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FDA Failures Result in Wider Approval of Orphan Medication for Sleep Disorder

June 11, 2015

FDA Failures Result in Wider Approval of Orphan Medication for Sleep Disorder

Rather Than Correct Labeling Error, FDA Retroactively Issued a Second Approval Letter Changing the Approved Use

WASHINGTON, D.C. – An apparent and troubling mistake by the U.S. Food and Drug Administration (FDA) expanded the use of a sleep disorder medication beyond the narrow patient group for which it was originally approved and should be immediately corrected, Public Citizen said in a petition today.

In 2013, Vanda Pharmaceuticals sought FDA approval for tasimelteon (Hetlioz) as an orphan drug, which is a medication for a very specific group of patients who have a rare medical condition. Under the orphan medication approval process, fewer clinical trial data are required than for other medications.

Consistent with the orphan status granted by the FDA, Vanda Pharmaceuticals requested approval of tasimelteon specifically for treatment of individuals with the rare sleep disorder known as “non-24” sleep-wake disorder – and who were totally blind, with no perception of light. The relevant clinical trials were conducted only in such individuals. Non-24 hour sleep-wake disorder is a chronic sleep disorder that occurs when individuals are unable to synchronize their internal body clock to the 24-hour light-dark cycle.

At least 26 FDA review documents signed by 42 agency officials prior to tasimelteon’s approval explicitly stated that Vanda Pharmaceuticals was seeking approval for use in totally blind patients (one document related to the review of the product labeling signed by two officials was the exception). According to the original approval letter issued on Jan. 31, 2014, the FDA approved tasimelteon for treatment of “Non-24-hour sleep-wake disorder in blind patients without light perception.” That same day, the agency issued a press release announcing the medication’s approval to “treat non-24-hour sleep-wake disorder (‘non-24’) in totally blind individuals.”

But because of an apparent major oversight by the FDA, the description of tasimelteon’s approved use in the product label did not match the one found in the original approval letter, omitting the phrase “in blind patients without light perception.” The label therefore effectively expanded tasimelteon’s approval to anyone diagnosed with non-24 sleep-wake disorder – widening the pool of potential users beyond patients who are totally blind.

At some unknown time after the initial approval, the FDA realized it had made a mistake. However, rather than take appropriate action by simply correcting the label, the FDA compounded its original mistake by issuing a second approval letter that stated the original approval letter contained an error in the description of tasimelteon’s approved use. The second letter modified the description of the medication’s approved use to match the one found in the erroneous label.

Confusion reigns as to when the FDA issued the second approval letter. While the wording of the second letter clearly implies that it was issued some time after tasimelteon’s approval, the FDA dated the letter Jan. 31, 2014 – the same day the original approval letter was issued.

“The FDA has violated the legal standard required for drug approval. The FDA’s actions in response to the original mistake in approving tasimelteon’s erroneous label are unacceptable and deeply disturbing,” said Dr. Michael Carome, director of Public Citizen’s Health Research Group. “Because of its failures in this matter, the FDA has allowed a potentially dangerous medication to be given to people for whom there is a lack of substantial evidence that it is safe and effective. It is time the FDA fixes the errors and explains its actions surrounding this approval.”

Today, Public Citizen is submitting a public records request seeking all documents related to the FDA’s actions in this matter, including all documentation of pertinent communications with Vanda.

In addition to its errors over the approved use of tasimelteon, the FDA omitted from the label some evidence of harmful effects, including carcinogenic and reproductive toxicity findings, seen in the animal studies conducted before approval. An FDA pharmacology reviewer noted these findings, but felt that, because tasimelteon was to be targeted to the limited population of totally blind patients, the toxicities would not preclude approval as long as they were “fully disclosed in the label,” which they were not. Notably, the FDA reviewer’s recommended language for the label was almost completely redacted in the publicly released review for tasimelteon.

In its petition, Public Citizen is urging the FDA to immediately correct the description of the approved use on the tasimelteon label to limit it to totally blind patients suffering from non-24 sleep-wake disorder, and then inform both patients and doctors of the change. The petition also asks that the warning label include the acknowledged toxic effects seen in the animal studies that were omitted from the label and that a large, post-marketing clinical trial be conducted to obtain more information on the risks associated with tasimelteon.

View the petition.