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FDA Updates - October 2016

In This Article

Adalimumab Biosimilar Approved to Treat Multiple Indications

On September 23, 2016, the FDA approved adalimu­mab-atto (Amjevita; Amgen), a biosimilar to adalimumab (Humira; AbbVie), to treat adults with: (1) moderate-to-severe active rheumatoid arthritis; (2) active psoriatic arthritis; (3) active ankylosing spondylitis; (4) moderate-to-severe active Crohn’s disease; (5) moderate-to-severe active ulcerative colitis; and (6) moderate to severe plaque psoriasis. The biosimilar is also indicated for the treatment of patients aged ≥4 years who have moderate-to-severe active polyarticular juvenile idiopathic arthritis.

“This is the fourth FDA-approved biosimilar. The biosimilar pathway is still a new frontier and one that we expect will enhance access to treatment for patients with serious medical conditions,” said Janet Woodcock, MD, Director, Center for Drug Evaluation and Research, FDA, Silver Spring, MD.

Administered as an injection, adalim­umab-atto was approved on the basis of evidence that included structural and functional characterization, animal study data, human pharmacokinetics and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and efficacy data demonstrating the drug’s biosimilarity to ada­limumab. Adalimumab-atto has been approved as a biosimilar, but is not an interchangeable agent.

Whereas the most serious known side effects of adalimumab-atto are infections and malignancies, injection-site reactions and infections are the most probable adverse reactions associated with its use.

Adalimumab-atto includes a boxed warning alerting healthcare professionals and patients to the increased risk for hospitalization and death, as well as to potentially fatal occurrences of lymphoma and other malignancies that have been reported in children and adolescents treated with tumor necrosis factor blockers, which include adalimumab products. A patient medication guide that includes important information about the uses and risks of the biosimilar must be dispensed along with adalimumab-atto.

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First Drug for Duchenne Muscular Dystrophy Granted Accelerated Approval

On September 19, 2016, the FDA granted eteplirsen (Exondys 51; Sarepta Therapeutics) accelerated approval for the treatment of patients with Duchenne muscular dystrophy who have a confirmed dystrophin gene mutation amenable to exon 51. This marks the first drug approval for patients with this condition.

“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” said Dr Woodcock. “Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”

Patients with Duchenne muscular dystrophy, a genetic condition that is rare and characterized by progressive muscle deterioration and weakness, often require the assistance of a wheelchair by their early teenage years, and gradually lose the ability to perform activities independently. The condition is caused by a deficiency of dystrophin, which is a protein that helps keep muscle cells together, and usually displays first symptoms in patients who are between the ages of 3 and 5 years.

Eteplirsen, which is administered via injection, received approval from the FDA under its accelerated approval pathway. This pathway arranges for promising drugs that treat serious or life-threatening conditions to reach patients earlier, all while the manufacturers continue to conduct trials to verify their drugs’ predicted clinical benefits.

The approval of eteplirsen was based on the surrogate end point of dystrophin increase observed in the skeletal muscle of certain patients treated with the drug. Although a clinical benefit (including improved motor function) has not been established for eteplirsen, the data submitted for its application demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with Duchenne muscular dystrophy who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, according to the FDA.

The most common side effects reported with the use of eteplirsen are balance disorder and vomiting.

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FDA Approves Etanercept Biosimilar for Multiple Indications

On August 30, 2016, etanercept-szzs (Erelzi; Sandoz) was approved by the FDA for the treatment of (1) patients with moderate-to-severe rheumatoid arthritis (as monotherapy or in combination with methotrexate); (2) patients with active psoriatic arthritis (including as combination therapy with methotrexate in those who do not respond adequately to methotrexate alone); (3) patients with moderate-to-severe polyarticular juvenile idiopathic arthritis (aged ≥2 years); (4) patients with chronic, moderate-to-severe plaque psoriasis who are contenders for systemic therapy or phototherapy (aged ≥18 years); and (5) patients with active ankylosing spondylitis.

Etanercept-szzs, which is administered via injection, is a biosimilar to etanercept (Enbrel; Amgen), which was originally licensed in 1998. Biosimilars can only be approved by the FDA if they demonstrate the strengths, mechanisms of action, routes of administration, and dosage forms of an already approved biologic agent. In terms of safety and efficacy, a biosimilar must not display clinically meaningful differences compared with the reference drug. Biosimilars must also be created in facilities that meet FDA standards.

“The biosimilar pathway is an important mechanism to improve access to treatment for patients with rheumatic and autoimmune diseases,” explained Dr Woodcock. “We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product.”

A review of evidence, including structural and functional characterization, and data pertaining to human pharmacokinetics, pharmacodynamics, clinical immunogenicity, animal studies, and clinical safety and effectiveness, demonstrating etanercept-szzs biosimilarity to etanercept, was the basis for the agency’s approval of the biosimilar.

Infections and injection-site reactions are among the most common side effects reported with the use of etanercept-szzs. Other possible side effects associated with the drug include neurologic events, congestive heart failure, and hematologic events.

This newly approved biosimilar includes a boxed warning alerting healthcare providers and patients to the increased risk for hospitalization- and death-inducing serious infections, including invasive fungal infections and tuberculosis. Lymphoma and other malignancies have also been reported in child and adolescent patients taking tumor necrosis factor blockers, which include etanercept products, and is also noted on the boxed warning. A patient medication guide that includes impor­tant information about the uses and risks of the biosimilar must be dispensed along with etanercept-szzs.

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