Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Ozoralizumab (ATN-103), a novel TNFα inhibitor, is a trivalent, bispecific Nanobody® that potently neutralises TNF and binds to human serum albumin to increase its in vivo half-life. 2 singe ascending dose (SAD)/ multiple ascending dose (MAD) studies in 313 patients (world-wide and Japan) with active RA on stable MTX background evaluated ozoralizumab’s clinical activity and safety during 12 weeks of treatment. The 80mg Q4W dosing regimen significantly improved disease activity measures compared with placebo. Patients completing the MAD trials were allowed to enrol in this 48-week open-label extension (OLE) study to evaluate the long-term safety and tolerability of ATN-103. An innovative dosing concept with individual dose escalation from 10mg to max. 80mg during first 12 weeks of treatment was tested in this OLE.
Methods:
Study start was defined as completion of 20-week follow-up visit in the MAD trials. Individualized dosing regimen was introduced with all patients starting on active treatment at 10mg SC monthly. Subsequently, dose escalation to 30mg and 80mg monthly SC was dependent on patient’s CDAI and safety. Primary objective was long-term safety and tolerability of ATN-103. Efficacy measures, as well as PK/PD, were included as exploratory endpoints.
Results:
266/313 pat (85%) enrolled in the OLE. Baseline mean age was 52y, 80% female, DAS 6.11 and CDAI 42. Dropout rate was low with 13% and 231/266 pat completed the study. 93% of pat reached individual final dose at or before week 12, 56% completed at 80 mg, 29% at 30mg and 15% remained on the starting dose of 10mg. Safety: Treatment was well tolerated, most common AEs were infections (37.6%) with serious events in 3/100 pat years. Efficacy: At study endpoint, ACR20, 50 and 70 scores were 84%, 63% and 32% respectively; 38% had DAS28_CRP <2.6; 132/230 pat (57%) had low or no disease activity; EULAR good/moderate response rate was 97% with rapid and marked improvement of pain (47%) and morning stiffness (90%). 7/266 pat tested positive for neutralizing anti-drug antibodies (nADA) at any time during trial, all completed the study and 57% (4/7) had DAS28 <2.6. 0.75% of patients remained positive for nADA at end of study without effect on patient’s safety or ability to achieve remission or improvement of disease activity.
Conclusion:
The novel anti-TNFα inhibitor ATN-103 enabled highly effective and well-tolerated individualized treatment. Specific molecular features of Nanobodies (small size, low immunogenicity potential, manufacturability) contributed to the desired treatment outcome with the majority of patients showing marked improvement in their disease activity and, moreover, once induced remission could be maintained at doses less than 80mg monthly. This treatment approach could prove beneficial to patients and minimize treatment costs.
Disclosure:
R. Fleischmann,
Genentech Inc, Roche, Abbott, Amgen, UCB, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen,
2,
Roche, Abbott, Amgen, UCB, Pfizer, BMS, Lilly, Sanofi Aventis, Lexicon, Novartis, Astellas, Astra-Zeneca, Jansen, HGS,
5;
S. De Bruyn,
Ablynx N.V.,
1,
Ablynx N.V.,
3;
C. Duby,
Ablynx NV,
3,
Ablynx NV,
1;
K. Verschueren,
Ablynx N.V.,
1,
Ablynx N.V.,
3;
J. Baumeister,
Ablynx N.V.,
1,
Ablynx N.V.,
3;
L. Sargentini-Maier,
Ablynx NV,
1,
Ablynx NV,
3;
C. Ververken,
Ablynx N.V.,
1,
Ablynx N.V.,
3;
J. B. Holz,
Ablynx N.V.,
1,
Ablynx N.V.,
3,
Ablynx N.V.,
6.
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-individualized-treatment-approach-in-open-label-extension-study-of-ozoralizumab-atn-103-in-subjects-with-rheumatoid-arthritis-on-a-background-of-methotrexate/