Bristol-Myers Squibb has presented promising mid-stage data on its investigational rheumatoid arthritis drug clazakizumab which shows it is as effective as AbbVie's blockbuster Humira.

In the 418-patient Phase IIb trial, the results from which were presented at the American College Of Rheumatology meeting in San Diego, participants on clazakizumab doses ranging from 25-200mg monotherapy and in combination with methotrexate were studied versus MTX alone, while Humira (adalimumab) in combination with MTX was included as an active reference arm.

All clazakizumab arms, alone or in combination with MTX, demonstrated efficacy in controlling the signs and symptoms of RA, and met the primary endpoint of a higher ACR20 response rate (ie a 20% improvement in the condition) versus MTX alone after 12 weeks of treatment.

Specifically, 78% of patients on clazakizumab 25mg plus methotrexate saw a 20% reduction, compared with 39.3% for MTX alone, while the ACR20 response rate for adalimumab 40mg plus MTX was 76.3%. However, by week 24, ACR70 (70% reduction) rates ranged from 27.1% to 38.3% in the clazakizumab combo versus 6.6% for MTX alone and 18.6% for Humira plus MTX. Also of note were the remission rates for B-MS' human anti-interleukin (IL)-6 monoclonal antibody plus MTX; up to 23.3% compared with 8.5% for the Humira/MTX combo.

'Extremely effective new molecule'

Investigator Paul Emery, director of MSK Biomedical Unit at the Leeds Teaching Hospitals Trust in the UK, said "there is a great need for additional disease-modifying therapies that can provide more patients with deep and sustainable remission, helping preserve function and limit further joint damage". He told PharmaTimes that clazakizumab is "an extremely effective new molecule", which works through blocking IL-6 but acts directly on the cytokine rather than indirectly via the receptor, "which may have differences regarding the relative safety and efficacy of the drug".

Dr Emery noted that the target of blocking IL-6 is the same as Roche's already-marketed blockbuster Actemra (tocilizumab), but the method of doing it is unique. In a separate preclinical study of in-vitro assays, also being presented at the ACR, clazakizumab was shown to bind to the IL-6 cytokine with high affinity and block various IL-6-induced functions more potently than Actemra

He went to say that the drug has shown very impressive data, "some of the highest response rates seen at this phase of a drug", noting that remission rates are high (currently less than 30% of RA patients experience sustained remission as defined by ACR criteria) and "it was compared with the best-selling drug combination in rheumatology".

His enthusiasm was echoed by Pushkal Garg, vice president of clinical development for immunoscience at B-MS. He told PharmaTimes the company was pleased to meet the primary endpoint while showing promising data with some of the remission endpoints "and to be able to do this with a once-a-month sub-cutaneous administration is very exciting".

Clazakizumab has sneaked under the radar somewhat and Dr Garg noted that data from a Phase IIa study was presented in Europe two years of an intravenous form of the drug. The SC version will be going into Phase III and "we are going through all the data very carefully and mapping out the next steps". Along with the new drug and the blockbuster Orencia (abatacept), "we are building an RA franchise," he concluded.

Bristol-Myers bought the rights to develop clazakizumab for all indications other than cancer from Alder Biopharmaceuticals in 2009 in a deal that could be worth over $1 billion to the latter.