With Forest Laboratories' chairman and CEO facing exclusion from government health care programs stemming from the firm's guilty plea on off-label promotion charges, the last thing the company needs is a notice of violation letter from FDA due to alleged off-label promotion by a sales representative.

Duncan-Williams analyst Irina Rivkind pointed out in a May 3 note to investors that the violation cited in the letter, which involved the fibromyalgia drug Savella (milnacipran), is said to have occurred May 12, 2010, before last September, when the company signed a corporate integrity agreement with the federal government "and may therefore be exempt" (Also see "Forest Admits To Knowingly Obstructing FDA Inspection In Guilty Pleas On Levothroid, Celexa Marketing" - Pink Sheet, 15 September, 2010.).

Nevertheless, the April 28 letter from the Division of Drug Marketing, Advertising and Communications points to another apparent instance of a troubling pattern of the same behavior that led the company to agree to a $313 million settlement with the Department of Justice. Forest said in an email that its "policy prohibits off-label promotion and we take any allegations of non-compliance very seriously."

According to DDMAC, the sales representative stated that Savella, a selective serotonin norepinephrine dual reuptake inhibitor, "is useful in back pain and mood disorder, because it concurrently elevates mood and relieves depression... [and] that Savella is approved for depression in Europe." The salesperson said this without the physician having requested the information, FDA added. Thus, the drug was "misbranded," or promoted off label.

Complaints about verbal statements like these are held to a high standard of proof, according to DDMAC's Michael Sauers, group leader in Direct-to-Consumer Review Group I. The complainant would be required to submit an affidavit about the exact content of the sales rep's statement, he said (see Also see "DDMAC's "Bad Ad" Enforcement Often Requires Affidavits" - Pink Sheet, 4 May, 2011. ).

Water Under The Bridge?

The company could take comfort in Rivkind's analysis, which was that "we believe this is an isolated incident and expect the company to quickly address it and therefore avoid any significant penalties under the [corporate integrity agreement]. ...Some minor fines are possible."

However, the investment banking firm added, "What is less clear is whether the ... letter would aid the government's recent attempt to exclude [Chairman and CEO] Howard Solomon from participation in federal health care programs" (Also see "How Broadly Will OIG Enforce Its Exclusion Powers? Possible Action Against Forest CEO Offers A Lesson" - Pink Sheet, 14 April, 2011.).

Sales of Savella for the year ending March 31 were $90.2 million.

Better Than Cymbalta?

According to FDA's letter, the sales representative also said that Savella has a three-to-one affinity for norepinephrine reuptake inhibition, making it "a better analgesic than [Lilly's] Cymbalta [duloxteine]." While the first part of this claim is true, the second part "is misleading because it implies that Savella is clinically superior (i.e., more effective) to Cymbalta because of its increased affinity for norepinephrine reuptake inhibition in vitro."

"Pre-clinical in vitro data demonstrating Savella's increased affinity for norepinephrine reuptake inhibition does not constitute substantial evidence to support claims implying that Savella is more effective than Cymbalta," FDA said.

Unjustified elevation of in vitro data to the level of clinical data for promotional purposes has been a theme for DDMAC recently, for example in an April 19, 2010 warning letter to GlaxoSmithKline over a letter-sized catalog promoting the topical antibiotic Altabax (retapamulin ointment, 1%) to health care professionals (Also see "Antibiotic Promotions Can't Rely On In Vitro Claims, Even If Labeling Might" - Pink Sheet, 10 May, 2010.).

The NOV letter to Forest adds that the sales representative claimed Savella is less sedating than Lyrica (pregabalin) and does not result in peripheral edema and/or as much weight gain as the Pfizer drug does, a claim that is not justified by head-to-head trials. This also implied unjustifiably that Savella is safer than Lyrica, and on top of that the sales rep did not mention the former drug's risks and made an unsubstantiated claim about its mechanism of action.

Forest said, "We were not previously aware of this allegation and an investigation into this allegation is currently underway. Forest has a very strong training and compliance program, including a number of mechanisms to monitor the activities of our sales force. If there was a violation of our policies, we will take appropriate action."

Also see "How Broadly Will OIG Enforce Its Exclusion Powers? Possible Action Against Forest CEO Offers A Lesson" - Pink Sheet, 14 April, 2011.- Martin Berman-Gorvine ( m.berman-gorvine@elsevier.com )

Could Forest's DDMAC Letter For Off-Label Promotion Doom CEO Solomon?

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