ABLYNX ANNOUNCES NEW COMPELLING RESULTS ON OZORALIZUMAB (ATN-103) IN RHEUMATOID ARTHRITIS
Additional Phase II data (ACR20 84%; DAS28 remission 38%) demonstrates that ozoralizumab could have an important competitive and differentiated position in the $24 billion TNFα market
Data from the open-label study suggest that ozoralizumab enables individualised treatment, a real breakthrough in TNFα therapy, which could prove beneficial to patients and minimise the treatment cost
Immunogenicity did not affect the efficacy of ozoralizumab, while it is known to have a big impact on the efficacy of Humira®, the world's biggest selling anti-TNFα drug
GHENT, Belgium, 25 June 2012 - Ablynx [Euronext Brussels: ABLX], today announced that its anti-TNFα Nanobody, ozoralizumab (ATN-103), for the treatment of inflammatory diseases, showed excellent safety and efficacy results in the 48-week open-label extension (OLE) study of the worldwide and Japanese Phase II trials in the treatment of patients with Rheumatoid Arthritis (RA) who have an insufficient response to methotrexate alone.
Dr Edwin Moses, Chairman and CEO of Ablynx, commented:
"We always believed in this programme and now the data from this long-term study have even positively surprised us. We now have extensive efficacy data that are potentially as good, if not better, than other commercially available anti-TNFα products (and this is a $24 billion market) and, in terms of immunogenicity, an unexpected and potentially major advantage over Humira®, the world's biggest selling anti-TNFαand any of its biosimilar competitors that may be launched in the future. We believe that we now have the components of a much stronger and differentiating licensing package than we had previously."
A total of 266 patients (85%) from the previous two Phase II studies rolled-over into the open-label extension study (which was fully funded by Pfizer) and were treated with ozoralizumab by a subcutaneous (sc) injection every four weeks (Q4W) for an additional 48 weeks on top of methotrexate. Following a washout period of eight to twelve weeks during which no study-drug was administered, all patients started with a dose of 10 mg Q4W and subsequent doses could be escalated, dependent on their physician's assessment, to 30 mg and then 80 mg Q4W. A total of 86% of patients completed the study: 56% of the patients completed the study at 80 mg Q4W, 29% of the patients completed the study after a single dose escalation step to 30 mg Q4W, and 15% of the patients stayed at their starting dose of 10 mg Q4W.
Only 2.6% of patients (7/266) tested positive for neutralising anti-drug antibodies (nADAs) at any time during the 48 week study and all of them completed the trial, with 57% (4/7) of these patients achieving DAS28 remission. Moreover, only 0.75% of patients remained positive for nADAs at the end of the treatment period. Humira® (adalimumab), the leading commercialised anti-TNFαproduct (and expected to be the world's top selling drug in 20121) states on its label2 that it may produce neutralising antibodies in 1-12% of patients within one year of treatment, though recent data suggest that this number may be considerably higher and up to 35%3. In addition the label states that formation of anti-adalimumab antibodies is associated with reduced efficacy, which is confirmed in a recent publication4 to result in a diminished treatment response (only 4% of patients with nADAs achieved DAS28 remission), hence the need to switch to another drug regimen over time.
The most common adverse events associated with ozoralizumab treatment were infections. Of these, only 3 events per 100 patient years were serious, which is comparable to those seen with other TNFα drugs, indicating that ozoralizumab has a promising safety profile. An average reported number of 4.7 events per 100 patient years is reported for all currently marketed TNFα blockers5.
The following results refer to the study population that completed the study treatment and results are pooled for all patients who started at 10 mg and either stayed at 10 mg or subsequently received monthly injections of 30 mg and 80 mg.
Efficacy parameter
Week 48 (N=230)
ACR20
84%
ACR50
63%
ACR70
32%
Clinical remission (DAS28<2.6)
38%
The ACR6 scores were highly comparable to reported OLE Phase II data from other TNFα blockers. Moreover, for patients who responded well on ozoralizumab in the proof-of-concept trial and entered the open-label extension study with low or no disease activity, doses starting as low as 10 mg monthly were sufficient to improve or maintain the patient's response throughout the 48 weeks study period, suggesting the possibility of individualised dosing based on a patient's disease activity and weight, which could offer important health economic and patient safety benefits.
