For regular watchers of the US Food and Drug Administration's (FDA) so-called "untitled letters"-letters sent to companies alleging failure to adhere closely enough to federal advertising regulations-it's been a slow few months.
Between 5 February 2013 and 31 July 2013, FDA sent 13 untitled letters to members of industry, detailing unfairly balanced claims, missing safety warnings, over-stated efficacy and even the aesthetic balance of the advertising and promotional pieces.
But after FDA posted the last of those letters to its website on 5 September 2013 (there's often a lag between when a letter is sent and made public), its untitled letters webpage fell quiet. From 6 September through 28 October 2013, the agency posted no new letters, perhaps owing to the difficulties associated with keeping its doors open during the 1-16 October government shutdown.
Sunovion Breaks the OPDP Dry Spell
But at long last FDA's Office of Prescription Drug Promotion (OPDP) has posted a new untitled letter, this one to Sunovion Pharmaceuticals regarding its chronic obstructive pulmonary disease (COPD) inhaler Brovana (arformoterol tartrate). The inhaled solution was approved in October 2006 under New Drug Approval (NDA) #021912.
While COPD is a lung condition that effects the full utilization of the airway, Brovana's labeling clarifies that the drug is not intended for use in asthmatics, as its use for that condition has not yet been established. The drug is also associated with some serious safety risks, including asthma-related death, for which it has a prominent black box warning on its label. Other risks include the deterioration of disease, acute COPD episodes, and reactions in those prone to hypersensitivity to some of Brovana's core ingredients.
FDA's untitled letter cites three major issues with a promotional brochure published by Sunovion: overstated efficacy, unsubstantiated claims and minimized risk information.
To the former, FDA contends that the drug's taglines, "Get back into daily living" and "With the right COPD medicine, you may get back to daily living," serve to overstate the efficacy of the drug by implying that taking the drug will allow patients to "resume their baseline activities of daily living." Studies in support of the drug showed a far more modest improvement in lung function of just 11% over baseline (as measured by forced expiratory volume in one second, or FEV1).
FDA's letter also calls attention to "unsubstantiated claims" in the company's brochure. FDA cited a set of questions asked of patients in the brochure, which asked them if they used a nebulizer more than four times a day, if they had difficulty using their inhalers, or if their current treatment felt unsatisfactory.
The questions had the net effect of implying that Brovana was clinically superior to other medications, including those that did not experience success with other medications, FDA said. While several studies backed up Sunovion's claims to these points, FDA said none had been specifically assess its benefits relative to comparator drugs like salmeterol. Accordingly, FDA concluded that the studies do not constitute "substantial evidence."
Finally, FDA pointed to an unbalanced treatment of risk information relative to the drug's benefits.
"The patient brochures prominently present efficacy claims in large, bolded font size and colorful text and graphics surrounded by a significant amount of white space" FDA observed. "In contrast, risk information is presented in small font, surrounded by little white space, and in single-spaced format."
FDA asked that Sunovion immediately cease use of the brochures and submit a written response to the agency. The company's website for Brovana has since been taken down and replaced with a link to the company's FDA-approved prescribing information. A cached version of the website contained a different tagline for the drug, "add better breathing to your daily routine."
OPDP Letter to Sunovion
Brochure Cited by OPDP