Without disclosing details, Ablynx announced that it successfully finished the phase I part of the phase I/II study with ALX-0061, an anti-IL-6R Nanobody, in rheumatoid arthritis (RA) patients. Based on the positive results, the project moved into the phase II part of the study, also in RA patients.
Our View:
In the phase I part, 20 RA patients received a single dose ranging from 0.3mg/kg to 6 mg/kg (previously 8mg dose was foreseen, but the maximum predicted effect was already seen at 6mg), 8 patients received placebo. The results showed that ALX-0061 was safe and well tolerated, and Ablynx reported that the ‘dose-dependant changes of the assessed biomarkers (CRP, fibrinogen and platelets) were consistent with the inhibition of the IL-6 pathway’. In more common language, that means that the indicator of inflammation (CRP) rapidly and consistently decreased, which is positive. The fibrinogen and blood platelet counts also decreased. We understand platelets did not decrease to clinically significant levels, and are considered as sign of drug activity. Blocking the IL-6 pathway for the treatment of inflammation is a validated mode of action, with Roche’s Actemra being the proof (mainly used for patients not responding to TNF-alpha therapy). However, Actemra does suffer from side effects, and concerns have been raised on the low neutrophil count, low platelet count, increased liver enzymes and increased in blood cholesterol levels. Hence, the reason why it is important to closely monitor for IL-6-pathway modulating drugs, but also because an improved safety profile could provide a competitive advantage over Actemra. So far, the phase I study did not show clinical signs of toxicity and the most meaningful safety results will only be available (and released) after the phase II study is finished.
In the phase II part, around 36 patients will receive multiple doses of ALX-0061 (1m/kg every 4 weeks, 3 mg/kg every 4 weeks and 6 mg/kg every 8 weeks) or placebo (so an average 9 patients per arm). A first reporting will be done after 12 weeks (including DAS and ACR scores) and the final read-out after 24 weeks. The study will recruit patients in 3 CEE countries, not responding to methotrexate and with moderate to severe DAS28 scores. Given the small number of patients and the inclusion criteria, we expect the interim results by the June-July 2012 timeframe and final data by 4Q12.
Conclusion:
The positive phase I outcome and the move towards phase II are in-line with expectations. With ALX-0061, Ablynx has next to its recently regained TNF-alpha program, another shot on goal to find a commercially viable RA treatment. The IL-6 mode of action is validated, but the market is not as crowed as the TNF-alpha market. Moreover, there is room for improvement versus current commercial and development products, both from a safety and dosing/administration perspective. Ablynx’ small phase II trial design should provide by mid-year 2012 the first indications if ALX-0061 has the potential to provide unique advantages, and bring the company back in pool position.