Seattle Genetics Inc. said Friday that its cancer drug Adcetris will carry a warning about a deadly type of brain infection that can occur in patients.
The company said Adcetris will carry a “black box” or boxed warning, the most serious type of warning label. The label will say that patients who take Adcetris can develop progressive multifocal leukoencephalopathy (PML), a rare brain infection. Seattle Genetics said two cases of PML have been reported in Adcetris patients, and a third is suspected.
Adcetris was approved in August 2011 for the treatment of Hodgkin Lymphoma (HL), a rare lymphoma known as systemic anaplastic large cell lymphoma. Adcetris is also an antibody-drug conjugate that combines an antibody and drug and enables the antibody to direct the drug to a target on lymphoma cells known as CD30. Since its approval, some 2,000 patients, worldwide, have received treatment with Adcetris. At that time of its approval, one case of PML was described in the label’s Warnings and Precautions section, the FDA said.
The signs and symptoms of PML may develop over several weeks or months and include mood changes; unusual behavior; confusion; thinking problems; loss of memory; changes in vision, speech, or walking; and decreased strength or weakness on one side of the body.
The company has said that the infection is quite rare disease of the central nervous system which either leads to the death of patient, or causes permanent disability. It does not affect the brain immediately but weakens it first, and then targets the immune system.
PML has also been noted with a number of drugs that impair certain aspects of immune function — most commonly with the multiple sclerosis drug natalizumab (Tysabri) but also with rituximab (Rituxan) and cladribine, among others. The condition results from reactivation of latent infection with the JC virus. It’s also a complication of AIDS and other immunodeficiency syndromes.
The FDA recommends that patients who develop any signs and symptoms of PML notify their healthcare professional immediately and that healthcare professionals should hold Adcetris dosing if PML is suspected, discontinuing Adcetris if a diagnosis of PML is confirmed. The agency also recommends that healthcare professionals refer to the current Adcetris drug label for the latest prescribing recommendations. Evaluation of PML may involve neurologist consultation, brain magnetic resonance imaging (MRI), and/or lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham virus (JC virus), and/or brain biopsy.
Also, a new contraindication warning against use of Adcetris with the cancer drug Bleomycin is being added to the drug label over an increased risk of pulmonary (lung) toxicity. The agency notes that patients receiving Adcetris in combination with bleomycin should speak with healthcare professional about stopping this combination of medications. Bleomycin, or Blenoxane, is used to treat cancers of the head, neck, and genitals.
By developing these agreed-upon label updates with the FDA,Seattle Genetics’ medical officer Thomas Reynolds said “we aim to heighten awareness among healthcare professionals”. He added that although PML in lymphoma patients “can be caused by factors such as underlying disease and prior therapies that affect the immune system, a contributory role of Adcetris cannot be excluded”.
Seattle Genetics markets Adcetris drug in the U.S. and Canada while Takeda Pharmaceutical Co. markets it elsewhere.