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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 but 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-TNF 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-TNFand 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-TNFproduct (and expected to be the world’s top selling drug in 2012) states on its label 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%. In addition the label states that formation of anti-adalimumab antibodies is associated with reduced efficacy, which is confirmed in a recent publication 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 blockers.
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)
Clinical remission (DAS28<2.6) 38%
The ACR 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 DAS28 score, a large proportion (38%) of patients achieved the criteria for disease remission (i.e. no signs of disease activity), the ultimate treatment goal. 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 activity.
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.
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.
Tags: clinical trials