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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

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