Feb. 4, 2014 — Many of the 14 enforcement letters issued by the FDA’s Office of Prescription Drug Promotion (OPDP) cited similar allegations it has cited in the past, including omission of risk information, unsupported superiority claims and overstatement of efficacy, according to OPDP officials who responded Jan. 30 to questions about the three Warning Letters and 11 Untitled Letters it issued from July to December 2013.
The first question and a subsequent question asked during the FDA Enforcement Update requested whether OPDP staff target boxed warning drugs or orphan drugs, because those types of products were represented in the most recent batch of enforcement letters.
OPDP Regulatory Counsel Robyn Tyler explained that OPDP “does not specifically target boxed warning drugs, but we do have limited resources, and generally use a risk-based approach to identify matters to pursue for enforcement.” OPDP Regulatory Counsel Julie Chronis echoed this position when asked about orphan drug enforcement. “We do not target specific designations,” Chronis said.
Other audience questions focused on letters alleging omission of risk information. One caller wondered why the Untitled Letter sent Dec. 20, 2013, to DaraBiosciences Inc. for SOLTAMOX had not been a Warning Letter, because it raised an omission of risk objection. “An omission of risk objection is not dispositive of whether a letter should be a Warning Letter or not,” said OPDP Regulatory Counsel Cynthia Ng. She listed the following as factors that would lead to the issuance of a Warning Letter over an Untitled Letter:
- Nature or egregiousness of the violation;
- Magnitude of impact on the public health;
- Need for corrective action; and
- Repetitive behavior.
Indeed, Tyler explained that a Warning Letter was sent July 25, 2013, to Acorda Therapeutics Inc. for serious risk omission for AMPYRA because the agency had sent an Untitled Letter to the company – for false or misleading promotional materials by Acorda – as recently as June 21, 2012. A Warning Letter sent Nov. 18, 2013, to Kadmon Pharmaceuticals LLC for RIBASPHERE RIBA PAK cited omission of risk information and the fact that OPDP raised “similar violative promotional activities” in a March 21, 2011, Untitled Letter.
In a Dec. 9, 2013, Untitled Letter to Covis Pharmaceuticals for LANOXIN tablets, OPDP cited the company for failure to disclose serious risks while promoting efficacy claims in a two-page physician letter. The letter “failed to disclose many serious risks and completely omitted the contraindication as well as other warnings and precautions while prominently featuring efficacy claims,” Tyler stated. She added that although some risk information was included in the letter, that information was listed after the signature block and on the back of the letter. “Risk information needs to be of a comparable prominence and readability as efficacy information,” she said.
Superiority claims issues also were raised. A caller asked Chronis why comparisons to an active control in a clinical trial were not sufficient to support claims, as noted in a Nov. 5, 2013, Untitled Letter to Sunovion Pharmaceuticals Inc., regarding its BROVANA inhalation solution. “Broad claims that Brovana was clinically superior over other COPD therapies need to be supported by adequately controlled, head-to-head studies demonstrating that Brovana is clinically superior,” Chronis explained. The clinical trials used by Sunovion to support the claims “were not designed to measure clinical superiority.”
On question that went unanswered by OPDP officials during the session focused on the Nov. 18, 2013, Warning Letter sent to Aegerion Pharmaceuticals Inc. citing statements made about JUXTAPID by the company CEO during an interview on the CNBC show, “Fast Money.” The questioner asked why a show targeted toward investors was cited in a Warning Letter. (For related story, see http://www.cohealthcom.org/?p=2054)
After a brief silence, session moderator OPDP Senior Lead Regulatory Counsel Bryant Godfrey responded, “We are going to have to come back to that question.” However, although there were more than 10 minutes left in the designated period for the enforcement update, the session was concluded without an OPDP response to the query.