Excellent Interim Results Reported From Phase I/II Study With Anti-IL-6R Nanobody, ALX-0061, In Rheumatoid Arthritis Patients
Ablynx [Euronext Brussels: ABLX] has announced that its anti-IL-6R Nanobody, ALX-0061, met the efficacy endpoint of a significant improvement in key indicators of disease activity at the 12 week interim analysis of the Phase I/II study in patients with moderate to severe active rheumatoid arthritis (RA) on a stable background of methotrexate. Final 24 week results are expected in the first quarter of 2013.
In this Phase I/II study, 37 RA patients were recruited to the multiple dose Phase II part. Patients were randomised to three dose groups of intravenously administered ALX-0061 (1mg/kg every 4 weeks, 3mg/kg every 4 weeks and 6mg/kg every 8 weeks) or to placebo. At the week 12 interim analysis, the 3mg/kg dose level of ALX-0061 met the efficacy endpoint in achieving statistically significant improvement in DAS28 remission and ACR20 scores compared with placebo. Moreover, all dose groups showed impressive results in all efficacy endpoints, with a DAS28 remission of >40% achieved consistently at week 8 and with an onset of remission observed in some patients already at week two.
At all doses tested, ALX-0061 was well-tolerated and the safety profile compared favourably to data reported for other biological DMARDs. Additionally, no decrease in neutrophils (white blood cells), no clinically significant increases in liver enzymes and no increases in lipid levels (cholesterol) were observed at the interim analysis.
A total of 34 subjects were eligible for determination of the efficacy endpoints at week 12:
|Efficacy parameter||1mg/kg every 4 weeks (N=9)||3mg/kg every 4 weeks (N=10)||6mg/kg every 8 weeks (N=9)||Placebo (N=6)|
Dr Josefin-Beate Holz, Chief Medical Officer of Ablynx, commented: “We are extremely pleased with the results from the first 12 weeks of this study. The observed high clinical remission in combination with the very encouraging safety profile demonstrates that ALX-0061 is potentially unique and differentiated compared with monoclonal antibodies that target the IL-6 pathway.”
Dr Edwin Moses, Chairman and CEO of Ablynx added: “We believe that ALX-0061 could become a very valuable alternative treatment option for patients with RA. Efficacy, safety and convenience of administration are key to patients and payers, and ALX-0061 has the potential to offer important advantages in all these areas. We anticipate that these data will generate a lot of interest and trigger a number of pharma companies to initiate partnering discussions. This is our second clinical proof-of-concept for a Nanobody and further emphasizes the potential value of our clinical assets. It also reinforces the power and breadth of our unique technology platform, building on the recent successful first pulmonary delivery of a Nanobody (ALX-0171 in RSV).”
About ALX-0061 (anti-IL-6R)
ALX-0061 is a 26kD Nanobody that binds to both the soluble and membrane-bound interleukin-6 receptor (IL-6R). ALX-0061 is half-life extended with a Nanobody targeting albumin, which is believed to improve the delivery of the Nanobody to inflamed tissues.
The involvement of the IL-6 pathway in a variety of diseases indicates that multiple indications can be pursued with a large market potential including rheumatoid arthritis (RA), Crohn’s disease, Castleman’s disease, multiple myeloma and systemic lupus erythematosus (SLE). Blocking the IL-6 pathway is becoming the preferred second line biological treatment. (Ro)Actemra® (Roche) is the only anti-IL-6R biological on the market and its sales are expected to increase to $2.2bn in 2015.
Final results from the Phase I/II study at week 24 with ALX-0061 in patients with active RA are expected during the first quarter of 2013.
*p<0.05 – descriptive statistical analyses 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
 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
 DMARDs: disease modifying anti-rheumatoid arthritis drugs
 Three patients withdrew prior to week 12 assessment