to have their
second biopsy after 48 weeks of dosing. The number of patients on
each formulation assigned to each biopsy group is proportionally
consistent. Two patients withdrew from the trial prior to their
second biopsy for reasons unrelated to ezutromid; one patient was
on a 24-week second biopsy schedule and the other was on a 48-week
second biopsy schedule.
Conference Call DetailsSummit
will host a conference call and webcast to review the data today at
1:00pm GMT / 8:00am EST. To participate in the conference call,
please dial +44 (0)330 336 9411 (UK and international participants)
or +1 323-794-2551 (US local number) and use the conference
confirmation code 2238624. Investors may also access a live audio
webcast of the call via the investors section of the Company’s
website www.summitplc.com. A replay of the webcast will be
available shortly after the completion of the call.
About Utrophin Modulation in
DMD DMD is a progressive muscle wasting disease that
affects around 50,000 boys and young men in the developed world.
The disease is caused by different genetic faults in the gene that
encodes dystrophin, a protein that is essential for the healthy
function of all muscles. There is currently no cure for DMD and
life expectancy is into the late twenties. Utrophin protein is
functionally and structurally similar to dystrophin. In preclinical
studies, the continued expression of utrophin had meaningful,
positive effect on muscle performance. Summit believes that
utrophin modulation has the potential to slow down or even stop the
progression of DMD, regardless of the underlying dystrophin gene
mutation. Summit also believes that utrophin modulation could
potentially be complementary to other therapeutic approaches for
DMD. The Company’s lead utrophin modulator, ezutromid, is an orally
administered, small molecule. DMD is an orphan disease, and the US
Food and Drug Administration (‘FDA’) and the European Medicines
Agency have granted orphan drug status to ezutromid. Orphan drugs
receive a number of benefits including additional regulatory
support and a period of market exclusivity following approval. In
addition, ezutromid has been granted Fast Track designation and
Rare Pediatric Disease designation by the FDA.
About Summit Therapeutics
Summit is a biopharmaceutical company focused on the discovery,
development and commercialisation of novel medicines for
indications for which there are no existing or only inadequate
therapies. Summit is conducting clinical programs focused on the
genetic disease Duchenne muscular dystrophy and the infectious
disease C. difficile infection. Further information is available at
www.summitplc.com and Summit can be followed on Twitter
(@summitplc).
For more information, please contact:
Summit |
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Glyn
Edwards / Richard Pye (UK office) |
Tel: |
44
(0)1235 443 951 |
Erik
Ostrowski / Michelle Avery (US office) |
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+1
617 225 4455 |
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Cairn Financial Advisers LLP (Nominated
Adviser) |
Tel: |
+44
(0)20 7213 0880 |
Liam
Murray / Tony Rawlinson |
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N+1 Singer (Joint Broker) |
Tel: |
+44
(0)20 7496 3000 |
Aubrey Powell / Jen Boorer |
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Panmure Gordon (Joint Broker) |
Tel: |
+44
(0)20 7886 2500 |
Freddy Crossley, Corporate Finance |
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Tom
Salvesen, Corporate Broking |
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MacDougall Biomedical Communications (US) |
Tel: |
+1
781 235 3060 |
Karen
Sharma |
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ksharma@macbiocom.com |
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Consilium Strategic Communications (UK) |
Tel: |
+44
(0)20 3709 5700 |
Mary-Jane Elliott / Jessica Hodgson / |
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summit@consilium-comms.com |
Philippa Gardner/ Rosie Phillips |
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Forward-looking StatementsAny
statements in this press release about Summit’s future
expectations, plans and prospects, including but not limited to,
statements about the clinical and preclinical development of
Summit’s product candidates, the therapeutic potential of Summit’s
product candidates, the timing of initiation, completion and
availability of data from clinical trials, the potential submission
of applications for regulatory approvals, the sufficiency of
Summit’s cash resources, and other statements containing the words
“anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,”
“intend,” “may,” “plan,” “potential,” “predict,” “project,”
“should,” “target,” “would,” and similar expressions, constitute
forward-looking statements within the meaning of The Private
Securities Litigation Reform Act of 1995. Actual results may differ
materially from those indicated by such forward-looking statements
as a result of various important factors, including: the
uncertainties inherent in the initiation of future clinical trials,
availability and timing of data from ongoing and future clinical
trials and the results of such trials, whether preliminary results
from a clinical trial will be predictive of the final results of
that trial or whether results of early clinical trials or
preclinical studies will be indicative of the results of later
clinical trials, expectations for regulatory approvals,
availability of funding sufficient for Summit’s foreseeable and
unforeseeable operating expenses and capital expenditure
requirements and other factors discussed in the “Risk Factors”
section of filings that Summit makes with the Securities and
Exchange Commission including Summit’s Annual Report on Form 20-F
for the fiscal year ended January 31, 2017. Accordingly,
readers should not place undue reliance on forward looking
statements or information. In addition, any forward-looking
statements included in this press release represent Summit’s views
only as of the date of this release and should not be relied upon
as representing Summit’s views as of any subsequent date. Summit
specifically disclaims any obligation to update any forward-looking
statements included in this press release.
This announcement contains inside information
for the purposes of Article 7 of EU Regulation 596/2014 (MAR).
-END-
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