MOR103 Presentation - MorphoSys
MOR103 Presentation - MorphoSys
MOR103 Presentation - MorphoSys
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Abstract-Number: L11<br />
First in Patient Study of Anti-GM-CSF Monoclonal<br />
Antibody (<strong>MOR103</strong>) in Active Rheumatoid Arthritis:<br />
Results of a Phase 1b/2a Randomized, Double-Blind,<br />
Placebo-Controlled Trial<br />
HARALD BURKHARDT<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Anti-GM-CSF Monoclonal<br />
Antibody (<strong>MOR103</strong>) in RA<br />
First in Patient Study of Anti-GM-CSF Monoclonal Antibody<br />
(<strong>MOR103</strong>) in Active Rheumatoid Arthritis: Results of a<br />
Phase 1b/2a Randomized, Double-Blind, Placebo-<br />
Controlled Trial<br />
Frank Behrens 1 , Mikkel Ostergaard 2 , Rumen Stoilov 3 , Piotr Wiland 4 , Thomas W.<br />
Huizinga 5 , Vadym Y. Berenfus 6 , Paul-Peter Tak 7 , Stoyanka Vladeva 8 , Juergen Rech 9 ,<br />
Andrea Rubbert-Roth 10 , Mariusz Korkosz 11 , Dmitriy Rekalov 12 , Igor A. Zupanets 13 ,<br />
Bo J. Ejbjerg 14 , Jens Geiseler 15 , Julia Fresenius 15 , Roman P. Korolkiewicz 16 , Arndt J.<br />
Schottelius 16 and Harald Burkhardt 1<br />
1 CIRI /Div. of Rheumatology, Goethe-University, Frankfurt/Main, Germany, 2 Copenhagen University Hospital at<br />
Glostrup, Glostrup, Denmark, 3 University Hospital (MHAT) St. Ivan Rilski, Sofia, Bulgaria, 4 Wroclaw Medical<br />
University, Wroclaw, Poland, 5 Leiden University Medical Center, Leiden, Netherlands, 6 Regional Clinical Hospital,<br />
Donetsk, Ukraine, 7 Academic Medical Center / currently also GlaxoSmithKline, Amsterdam, Netherlands, 8 Second<br />
Internal Clinic UMHAT Stara Zagora, Stara Zagora, Bulgaria, 9 University of Erlangen-Nuremberg, Erlangen, Germany,<br />
10 University of Cologne, Cologne, Germany, 11 Malopolskie Centrum Medyczne, Krakow, Poland, 12 Zaporizhzhia<br />
Regional Hospital, Zaporozhe, Ukraine, 13 Kharkiv, Ukraine, 14 Hospital at Slagelse, Slagelse, Denmark, 15 Asklepios<br />
Clinic Munich-Gauting, Gauting, Germany, 16 <strong>MorphoSys</strong> AG, Martinsried/Planegg, Germany<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Disclosures<br />
• F. Behrens, M. Ostergaard, R. Stoilov, P. Wiland, T. W. Huizinga, V. Y.<br />
Berenfus, S. Vladeva, J. Rech, A. Rubbert-Roth, M. Korkosz, D. Rekalov,<br />
I. A. Zupanets, B. J. Ejbjerg, J. Geiseler, J. Fresenius, H. Burkhardt are<br />
investigators on the <strong>MOR103</strong> study<br />
• P. P. Tak was a consultant to <strong>MorphoSys</strong> AG and is employee of<br />
GlaxoSmithKline<br />
• R. P. Korolkiewicz and A. J. Schottelius are employees of <strong>MorphoSys</strong> AG<br />
• The study was sponsored by <strong>MorphoSys</strong> AG<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
<strong>MOR103</strong> – Mechanism of Action<br />
Inflammation & Synovitis Structural Damage – Bone Erosion<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
© <strong>MorphoSys</strong> AG
Anti-GM-CSF Monoclonal<br />
Antibody (<strong>MOR103</strong>) in RA<br />
Phase 1b/2a Randomized, Double-Blind, Placebo-Controlled Trial<br />
• Trial design<br />
– Randomized, double-blind, placebo-controlled, multicentre<br />
– 96 treated patients with active moderate RA (DAS28≤5.1)<br />
– Dose regimen: 0.3, 1.0 and 1.5 mg/kg weekly x 4 injected intravenously<br />
vs. placebo<br />
– Pooled placebo patients across 3 cohorts<br />
• Primary outcome measures<br />
– Adverse event rate and safety profile<br />
• Secondary outcome measures<br />
– DAS28, ACR core set measures and EULAR response criteria,<br />
MRI (synovitis)<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Multinational Trial: Patient Recruitment<br />
