Case Date: 1/30/2008
Project Name: Health Care Project

On January 30, 2008, WLF issued a comprehensive report that concludes that FDA regulation of prescription drug promotion is being conducted in a manner that routinely violates both the First Amendment and FDA's statutory mandate. The report, part of WLF's "DDMAC Watch" program, is based on WLF's study of all regulatory compliance letters sent by FDA within the past year to pharmaceutical manufacturers. The report concludes that FDA routinely orders suppression of truthful speech, demands that manufacturers engage in "corrective advertising" in the absence of any evidence that consumers have been misled by supposedly misleading advertising, and violates federal administrative law by using compliance letters (rather than established notice-and-comment procedures) to adopt new agency policies regarding product promotion. WLF issued a similar report last year, covering the previous year's FDA compliance letters.

Case Date: 12/10/2007
Project Name: Health Care Project

On December 10, 2007, WLF called on DDMAC to withdraw a warning letter sent to GSK regarding GSK's allegedly improper promotion of Tykerb, a drug approved by FDA for treating breast cancer. DDMAC alleged that letters GSK sent to doctors regarding Tykerb were misleading because they omitted important risk information and overstated efficacy. WLF's letter to DDMAC alleged that DDMAC's action was inappropriate, because Tykerb's recognized risks were fully disclosed. DDMAC also faulted GSK's letters for overstating efficacy because they discussed an efficacy evaluation by the drug's IRC without fully disclosing efficacy data from a second, somewhat less favorable evaluation. WLF's response noted that the GSK letters explicitly disclosed that a second efficacy evaluation was less favorable. WLF said that, in light of GSK's disclosure, it is incumbent on DDMAC -- before charging that promotional material is misleading -- to develop some evidence that doctors have actually been misled.

Case Date: 11/15/2007
Project Name: Health Care Project

On November 15, 2007, WLF called on DDMAC to withdraw a letter sent to Scios Inc. regarding Scios's allegedly improper promotion of Natrecor. DDMAC alleged that a mouse pad and pen containing the Natrecor name improperly omitted risk information and did not qualify as "reminder labeling" (which is exempt from the risk-disclosure requirement). WLF responded that DDMAC failed to demonstrate that Scios had actually communicated any specific uses for Natrecor. The material included a picture of a seriously ill hospital patient partially submerged in water. DDMAC alleged that the picture conveyed to readers that Natrecor was indicated for treatment of congestive heart failure; it argued that because the mouse pad and pen disclosed Natrecor's approved use, Scios was required to list all risk information. WLF responded that DDMAC, before concluding that an ad conveys information about a drug's approved use, must gather some evidence to support that conclusion, such as consumer survey data.

Case Date: 10/16/2007
Project Name: Health Care Project

On October 16, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw an untitled letter sent to Eli Lilly and Co. on September 21, 2007 regarding Lilly's allegedly improper promotion of Cymbolta in a professional mailer. Cymbalta is a drug approved by FDA for treatment of a variety of conditions, including depression, anxiety disorder, and pain management. WLF's response took particular issue with DDMAC's assertion that the materials included an unsubstantiated claim. The claim in question -- that those treated with Cymbalta experience significantly less pain interference with overall functioning -- was based on several thorough studies conducted by Lilly. FDA was critical of the methodology of the studies. WLF responded that the First Amendment does not permit FDA to ban all discussion of the studies; at most, FDA can require Lilly to include additional disclaimers that point out potential shortcomings in the studies.

Case Date: 6/15/2007
Project Name: Health Care Project

On June 15, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a Warning Letter sent to Allergan, Inc. on May 25 regarding Allergan's allegedly improper promotion of Acular LS, an ophthalmic solution approved for treating ocular pain following corneal refractive surgery. DDMAC's letter to Allergan alleged that a professional journal advertisement for Acular LS misled readers by broadening the drug's indications beyond the indications approved by FDA and by including unsubstantiated superiority claims. WLF's response stated that a fair reading of the advertisement makes clear that Allergan was not claiming that Acular LS had been approved for uses other than those specifically approved by FDA. WLF also charged that DDMAC is violating Allergan's First Amendment rights by rejecting Allergan's right to present truthful information about its product so long as the information is accompanied by appropriate disclaimers.