With a mean improvement of 3.11 in the overall DAS287 score, a large proportion (38%) of patients achieved the criteria for disease remission (i.e. no signs of disease activity), the ultimate treatment goal.
1 Consensus forecasts compiled by Thomson Reuters Pharma
2 http://www.rxabbott.com/pdf/humira.pdf
3 Ann Rheum Dis (2007) 66: 921-926, Rheumatol Int (2007) 27: 269-274, JAMA 305(14):1460; EULAR 2012 AB0055
4 JAMA 305(14):1460
5 Internal data compilation based on public sources
6 ACR criteria measure improvement in tender or swollen joint counts and improvement in three of five other disease-activity measures; ACR20 measures % of patients with 20% improvement; ACR50 measures % of patients with 50% improvement and ACR70 measures % of patients with 70% improvement
7 DAS28 is an RA disease activity score based on C-reactive protein (CRP), tender and swollen joint counts of 28 defined joints and physician's global health assessment; a total score of >5.1 is associated with high disease activity, moderate from 3.2 to 5.1, low disease activity from 2.6, and remission of disease if <2.6
Already at week 12, patients achieved a 70% and 62% reduction in swollen and tender joint counts respectively, with 61% of all patients showing at least one measure of no or low disease activity8.
Conference call and webcast presentation
The Ablynx management team will host a conference call and webcast during which the results from the open-label extension study for ozoralizumab will be presented, followed by a Q&A session. This event will be held today, 25 June 2012 at 14h CET/ 8 am EST. The conference call will be webcast live and may be accessed on the home page of the Ablynx website at www.ablynx.com or by clicking here. If you would like to participate in the Q&A, please dial +32 (0)2 789 21 26. Shortly after the call, a replay of the webcast and the presentation used in connection with the conference call webcast will be available on the Company's website.
About ozoralizumab (ATN-103)
Ozoralizumab is a trivalent, bi-specific Nanobody that potently neutralises TNFα and binds to human serum albumin to increase its in vivo half-life. The Nanobody format has a number of significant advantages over the currently available TNFα inhibitors. It does not have an Fc domain ('antibody tail'), and hence is not expected to engage the patient's immune system. Its smaller size and the fact that ozoralizumab binds to human serum albumin could lead to an improved tissue penetration, for instance to inflamed joints. Its physicochemical properties allow for high concentration of the final drug product and for alternative routes of administration other than just injection.
In May 2011, ozoralizumab achieved clinical proof-of-concept in a worldwide (excluding Japan) Phase II study in 253 patients with active RA on a stable background of methotrexate.
About Ablynx Ablynx is a biopharmaceutical company engaged in the discovery and development of Nanobodies®, a novel class of therapeutic proteins based on single-domain antibody fragments, for a range of serious human diseases, including inflammation, haematology, oncology and pulmonary disease. Today, the Company has over 25 programmes in the pipeline and seven Nanobodies are at clinical development stage. Ablynx has ongoing research collaborations and significant partnerships with major pharmaceutical companies, including Boehringer Ingelheim, Merck Serono, and Novartis. The Company is headquartered in Ghent, Belgium. More information can be found on www.ablynx.com.
For more information, please contact
Ablynx:
Dr Edwin Moses
Chairman and CEO
t: +32 (0)9 262 00 07
m: +44 (0)7771 954 193 / +32 (0)473 39 50 68
e: [email protected]
Marieke Vermeersch
Investor Relations Manager
t: +32 (0)9 262 00 82
m: +32 (0)479 49 06 03
e: [email protected]
Follow us on Twitter (#AblynxABLX), LinkedIn and Facebook
8 Low or no disease activity: at least one of the following: DAS28 <2.6; no joint disease activity (no swollen or tender joints); clinical remission (indicated by 1 tender or swollen joint and CRP of 1mg/dl or less)
M:Communications:
Mary-Jane Elliott, Amber Bielecka, Claire Dickinson
t: +44 207 920 2330
e: [email protected]
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