Equally-Balanced Geographic Patient Distribution<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Total of n=96 patients treated
Study design<br />
0.3 mg/kg <strong>MOR103</strong> (n=25)<br />
Placebo (n=12)<br />
1.0 mg/kg <strong>MOR103</strong> (n=22)<br />
Placebo (n=7)<br />
DSMB<br />
safety review<br />
1.5 mg/kg <strong>MOR103</strong> (n=24)<br />
Placebo (n=8)<br />
DSMB<br />
safety review<br />
Follow up period (84 d)<br />
Follow up period (84 d)<br />
1 8 15 22 29 113 [day]<br />
Dose Administration<br />
n = randomized patients<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Follow up period (84 d)<br />
Cohort number, dose (mg/kg)<br />
period and monitoring<br />
Follow up period (84-days)<br />
DSMB safety review;<br />
Screening (to Cohorts 2 & 3)
Demographics<br />
Characteristic<br />
Age (median, yrs)<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Placebo<br />
N=27<br />
0.3 mg/kg<br />
N=24<br />
MOR 103<br />
1.0 mg/kg<br />
N=22<br />
1.5 mg/kg<br />
N=23<br />
54 57 51 52<br />
BMI (median, kg/m 2 ) 26.0 25.5 25.3 25.0<br />
Gender-Female 19 (70%) 21 (88%) 17 (77%) 18 (78%)<br />
Ethnic Origin: Caucasians 27 24 22 23
Baseline Disease Characteristics<br />
Characteristic #<br />
Placebo<br />
N=27<br />
0.3 mg/kg<br />
N=24<br />
MOR 103<br />
1.0 mg/kg<br />
N=22<br />
1.5 mg/kg<br />
N=23<br />
DAS28-ESR 4.88 4.88 4.78 4.87<br />
Serum CRP*<br />
baseline [mg/L]<br />
18.17 23.05 11.68 17.99<br />
ESR [mm/h] 28.7 28.1 21.9 24.9<br />
Swollen joint count 6.3 5.5 7.3 6.7<br />
Tender joint count* 9.4 8.0 12.3 11.3<br />
# mean<br />
* p
Concomitant treatment of RA<br />
Medication Class<br />
Placebo<br />
N=27<br />
0.3 mg/kg<br />
N=24<br />
MOR 103<br />
1.0 mg/kg<br />
N=22<br />
1.5 mg/kg<br />
N=23<br />
MTX 78% (21) 75% (18) 64% (14 ) 83% (19 )<br />
Other DMARD # 22% (6) 17% (4 ) 18% (4) 9% (2 )<br />
Glucocorticosteroids 70% (19) 83% (20) 64% (14) 65% (15)<br />
NSAIDS 48% (13) 54% (13 ) 59% (13) 52% (12)<br />
# Sulfasalazine, Hydroxychloroquine, Leflunomide<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Patient Disposition<br />
Placebo<br />
(n=27)<br />
Prematurely terminated (n=5)<br />
AE (n=1)<br />
Consent withrawn (n=2)<br />
Other (n=2)<br />
Completed study<br />
(n=22)<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
<strong>MOR103</strong> 0.3 mg/kg<br />
(n=25)<br />
Randomized not treated (n=1)<br />
Prematurely terminated (n=3)<br />
Non-permitted therapy (n=1)<br />
Start of new RA treatment (n=1)<br />
Other (n=1)<br />
Completed study<br />
(n=21)<br />
Randomized<br />
(n=98)<br />
Screened<br />
(n=288)<br />
<strong>MOR103</strong> 1.0 mg/kg<br />
(n=22)<br />
Prematurely terminated (n=3)<br />
Non-permitted therapy (n=2)<br />
Start of new RA treatment (n=1)<br />
Completed study<br />
(n=19)<br />
Failed to meet inclusion<br />
criteria<br />
(n=190)<br />
<strong>MOR103</strong> 1.5 mg/kg<br />
(n=24)<br />
Randomized not treated (n=1)<br />
Prematurely terminated (n=0)<br />
Completed study<br />
(n=23)
Most Common TEAEs<br />
Subjects with TEAEs by Preferred Term<br />
Adverse Event<br />
Preferred Term<br />
Subj. with at least<br />
one TEAE<br />
Placebo<br />
N=27<br />
Total active<br />
N=69<br />
0.3 mg/kg<br />
N=24<br />
MOR 103<br />
1.0 mg/kg<br />
N=22<br />
1.5 mg/kg<br />
N=23<br />
Placebo vs<br />
Total Active<br />
(Fisher‘s<br />
Exact Test)<br />
44.4% (n=12) 60.9% (n=42) 54.2% (n=13) 63.6% (n=14) 65.2% (n=15) 0.1733<br />
related 25.9% (n=7) 14.5% (n=10) 12.5% (n=3) 13.6% (n=3) 17.4% (n=4) 0.2357<br />
Nasopharyngitis 11.1% (n=3) 13.0% (n=9) 4.2% (n=1) 31.8% (n=7) 4.3% (n=1) >0.9999<br />
Rheumatoid<br />
Arthritis worsening<br />