Case Date: 6/11/2007
Project Name: Health Care Project

On June 11, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw an untitled letter sent to KV Pharmaceutical Co. on May 17, 2007 regarding KV's allegedly improper promotion of Clindesse in an e-Pharm/alert e-mail. Clindesse is a drug approved by FDA for treating bacterial vaginosis. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because it lacked any empirical basis for asserting that the email misled anyone. WLF also argued that the letter was improper in light of DDMAC's failure to provide any sort of guidance document on Internet and e-mail promotion, something that FDA has promised to provide since at least 1998. WLF also charged that DDMAC violated KV's First Amendment rights in attempting to prohibit KV from making any mention of clinical studies on the effectiveness of Clindesse.

Case Date: 6/11/2007
Project Name: Health Care Project

On June 11, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a Warning Letter sent to Enzon Pharmaceuticals, Inc. on May 21, 2007 regarding an Enzon flash card for Abelcet, a drug approved for treatment of invasive fungal infections. DDMAC stated that the flash card was misleading because it made unsubstantiated superiority claims and overstated the efficacy of Abelcet. WLF responded that DDMAC lacked any empirical basis for asserting that readers would think that Enzon was claiming that Abelcet is superior to competing products. WLF further argued that DDMAC violated Enzon's First Amendment rights in seeking to bar any discussion of in vitro data that support Enzon's efficacy claims. WLF argued that DDMAC is entitled to insist on disclaimers that note the shortcomings of in vitro data, but that it may not seek to bar all mention of the data.

Case Date: 5/21/2007
Project Name: Health Care Project

On May 21, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw untitled letters sent on May 7 to Schering Corp. and GlaxoSmithKline, regarding their allegedly improper promotion of Nasonex and Flonase. DDMAC alleged that professional detail aids for those drugs were false and misleading because they made unsubstantiated superiority claims as well as claims that the products are more effective than FDA believes has been demonstrated. WLF responded that both DDMAC letters were inappropriate, because they characterized promotional materials as misleading without a sufficient empirical basis and faulted references to legitimate studies. Nasonex and Flonase are drug approved by FDA for treating allergies. WLF letter to DDMAC charged that DDMAC violates the First Amendment where, as here, it seeks to prohibit a manufacturer from saying anything about the results of comparison studies without first considering whether any tendency to mislead could be avoided by affixing disclaimers.

Case Date: 5/1/2007
Project Name: Health Care Project

On May 1, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a Warning Letter sent to DUSA Pharmaceuticals, Inc. on April 20, 2007 regarding DUSA's advertisement for Levulan Kerastick, a drug approved for treatment of actinic keratosis ("AK," a type of precancerous lesion). DDMAC stated that the advertisement claimed that Levulan was superior to previously available products and was effective in treating all forms of AK. WLF responded that DDMAC lacked any empirical basis for asserting that readers would think that DUSA was claiming that Levulan had been approved for treating the most severe forms of AK. WLF also charged that DDMAC violates the First Amendment and administrative law when, as here, it seeks to prohibit a manufacturer from saying anything about the results of a study on patient preferences -- particularly in light of FDA's failure to release any guidance document setting forth standards for consumer preference surveys.

Case Date: 4/27/2007
Project Name: Health Care Project

On April 27, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a Warning Letter sent to Alcon Laboratories, Inc. on April 20, 2007 regarding Alcon's allegedly improper promotion of Ciprodex in a retail sales sheet and a sales aid. Ciprodex is a drug approved by FDA for treating certain infections. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because it lacked any empirical basis for asserting that readers of certain language in the sales aid would think that Alcon was claiming superiority, and that nothing in that language readily indicates that Alcon was making such a claim. WLF also responded that DDMAC acted improperly in faulting Alcon for citing a study that supported its "less severe pain" claim. WLF also noted that DDMAC was incorrect in asserting that Alcon failed to include all risk information; in fact, the sales sheet and sales aid contained the very information that the Warning Letter asserted was absent.

