Summit Announces New Analysis Showing Ezutromid Significantly Reduced Muscle Inflammation in Phase 2 Clinical Trial in DMD
26 February 2018 - 11:00PM
Summit Therapeutics plc (NASDAQ:SMMT) (AIM:SUMM) announces further
positive findings from PhaseOut DMD, a Phase 2 open-label,
multi-centre clinical trial of the utrophin modulator ezutromid in
Duchenne muscular dystrophy (‘DMD’). Further analysis of the
24-week interim dataset showed a statistically significant decrease
in muscle inflammation as measured by magnetic resonance
spectroscopy transverse relaxation time T2 (‘MRS-T2’).
“MRS-T2 is an objective technique used to
monitor DMD disease progression as it allows for the precise
quantification of changes in muscle breakdown and inflammation.
MRS-T2 values typically increase over time in DMD,”
commented Dr H Lee Sweeney, Director of the Myology
Institute at the University of Florida and Co-Director of Imaging
DMD. “The decrease in MRS-T2 seen in PhaseOut DMD is
encouraging and suggests ezutromid is having a positive effect on
muscle health. These data could be an early indication that these
patients are experiencing a decrease in disease severity and
highlight ezutromid’s potential as a disease modifying treatment. I
look forward to seeing further findings from PhaseOut DMD.”
The reduction in MRS-T2 measured in PhaseOut DMD
is consistent with the expected activity of ezutromid to stabilise
muscle fibre membranes and thereby reduce muscle fibre damage and
inflammation. A statistically significant and meaningful reduction
in muscle fibre damage was observed in previously reported 24-week
findings from patient biopsies in PhaseOut DMD.
Published research has shown reductions in
MRS-T2 in DMD patients treated with steroids.[1] All patients in
PhaseOut DMD have been on stable steroid regimens and therefore the
MRS-T2 reductions observed are in addition to any anti-inflammatory
effect provided by steroids.
The new MRS data showed a statistically
significant decrease from baseline in the T2-relaxation time in the
soleus (calf muscle) in patients (n=38) treated with ezutromid. The
mean decrease was -0.861 milliseconds from baseline to 24 weeks
(31.850 milliseconds to 30.989 milliseconds, 95% CI, -1.440,
-0.281). The soleus is one of the most reliable leg muscles for
monitoring disease progression via T2 relaxation time in DMD with
increases shown to correlate to loss of functional ability.[1,2]
Published natural history data show that T2 relaxation times
increase with disease progression due to the relentless cycle of
muscle damage and repair leading to inflammation.[1,2] A mean
decrease of -0.470 milliseconds in MRS-T2 was also observed in the
vastus lateralis (thigh muscle) in ezutromid-treated patients
(n=37) from baseline to 24 weeks (32.265 milliseconds to 31.795
milliseconds, 95% CI, -1.158, 0.218).
“The 24-week interim analysis has shown
encouraging signs of ezutromid activity in PhaseOut DMD. These
MRS-T2 findings show a positive impact on downstream muscle
health,” added Dr David Roblin, Chief Medical Officer and
President of R&D at Summit. “This, combined with the
evidence that ezutromid can modulate production of utrophin protein
and significantly reduce muscle damage, is further evidence of the
potential of ezutromid as a disease modifying approach for the
treatment of all genetic forms of DMD.”
[1] Arpan et al., Neurology, 2014, 83: 974-980.
[2] Willcocks et al., Neuromuscul Disord. 2014, 25(5): 393-401.
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 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 is a multi-centre trial that
enrolled 40 patients in the US and UK, aged from their fifth to
their tenth birthdays. PhaseOut DMD is 48 weeks in length after
which patients have the option of enrolling into an extension phase
and continuing to be dosed with ezutromid. 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. 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. Positive interim 24-week data were reported
in January 2018 that showed a significant and meaningful reduction
in muscle damage as measured by a decrease in levels of the
biomarker developmental myosin as measured by muscle biopsy.
PhaseOut DMD is going. Top-line 48-week results are expected to be
reported in the third quarter of 2018.
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 a 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).
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