related 7.4% (n=2) 1.4% (n=1) 4.2% (n=1) 0.0% (n=0) 0.0% (n=0) 0.1900<br />
0.0% (n=0) 13.0% (n=9) 12.5% (n=3) 18.2% (n=4) 8.7% (n=2) 0.0574<br />
related 0.0% (n=0) 1 (1.4%) 0.0% (n=0) 4.5% (n=1) 0.0% (n=0) >0.9999<br />
Fatigue 3.7% (n=1) 8.7% (n=6) 4.2% (n=1) 18.2% (n=4) 4.3% (n=1) 0.6690<br />
related 0.0% (n=0) 4.3% (n=3) 4.2% (n=1) 4.5% (n=1) 4.3% (n=1) 0.5567<br />
Hypertension 3.7% (n=1) 7.2% (n=5) 4.2% (n=1) 9.1% (n=2) 8.7% (n=2) >0.9999<br />
related 0.0% (n=0) 1.4% (n=1) 0.0% (n=0) 4.5% (n=1) 0.0% (n=0) >0.9999<br />
Cough 0.0% (n=0) 4.3% (n=3) 4.2% (n=1) 0.0% (n=0) 8.7% (n=2) 0.5567<br />
related 0.0% (n=0) 0.0% (n=0) 0.0% (n=0) 0.0% (n=0) 0.0% (n=0) >0.9999<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
ACR Response at Week 4<br />
Percentage of Patients achieving ACR 20, ACR 50, ACR 70<br />
Proportion of Responders [%]<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Mean change from baseline<br />
ACR-Subcomponent Analysis<br />
Mean Change of Swollen and Tender Joints from Baseline<br />
Swollen joints Tender joints<br />
*<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
*<br />
*<br />
*<br />
*<br />
**p
EULAR Response at Week 4<br />
Percentage of Patients achieving EULAR Response<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
**<br />
**<br />
**p=0.0001
DAS28: Mean Changes from Baseline<br />
Response over Time<br />
Mean change from baseline<br />
treatment period<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
* *<br />
**<br />
**<br />
Week<br />
*<br />
*<br />
*<br />
*<br />
**p
Change of Synovitis by MRI Analysis<br />
RAMRIS score of the dominantly affected hand at week 4<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Mean change from baseline<br />
RAMRIS Sum-Scores at Week 4
Conclusions<br />
• <strong>MOR103</strong> showed favorable safety data in all active<br />
treatment groups<br />
• <strong>MOR103</strong> showed promising therapeutic activity<br />
• Consistent responses seen in clinical parameters<br />
• Rapid onset of therapeutic effect within 2 weeks<br />
• Sustained response up to 10 weeks beyond treatment<br />
• The 1.0 mg/kg group demonstrates the efficacy<br />
potential of <strong>MOR103</strong><br />
• Imaging supports anti-inflammatory activity of<br />
<strong>MOR103</strong><br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Acknowledgements<br />
Investigators<br />
� Bulgaria:<br />
• A. Batalov; I.Goranov; V. Kadinov; I. Kazmin; R. Rashkov;<br />
� Germany:<br />
• R. Alten; G. Burmester; M. Fleck; I. Koetter; U. Müller-Ladner; H.<br />
Soerensen; S. Wagner; U. Wagner<br />
� The Netherlands:<br />
• D. Gerlag<br />
� Poland:<br />
• M. Brzosko; J. Gaweda; J. Glogowska-Szelag; P. Hrycaj; S. Jeka; M. Krogulec;<br />
B. Kwiatkowska; M. Mazurek; J. Olas; M. Stopinska-Polaszewska<br />
� Ukraine:<br />
• K. Amosova; O. Dyadyk; V. Kovalenko; B. Palamar; S. Smiyan; M. Vatutin<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012
Thank you for your attention!
Geographic Distribution of Patients<br />
Well Balanced between Treatment Groups<br />
Total<br />
Bulgaria<br />
Germany<br />
Netherlands<br />
Poland<br />
Ukraine<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Placebo<br />
<strong>MOR103</strong><br />
0.3 mg/kg 1.0 mg/kg 1.5 mg/kg<br />
27 24 22 23<br />
6 12 7 4<br />
4 4 7 2<br />
2 0 0 1<br />
8 8 4 3<br />
7 0 4 13
ACR-Subcomponent Analysis ESR [mm/hour]<br />
Median Changes from Baseline<br />
Median change from<br />
baseline<br />
treatment period<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012<br />
Visit (week)
DAS28 Response to Treatment<br />
<strong>MOR103</strong> vs Placebo at Day 29 and 57<br />
ACR/ARHP 2012 – Washington DC – November 10-14, 2012