Case Date: 3/19/2007
Project Name: Health Care Project

On March 19, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw an untitled letter sent to Takeda Pharmaceuticals North America, Inc. on March 5, 2007 regarding Takeda's allegedly improper promotion of Rozerem in a direct-to-consumer television advertisement. Rozerem is a drug approved by FDA for treating insomnia. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because it lacked any empirical basis for asserting that readers of the ad would understand the ad to mean that Rozerem had been approved by FDA for use by children. The ten-second ad depicted a mother with school-age children and stated that it was "back to school season." WLF notted that the "reminder ad" said nothing about any of Rozerem's intended uses, and stated that it could easily be understood as suggesting that parents consider taking the drug. WLF noted that FDA had done no consumer testing regarding how viewers interpreted the ad.

Case Date: 3/19/2007
Project Name: Health Care Project

On March 19, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to Cephalon, Inc. on February 27, 2007 regarding Cephalon's allegedly improper promotion of Provigil. DDMAC alleged that a presentation for Provigil (handed out to Maryland health officials) was false and misleading because it failed to disclose all risk information and discussed off-label uses of the drug. WLF responded that to the extent that Cephalon could be deemed to have been supplying information regarding off-label uses of Provigil, the speech was constitutionally protected noncommercial speech; WLF noted that Cephalon was not attempting to sell any product to the Maryland officials and thus there can be little justification for FDA regulation of manufacturer speech in that context, in the absence of evidence from FDA that the speech was untruthful. WLF also called on DDMAC to develop a coherent policy regarding speech to State healthcare officials.

Case Date: 2/6/2007
Project Name: Health Care Project

On February 6, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw an untitled letter sent to MGI PHARMA, Inc. on January 28 regarding MGI's allegedly improper promotion of Gliadel Wafer, a drug approved for treatment of high-grade malignant gliomas after a tumor is removed. DDMAC alleged that a journal advertisement for Gliadel Wafer was false and misleading. WLF's response took particular issue with DDMAC's assertion that the ad included an unsubstantiated claim. The claim in question -- that Gliadel Wafer can begin working earlier than chemotherapy -- is substantiated by well-conducted animal studies. WLF argued that the First Amendment prohibits FDA from barring all mention of animal studies in ads for FDA-approved drugs, particularly where (as here) a disclaimer could eliminate any possibility that doctors reading the ad could be misled.

Case Date: 1/29/2007
Project Name: Health Care Project

On January 29, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw an untitled letter sent to WellSpring Pharmaceutical Corp. on December 19, 2006 regarding WellSpring's allegedly improper promotion of Dyrenium in a professional print advertisement. Dyrenium is a drug approved by FDA for treating edema in a variety of settings. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because it lacked any empirical basis for asserting that readers of the ad would think that WellSpring was making a claim that overstated Dyrenium's efficacy, and that nothing in the ad's language readily indicated that WellSpring was making such a claim. WLF also responded that DDMAC may not prohibit all references to clinical studies that conclude that the drug is superior to alternatives; if FDA does not like the study design, it should simply require the ad to mention any potential shortcomings in the study.

Case Date: 1/29/2007
Project Name: Health Care Project

On January 29, 2007, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to Daiichi Sankyo, Inc.(DSI) on January 12, 2007 regarding DSI's distribution of a promotional wall calendar for Evoxac, a drug used to treat symptoms of dry mouth in certain patients. DDMAC stated that the risks of taking the drug were inadequately displayed -- they were on the back of the calendar. WLF responded that DDMAC's "double disclosure" requirement (requiring that risk information be included both in the detailed "brief summary" portion of the promotional material and in the main body of the ad) is consistent neither with the First Amendment nor with federal statutes. WLF argued that it should be sufficient to reference in the main body of an ad a location to which readers can readily turn to find detailed risk information. WLF argued that requiring too much risk information on an advertisement tends to distract readers from the most important safety considerations for that drug.

