FDA expert panel supports Enbrel option for children with serious psoriasis
A panel of outside experts convened by the U.S. Food and Drug Administration (FDA) has recommended that the biologic Enbrel be approved for use in children with moderate to severe plaque psoriasis. As the Associated Press reported:
The Food and Drug Administration's panel of dermatology experts narrowly voted 7-5 that the drug's benefits outweigh its risks, with one abstention, according to an agency spokeswoman. Panelists said they would prefer the drug only be approved for severe cases of the disease, due to potentially dangerous side effects, including cancer.
... The agency often follows the advice of its panels, though it is not required to do so.
Enbrel is already approved to treat psoriasis [and psoriatic arthritis] and rheumatoid arthritis in adults, and juvenile arthritis in children.
Earlier this month, the FDA announced it was investigating whether Enbrel and similar drugs - including Johnson & Johnson's Remicade and Abbott Laboratories' Humira - increase the risk of cancer in children.
FDA uncovered nine reports of malignant cancers in children as part of its safety review of Enbrel, which was released ahead of Wednesday's meeting.
Michael Paranzino, president of Psoriasis Cure Now, appeared before the Committee and spoke about the devastating nature of serious psoriasis in children and the difficult challenges parents face in finding appropriate treatments for them, as no systemic, or internally administered, treatments are currently approved for use in children. (Most children with moderate to severe psoriasis are treated with psoriasis medications that have been tested on and approved for use by adults. Such “off-label” use is legal but adds to parents’ concerns, as data is lacking about the treatments’ safety in children.)
As Bloomberg News reported:
Amgen Inc.'s anti-inflammatory drug Enbrel could help hundreds of children battling severe psoriasis, a patient advocacy group told U.S. regulators considering whether to extend the medicine's use.
... An FDA staff report released Monday questioned whether the drug's benefits for children outweigh its risks, including an increased chance of serious infections and cancer. If approved, Amgen said it would market the drug for use in about 1,500 children with particularly bad cases of psoriasis. Psoriasis patients told the panel that families want the option.
"Which black box do you want to subject your child to, which tough choice?" said Michael Paranzino, 42, president of Psoriasis Cure Now, a Kensington, Maryland advocacy group. "As opposed to the committee making that decision for every child in America, I think we have to empower the physicians and parents across the country to make that call."
Amgen, based in Thousand Oaks, California, has given grants to Psoriasis Cure Now, as have rival drug companies, said Paranzino, who said he and two of his nieces have psoriasis.
The NY Times has a good summary of the current FDA scrutiny of pediatric use of several biologics being used to treat psoriasis and other serious diseases:
The Food and Drug Administration said Wednesday that it was investigating whether four drugs used to treat rheumatoid arthritis and other immune system diseases might increase the risk of cancer in children.
The F.D.A. said that it had received reports of 30 cases of cancer over 10 years among children and young adults treated with those drugs, which are sold by Amgen, Abbott Laboratories and other companies.
But the agency did not make clear how many children had taken the drugs or whether the cancer incidence among them was higher than would be expected. And it said that for now, it believed that the potential benefits of the medicines outweighed the potential risks "in certain children and young adults."
The drugs involved are Enbrel, sold by Amgen and Wyeth; Remicade, sold by Johnson & Johnson and, in Europe, by Schering-Plough; Humira, sold by Abbott Laboratories; and Cimzia, which won approval in April and is sold by UCB, a Belgian company. [Cimzia is approved for Crohn’s disease but not approved for psoriasis or psoriatic arthritis; the others are approved for both psoriasis and psoriatic arthritis.]
All the drugs try to damp inflammation by blocking a protein called tumor necrosis factor, and they are used to treat various immune diseases including rheumatoid arthritis, psoriasis and Crohn’s disease, which is an inflammation of the bowel.
The TNF-blockers, as they are known, represent one of the most successful classes of drugs ever developed using biotechnology. Remicade, Humira and Enbrel had combined sales of more than $13 billion last year.
But use in children constitutes a small part of the total. Dr. Michael Severino, an Amgen executive, said about a half-million patients had been treated with Enbrel since its approval about a decade ago, of which only 12,000 were children.
... Since the drugs block part of the immune system, it has always been known that they might contribute to higher risk of cancers and also infections. The labels for the drugs all contain warnings to that effect — particularly about the risk of lymphomas, which are cancers of immune system cells.
About half the cancers reported in the children getting the drugs were lymphomas, including Hodgkin’s disease and non-Hodgkin’s lymphoma, the F.D.A. said.
A study that pooled data from randomized clinical trials, found that adults given Humira or Remicade to treat rheumatoid arthritis had 2.4 times the cancer rate of those in the control groups. "It's clearly something we have to be concerned about and discuss with our patients," said Dr. Eric L. Matteson, chairman of rheumatology at the Mayo Clinic and an author of the study, which was published in The Journal of the American Medical Association. Dr. Matteson has been a consultant to many of the companies developing such drugs.
Dr. Edward H. Giannini, professor of pediatric rheumatology at the University of Cincinnati, said that 70,000 to 100,000 children in the United States had juvenile idiopathic arthritis, and that the biotech drugs were "unequaled" in their ability to control the disease. "This was a disease that put kids in wheelchairs," he said.
Dr. Giannini, who received consulting fees from the companies for helping to devise their pediatric clinical trials, said that no cases of cancer were seen in the clinical trials that led to Enbrel’s approval for pediatric use. And a subsequent registry that followed 600 children found no cases after more than 800 patient-years of exposure.
Still, he said, "We have to be careful with the safety aspects of giving immune response modifiers to very young children," whose immune systems might not be mature yet.
Michael Parks, a spokesman for Johnson & Johnson, said the company had already submitted data to the F.D.A. Most of the cancer cases associated with Remicade use were in children with Crohn’s disease or ulcerative colitis. And all but one of those children also received other immune-suppressing drugs with a known cancer risk, he said.
Laureen Cassidy, a spokeswoman for Abbott, said there had been no instances of cancer in children given Humira in clinical trials or in postapproval safety studies. Humira was approved for pediatric use a few months ago.
There are some children who desperately need access to these advanced therapies; for most other children with psoriasis, fortunately, it can be avoided. The approval of Enbrel for pediatric use (4-17 is the age span recommended by the Committee) would help children with serious psoriasis. But certainly, parents must closely investigate with their child’s physician the known and potential risks and weigh them against the benefits of these treatments. And it is imperative that the companies that market these therapies continue to investigate the long-term risks of these treatments and publish their findings.
[More resources for children with psoriasis: www.PsoriasisKids.org .]