Biogen Idec, Inc announced the FDA approval of Plegridy (peginterferon beta-1a), a new treatment for relapsing-remitting multiple sclerosis (RRMS).1 Plegridy is currently the only pegylated beta interferon approved for use in RRMS. The recommended dosing is a subcutaneous injection to be taken once every two weeks and it can be administered via an autoinjector or a prefilled syringe.
The approval of Plegridy is exciting in that it is an innovative addition to the interferon class of MS treatments, whose safety and efficacy are well established. Plegridy is a pegylated version of Biogen Idec’s Avonex (intramuscular interferon beta-1a), with a more convenient dosing regimen.
Pegylation is a process by which polyethylene glycol chains are attached to protein and peptide drugs.2,3 This process prolongs the circulation time of the molecule in the body by increasing its size, enabling a longer half-life and stabilizing the molecule by improving its solubility and shielding the molecule from proteolytic enzymes. Pegylation is a well-established scientific process; several pegylated therapeutics are currently available, all of which have at least comparable efficacy, safety and tolerability to their unmodified forms.3
The approval of Plegridy was based on results from the pivotal ADVANCE trial, which included over 1500 patients with RRMS. ADVANCE was a 2-year, double-blind, parallel group, phase 3 study, with a placebo-controlled design for the first 48 weeks.1,4 Patients with RRMS who were between 18 and 65 years of age, with EDSS score ≤5 were randomly assigned to placebo or Plegridy once every 2 weeks or every 4 weeks. The primary study endpoint was annualized relapse rate at 48 weeks. In the first year of the study, Plegridy dosed once every two weeks significantly reduced ARR by 36% versus placebo (P=0.0007). Additionally, when compared with placebo, Plegridy reduced: the risk of 12-week confirmed disability progression by 38% (P=0.0383), the number of new gadolinium-enhancing lesions by 86% (P<0.0001) and new or newly enlarging T2-hyperintense lesions by 67% (P<0.0001).
In the placebo-controlled phase (year 1) of the study, the most common adverse drug reactions for Plegridy dosed every 14 days were injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia.1,4 Each occurred in more than 10% and at least 2% more than placebo. The most commonly reported adverse event leading to discontinuation in study participation for patients treated with Plegridy every 14 days was influenza-like illness.
The Prescribing Information for Plegridy includes the following warnings and precautions:
Hepatic injury: monitor liver function tests; monitor for signs and symptoms of hepatic injury; consider discontinuation of PLEGRIDY if hepatic injury occurs.
Depression and suicide: patients should report immediately any symptom of depression or suicidal ideation to their healthcare provider; consider discontinuation of PLEGRIDY if depression occurs.
Seizure: Seizures are associated with the use of interferon beta. Exercise caution when administering PLEGRIDY to patients with a seizure disorder.
Anaphylaxis and other allergic reactions: serious allergic reactions have been reported as a rare complication of treatment with interferon beta. Discontinue PLEGRIDY if a serious allergic reaction occurs.
Injection site reactions: change injection site or consider discontinuation of PLEGRIDY if there is necrosis.
Congestive heart failure: patients with pre-existing significant cardiac disease for worsening of cardiac symptoms should be monitored.
Autoimmune disorders: consider discontinuation of PLEGRIDY if a new autoimmune disorder occurs.
The approval of Plegridy adds another treatment option to the MS treatment armamentarium.
Biogen Idec’s PLEGRIDY™(Peginterferon Beta-1a) Approved in the US for the Treatment of Multiple Sclerosis. Market Watch. Aug 15, 2014. http://www.marketwatch.com/story/biogen-idecs-plegridypeginterferon-beta-1a-approved-in-the-us-for-the-treatment-of-multiple-sclerosis-2014-08-15-181594426. Accessed August 16, 2014.
Plegridy prescribing information. August 2014. http://www.plegridy.com/pdfs/plegridy-prescribing-information.pdf. Accessed August 16, 2014.
Kieseier BC1, Calabresi PA. PEGylation of interferon-β-1a: a promising strategy in multiple sclerosis. CNS Drugs. 2012;26(3):205-214.
Calabresi PA, Kieseier BC, Arnold DL, et al. Pegylated interferon β-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014;13(7):657-665.