Case Date: 11/15/2006
Project Name: Health Care Project

On November 15, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw warning letters sent to 3M Pharmaceuticals (on October 19) regarding 3M's allegedly improper promotion of Maxair Autohaler) and to Alcon Research Ltd. (on October 20) regarding Alcon's allegedly improper promotion of Nevanac. DDMAC alleged that a "flashcard" for Maxair and a sales aid for Nevanac were misleading because they failed to disclose all risk information and made unsubstantiated superiority claims. WLF's letter to DDMAC alleged that both of DDMAC's letters were inappropriate, because they characterized promotional materials as misleading without a sufficient empirical basis and inappropriately devalued animal studies relied on by the manufacturers. WLF charged that although DDMAC claimed that some readers might interpret the materials as making claims that the manufacturer has not substantiated, DDMAC provided no evidence that any consumers actually interpreted the materials in that manner.

Case Date: 11/6/2006
Project Name: Health Care Project

On November 6, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to Mallinckrodt, Inc. on October 13 regarding Mallinckrodt's allegedly improper promotion of Gastroview (a drug for use in connection with x-rays of the gastrointestinal tract) and OptiMARK (an injection for use with MRIs). DDMAC alleged that exhibit booth panels for the drugs were false and misleading because they failed to provide information regarding risks associated with use of the drugs. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because the exhibit booth panels clearly stated that company officials in the booth were available to provide full risk information. WLF argued that the availability of a company representative in the immediate vicinity provided adequate access to all risk information and ensured that no one would be misled regarding risks.

Case Date: 10/19/2006
Project Name: Health Care Project

On October 19, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to BioMarin Pharmaceuticals, Inc. on October 11 regarding BioMarin's allegedly improper promotion of Orapred. DDMAC alleged that a website for Orapred was misleading because it failed to disclose all risk information. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate, in large part because the website did, in fact, include all FDA-required risk information. DDMAC's only complaint was that BioMarin failed to include risk information on every page of the website. WLF's response also noted that DDMAC has never issued any specific guidance document on internet promotions of prescription drugs, despite many promises to do so and despite a 2001 WLF Citizen Petition pointing out the absence of such guidance. WLF argued that DDMAC should refrain from issuing any more warning letters regarding websites until after it provides appropriate guidance.

Case Date: 9/20/2006
Project Name: Health Care Project

On September 20, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to Reliant Pharmaceuticals, Inc. on September 14 regarding Reliant's allegedly improper promotion of Rythmol. DDMAC alleged that two promotional pieces for Rythmol were false and misleading because they failed to provide information regarding risks associated with use of Rythmol and improperly broadened the product's indicated uses. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate, in large part because Reliant's promotional material was not directed at anyone in a position to purchase Rythmol (i.e., patients or their doctors). Rather, the pieces were directed solely at pharmacists. WLF's response also noted that DDMAC was wrong in asserting that Reliant failed to disclose risk information; all the risk information cited by DDMAC was included in the FDA-approved prescribing information that accompanied the promotional materials.

Case Date: 9/13/2006
Project Name: Health Care Project

On September 13, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw a warning letter sent to Astellas Pharma US, Inc. on August 31 regarding Astellas's allegedly improper promotion of Prograf, a drug approved by FDA for combating organ rejection among patients receiving liver or kidney transplants. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate and violated the First Amendment because Astellas's claims were fully substantiated: they were based on a peer-reviewed study published in a leading medical journal. WLF said that DDMAC's actions were particularly ironic, given that FDA has actually accepted the study for inclusion in the approved product labeling for Prograf.

