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June 28, 2016

Assay could represent big breakthrough in MS

Dr Carmen Bozic

A promising assay could reduce the risk of serious brain infection in MS patients on Tysabri, Senior Vice President and Global Head, Drug Safety and Risk Management, for Biogen Idec Dr Carmen Bozic tells Lloyd Mudiwa

An investigational assay that detects anti-JC virus (JCV) may provide a means to determine which multiple sclerosis (MS) patients can safely receive Tysabri (natalizumab) with significantly reduced risk of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection.

According to data published in the New England Journal of Medicine, Tysabri treatment, after two years, led to a 68 per cent relative reduction in the annualised relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54 per cent, Senior Vice President and Global Head, Drug Safety and Risk Management, for Biogen Idec Dr Carmen Bozic said.

While Tysabri has advanced the treatment of MS patients with its established and powerful efficacy, its use does increase the risk of PML, an opportunistic viral infection that may lead to death or severe disability.

However, if the test were approved, it would help screen patients at a higher risk of getting PML, Dr Bozic explained.

Infection with JCV is one of a number of factors required for the development of PML. Detection of anti-JCV antibodies may be a useful tool to identify prior or ongoing JCV infection, and help physicians to better assess a patient’s potential risk for developing PML.

Exclusive data
Speaking over the phone from Massachusetts, Dr Bozic told Irish Medical Times about exclusive new data that further support the potential clinical utility of the assay that detects anti-JCV antibodies in human plasma or serum and might provide the means to segment MS patients considering receiving treatment with Tysabri and assess their risk for developing PML.

“Our hypothesis is that those who have antibodies may have perhaps up to double the risk, but those who don’t have a reduced risk. So that’s the really good news,” said Dr Bozic.

The two-step, analytically-validated, enzyme-linked immunosorbant assay (ELISA) to detect anti-JCV antibodies is currently being evaluated in large-scale, prospective clinical studies involving more than 10,000 patients from all over the world in order to determine the utility of the assay in stratifying the risk of PML in Tysabri-treated patients.

Biogen Idec and Elan Corporation first announced data supporting the potential of the assay at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Gothenburg, Sweden, in September. Biogen told delegates at the congress about factors associated with anti-JCV antibody prevalence in a large cohort of natalizumab-treated MS patients.

Dr Bozic, who has led the development of the risk management plan for Tysabri, outlined that ELISA was used to detect anti-JCV antibodies in blood from patients enrolled in the Tysabri Global Observation Study (TYGRIS), and the Safety of Tysabri Re-dosing and Treatment (STRATA) and JCV Antibody Program in Patients with Relapsing Multiple Sclerosis Receiving or Considering Treat-ment with Tysabri (STRATIFY-1) studies. This was followed by a chi-square test used to assess associations between factors and prevalence of anti-JCV antibodies.

Together, the data from TYGRIS, STRATA and STRATIFY-1 represent one of the largest cohorts of MS patients evaluated for the presence of anti-JCV antibodies, demonstrating an overall prevalence of anti-JCV antibodies of approximately 50 to 60 percent and delineating the prevalence by factors such as age and gender.

Furthermore, the use of Tysabri and prior treatment with immunosuppressant did not appear to affect the prevalence of anti-JCV antibodies in this cohort.

Another study, which used the ELISA to evaluate more than 800 serum samples, was designed to assess the prevalence of anti-JCV antibodies in Tysabri-treated MS patients and evaluate the possible utility of anti-JCV antibodies as a means to segment, or stratify, MS patients and assess their risk for developing PML, Dr Bozic explained.

“Of the more than 800 patients evaluated, 54 per cent tested positive for anti-JCV antibodies,” she stated.

“Additionally, anti-JCV antibodies were detected in 20 out of 20 [100 per cent] of Tysabri-treated PML patients at least six months prior to the diagnosis of PML.”

Three laboratories had then evaluated precision, including specificity and sensitivity, of the assay. “The ability of ELISA to detect anti-JCV antibodies was robust and cross-validated by all three laboratories.

“The assay is now being used in two global clinical trials to evaluate the potential clinical utility of anti-JCV antibody status for stratifying PML risk.”

Dr Bozic said Biogen would try to make this assay more broadly acceptable and was now working to review data for its review over the next few months. “The next step,” she said, “is to submit an application in America and in Europe; then it would be up to the regulators.”

The company has had a lot of feedback from physicians who are interested and want Biogen to bring out the assay, so there was a lot of excitement at ECTRIMS. “It is something that physicians would welcome as it would be able to help them assess a patient’s risk for developing PML and in making a benefit risk assessment as to what is the best MS therapy for their patients. They are very excited about Tysabri and the promise of this assay,” said Dr Bozic.