FDA-Approved Medications: New Data
Company: Biogen and AbbVie
- 150 mg given via subcutaneous injection once monthly
- Approved in May 2016 for RMS
Zinbryta® (daclizumab) joined the arsenal of FDA-approved medications for RRMS in 2016. Zinbryta is a genetically engineered monoclonal antibody that binds to CD25, a receptor on T cells that is thought to become activated in response to MS. Zinbryta is believed to work by selectively targeting these activated T cells without causing general T-cell depletion. It is approved by the FDA for use in rheumatoid arthritis and other autoimmune diseases. Daclizumab high-yield process (DAC HYP) is administered subcutaneously once every four weeks, rather than via IV infusion.
Participants in the Phase II CHOICE study had either RRMS or SPMS, with worsening disease activity while taking one of three approved interferon therapies. The study showed that DAC HYP was well tolerated when added to an interferon. A statistically significant 72-percent reduction in the frequency of gadolinium-enhancing MRI lesions was seen in the high-dose group (300 mg every four weeks).
The Phase IIb SELECT trial, with 600 participants who have RRMS, was a one-year study of treatment with DAC HYP. This study was subsequently extended for a second year as the SELECTION trial. The study included three treatment arms, with two dose levels (at 150 mg and 300 mg) and a placebo group (given an inactive treatment).
Results of the SELECT trial announced in August 2011 indicated that the annualized relapse rate was decreased by 54 percent in the 150 mg-dose group and by 50 percent in the 300 mg-dose group. It also met its secondary endpoints: in the 150 mg and 300 mg groups respectively, new gadolinium-enhancing lesions were reduced by 69 percent and 78 percent; new or newly enlarging T2-hyperintense lesions were reduced by 70 percent and 79 percent; and the proportion of patients who relapsed was reduced by 50 percent and 51 percent. Sustained disability progression at one year was reduced by 57 percent and 43 percent.
Participants who completed this trial were enrolled in an extended trial called SELECTION. One-year results were presented4 in 2012. Patients who were on placebo and began treatment with DAC HYP in the extension trial had a 59-percent reduction in annualized relapse rate compared to the year prior, while patients who continued on DAC HYP maintained their low relapse rate from the prior year.
In 2013, further data from this trial were presented.5 During the second year of treatment, brain-volume loss (atrophy) was 27-percent lower in the treated groups compared with the placebo group at year one. The authors of the study note that this reduction in the rate of brain atrophy may be consistent with neuroprotection.
DAC HYP was further studied in the DECIDE trial,6 a Phase III study of 1,841 participants with relapsing MS, comparing DAC HYP to Avonex® (interferon beta-1a). DAC HYP was administered subcutaneously once every four weeks for 96 to 144 weeks with a dose of 150 mg. This was compared to a weekly 30-mcg intramuscular injection of Avonex. The study began in March 2010 and was completed in the spring of 2014.
Initial results of the DECIDE trial were presented in 2014. Treatment7 with daclizumab resulted in a 45-percent reduction in annualized relapse rate (ARR), a 54-percent reduction in new and newly enlarging T2 lesions, and a 65-percent reduction in new gadolinium-enhancing lesions in comparison to Avonex. Risks associated with daclizumab treatment included infections, rash dermatitis, and liver enzyme abnormalities, some of which were serious. More than a third of people on daclizumab reported cutaneous (skin) issues – twice as many as on Avonex – including some cases severe enough to warrant discontinuing the drug. One death of a daclizumab-treated patient from the Phase II study was due to complications of a muscle abscess, and a second death was due to autoimmune liver inflammation. The safety profile of this medication, including the nature of the cutaneous (skin) side effects, will be closely evaluated in further analyses.
In abstracts presented at the 2015 ECTRIMS meeting, DAC HYP was shown to be more effective in patients at risk for high disease activity, as well as for those with less active disease, compared to individuals taking Avonex. Over the course of three years, DAC HYP was also associated with less brain-volume loss with RRMS, compared to individuals taking interferon beta-1a. The safety profile has been well characterized in clinical studies for periods up to six years.
By testing approved medications for relapsing MS in progressive disease, the possibility of extending the use of these well-known medications for progressive MS may be rigorously explored. Unfortunately, as discussed in the following sections on Tysabri and Gilenya, success in relapsing MS does not always predict similar efficacy in those with progressive disease.