Case Date: 8/7/2006
Project Name: Health Care Project

On August 7, 2006, WLF issue a comprehensive report that concludes that FDA regulation of prescription drug promotion is being conducted in a manner that routinely violates both the First Amendment and FDA's statutory mandate. The report is based on WLF's study of all regulatory compliance letters sent by FDA within the past year to pharmaceutical manufacturers. The report concludes that FDA routinely orders suppression of truthful speech, demands that manufacturers engage in "corrective advertising" in the absence of any evidence that consumers have been misled by supposedly misleading advertising, and violates federal administrative law by using compliance letters (rather than established notice-and-comment procedures) to adopt new agency policies regarding product promotion. WLF has submitted its report to FDA in the form of a Citizen Petition, requesting that FDA take corrective action.

Case Date: 8/4/2006
Project Name: Health Care Project

On August 4, 2006, WLF wrote to DDMAC (FDA's Division of Drug Marketing, Advertising, and Communications),calling on DDMAC to withdraw an untitled letter sent to Eli Lilly and Co. on July 27 regarding Lilly's allegedly improper promotion of Alimta. DDMAC alleged that a patient brochure for Alimta was false and misleading because it did not include sufficient information regarding product risks and approved uses. WLF's letter to DDMAC alleged that DDMAC's actions were inappropriate because Lilly included detailed risk information in the prescribing information that accompanied the brochure; WLF said that there is no requirement that a manufacturer include risk information twice in its promotional material. WLF's response also took issue with DDMAC's conclusion that the brochure might mislead patients regarding Alimta's approved uses, given that the brochure made no claims regarding uses not approved by FDA and DDMAC collected no survey data indicating that any patients were misled.

Case Date: 7/6/2006
Project Name: Health Care Project

On July 6, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw warning letters sent to PrimaPharm, Inc. (on June 29) regarding PrimaPharm's allegedly improper promotion of Hydase and to GlaxoSmith Kline (on June 30) regarding GSK's allegedly improper promotion of Zovirax. DDMAC alleged that a sales aid for Hydase was misleading because it failed to disclose all risk information. DDMAC alleged that material regarding Zovirax on GSK's website was misleading because it overstated Zovirax's efficacy and omitted risk information. WLF's letter to DDMAC alleged that both DDMAC letters were inappropriate because they characterized promotional materials as misleading without a sufficient empirical basis and faulted GSK for citing clinical studies whose accuracy DDMAC has no basis for challenging. WLF charged that DDMAC sent its letters without even alleging that anyone was misled; rather, DDMAC is simply fearful that someone might be misled.

Case Date: 6/12/2006
Project Name: Health Care Project

On June 12, 2006, WLF wrote to OCBQ (FDA's Office of Compliance and Biologics Quality), urging it to withdraw an untitled letter sent to Wyeth Pharmaceuticals, Inc. on April 13, 2006 regarding Wyeth's allegedly improper promotion of ReFacto (a biological product approved by FDA to control bleeding and for use during surgery for patients suffering from hemophilia). WLF's letter to OCBQ argued that safety claims contained in a Wyeth consumer-directed brochure were consistent with ReFacto's FDA-approved labeling, that OCBQ had no basis for rejecting the studies upon which Wyeth based its safety claims, and that OCBQ had failed to provide any empirical basis for concluding that anyone was misled by Wyeth's brochure.

Case Date: 6/2/2006
Project Name: Health Care Project

On June 2, 2006, WLF wrote to DDMAC, calling on DDMAC to withdraw untitled letters sent to Sandoz, Inc. (on May 25) regarding Sandoz's allegedly improper promotion of bupropion) and to BIPI (on May 26) regarding BIPI's allegedly improper promotion of Spiriva Handihaler. DDMAC alleged that a professional print advertisement for bupropion was misleading because it failed to disclose all risk information. DDMAC alleged that a promotional labeling piece for Spiriva was misleading because it stated that another inhalant (Antrovent) was being discontinued in its CFC formulation without mentioning that Antrovent continued to be available in an HFA formulation. WLF's letter to DDMAC alleged that both DDMAC letters were inappropriate and violated the First Amendment because they characterized promotional materials as misleading without a sufficient empirical basis.