Daclizumab HYP Shows Favorable Risk/Benefit Profile in Clinical Trials

Immunomodulatory drugs, including humanized monoclonal antibodies, have been shown to modify the disease course for individuals with multiple sclerosis (MS). Daclizumab high-yield process (DAC HYP) is one such monoclonal antibody that is in phase 3 clinical trials for individuals with relapsing-remitting MS (RRMS).

Safety and tolerability results from phase 2 trials of DAC HYP were presented by Krzysztof Selmaj, MD, of the Medical University of Lodz (Poland) at a poster session on September 11, 2014 at the sixth triennial joint meeting of the Committee for Treatment and Research in Multiple Sclerosis of Europe and the Americas (ACTRIMS-ECTRIMS), held in Boston.

The randomized, double-blind, active-controlled DECIDE trial compared DAC HYP to interferon (IFN) beta-1a for the prevention of relapses; safety and tolerability were assessed as well. The study period ranged from 96 to 144 weeks, and patients were randomized 1:1 to DAC HYP 150 mg subcutaneous (SC) every four weeks or IFN beta-1a 30 mcg intramuscular (IM) once weekly.

The two arms of the study were almost exactly equal in size, with 919 and 922 patients in each, respectively. Demographic characteristics and disease states of the two groups were similar, and 41% of all patients had already received some form of disease-modifying treatment before enrollment in DECIDE.

In addition to adverse event (AE) monitoring, the battery of tests used to determine safety and tolerability included physical and neurological exams (to include vital signs and injection site monitoring), and laboratory studies, including hematology, blood chemistry, thyroid function, and urinalysis.

Although there was a similar rate of AEs in both treatment groups (91% in each) there were more serious AEs (SAEs) and also more discontinuations in the DAC HYP group compared with the IFN beta-1a group. Eighty-eight patients (10%) receiving IFN beta-1a vs. 141 patients (15%) receiving DAC HYP experienced SAEs, excluding MS relapse. AEs that led to treatment discontinuation (excluding MS relapse) occurred in 81 (9%) of the IFN beta-1a group compared with 130 (14%) in the DAC HYP group.

Of the commonly seen AEs in each treatment group (≥ 5%), investigators noted that nasopharyngitis, upper respiratory tract infections, influenza, oropharyngeal pain, rash, and lymphadenopathy were more common among patients receiving DAC HYP. In contrast, IFN beta-1a recipients experienced more MS relapses, influenza-like illnesses, hypotension, fever, and chills. Although infections occurred in 65% of the DAC HYP group and 57% of those receiving IFN beta-1a, no opportunistic infections were seen, and no patients developed progressive multifocal leukoencephalopathy (PML).

Cutaneous events, such as rash and eczema, occurred in 37% of the DAC-HYP group vs. 19% of those receiving IFN beta-1a; most events were mild or moderate. No Steven Johnson syndrome or topical epidermal necrolysis was seen.

Serious hepatic events occurred in less than 1% of both groups, though elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than five times the upper limit of normal was more common in the DAC HYP group (6% vs. 3%). Hematologic abnormalities were also rare and similar between groups. Two subjects receiving DAC-HYP had gastrointestinal SAEs that may have been immune-mediated; the drug was discontinued for both subjects, whose symptoms resolved. Malignancies occurred in less than 1% of each group, and there were no treatment related deaths in either group.

During the presentation, Selmaj referenced other work presented concurrently at this year’s ACTRIMS-ECTRIMS conference, as well as previously presented efficacy analyses, to conclude that DAC HYP may offer a treatment alternative to IFN beta-1a. This immune-modulating drug’s risk-benefit profile, he said, shows it has potential to be a valuable addition to the armamentarium against RRMS.