DID - Oct. 7, 2009 - Issue

Vol. 8 No. 195

Industry Asks FDA for Internet-Specific Advertising Guidance

Drug and biologics makers that advertise products online have asked the FDA to give more specific recommendations on issues such as presenting risk information through hyperlinks in its final guidance on including drug risks in promotional materials.

A draft guidance released in May says that drugmakers should focus on the overall impression their advertising conveys to healthcare professionals and consumers to determine whether each piece of promotional material complies with the law and FDA regulations (DID, May 27). The comment period closed Aug. 25. FDA spokeswoman Karen Mahoney could not estimate when the final guidance might be out, telling DID, “We are in the process of reviewing and considering the comments received to the draft guidance.”

The issue was pushed into the spotlight last month, when the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) Director Thomas Abrams said the division had focused on sponsored links on internet search engines this year, issuing 14 warning and untitled letters for such promotions out of a total of 33 warning and untitled letters for direct-to-consumer advertising from Jan. 1 through Sept. 15. The emphasis on sponsored links is a “very resource-intensive area,” Abrams said (DID, Sept. 22).

PhRMA criticizes the agency’s draft guidance and recent letters to advertisers from DDMAC, in comments posted on the draft. “These letters have applied ‘traditional’ interpretations of rules regarding drug advertising and promotion without apparent consideration of the fact that internet promotion can be fundamentally different from print and broadcast promotion,” PhRMA says.

The organization adds that the agency “should acknowledge that search engine users generally enter queries into search engines with the expectation and intent that they will be directed to, and will view, a page to which the sponsored search result hyperlinks. In addition, promotional web sites are typically linked together to form what may be interpreted as a collective promotional piece.”

Similarly, the Biotechnology Industry Organization critiques the draft because it “does not distinguish between online advertisements versus traditional promotional methods [and] does not address the unique and distinctive issues raised by internet promotion. … For example, the guidance does not address whether companies can use hyperlinks to appropriately communicate important risk information, especially if the hyperlink is clearly displayed.”

PhRMA also notes that the agency does not say in the draft whether it will consider the placement of the risk information in an online promotion and its proximity to the relevant claim, the inclusion and relative prominence of clearly labeled hyperlinked disclosures, whether items in other parts of the piece distract from the risk information, how long a promotional piece would have to be to necessitate repeating the risk information, and whether the language of the disclosure is understandable to the intended audience.

The organization adds that “not all activities regarding prescription medicines on the Internet are promotional, and not all websites maintained by or on behalf of a manufacturer qualify as promotional labeling or advertising within the meaning” of the Food, Drug and Cosmetic Act.

Earlier this year, Arnold Friede, former senior corporate counsel for Pfizer and counsel to law firm McDermott Will & Emery, told DID that DDMAC has been asserting that sponsored links connecting internet users to a brand drug web page should be evaluated separately as advertisements — and that the information on the product’s website is not taken into account when determining whether a sponsored link is misleading, a view he thinks is mistaken (DID, April 9).

Mahoney said the FDA will address such criticisms at a hearing Nov. 12 to 13 on promotion of FDA-regulated medical products using the internet and social media tools.

The draft “Guidance for Industry: Presenting Risk Information in Prescription Drug and Medical Device Promotion” can be viewed at www.fdanews.com/ext/files/FDA-2008-D-0253-0001.pdf. PhRMA’s comments can be seen at www.fdanews.com/ext/files/FDA-2008-D-0253-0018.1.pdf.  — Martin Berman-Gorvine


EC Staff Visit Drugmakers as Part of Larger Probe

The European Commission (EC) conducted surprise inspections of Teva Pharmaceutical Industries, Sandoz and other drugmakers in a continuing investigation of alleged anti-competitive practices to delay generic-drug competition.

The inspections are a preliminary step in the investigation of suspected anti-competitive practices, but they don’t imply the companies have engaged in such behavior, the EC says in an Oct. 6 statement about the raids.

Denise Bradley, a spokeswoman for Teva Pharmaceuticals USA, confirmed that EC officials visited the company’s Paris offices. Sandoz said the commission had stopped at its Sandoz France offices and wouldn’t comment on the nature of the investigation.

The EC began an inquiry last year into competition in the drug industry that included surprise inspections of company offices (DID, Jan. 17, 2008 ). The purpose of the inquiry is to uncover the reasons for a decrease in the number of novel medicines reaching the market and why generic drugs are being delayed from entering the market.

The inspections come roughly a week after Neelie Kroes, the European Commissioner for Competition, told the European Parliament that the probe is expanding to include new cases (DID, Sept. 30 ).

The EC opened a formal antitrust investigation in July against French drugmaker Les Laboratoires Servier for suspected breaches of the commission’s rules on restrictive business practices. In particular, the EC said it is investigating whether business agreements between the company and several generic-drug makers, including Teva, may have hindered the introduction of a generic version of the company’s cardiovascular drug Coveram (perindopril arginine/amlodipine besylate).

Sanofi-Aventis didn’t return calls confirming whether they were part of the probe by press time. — Elizabeth Jones


Supreme Court Rebuffs Mylan in Attorneys’ Fees Dispute

The U.S. Supreme Court has refused to hear a case brought by Mylan Laboratories and Alphapharm involving attorneys’ fees awarded to Takeda Chemical Industries as a result of the decision in a patent dispute over Takeda’s diabetes drug Actos.

The Supreme Court did not comment on its refusal to hear Mylan and Alphapharm’s appeal of a district court ruling requiring them to pay Takeda’s fees after they failed to prove a patent covering Actos (pioglitazone HCl) was invalid, according to the court’s website.

Takeda won its patent case against the two generic companies in the U.S. District Court for the Southern District of New York in February 2006 (DID, Feb. 23, 2006 ). The District Court ruled that Takeda’s ’777 patent for the active ingredient in Actos is valid and enforceable. As a result of the ruling, Alphapharm and Mylan cannot sell generic versions of Actos until Takeda’s patent expires in 2011.

The court also granted Takeda’s request to award it attorneys’ fees and ordered Alphapharm to pay $5.4 million and Mylan $11.4 million, according to court documents. The generic companies appealed the fees, calling them excessive, to the U.S. Court of Appeals for the Federal Circuit.

However, the Appeals Court found their arguments in the case Takeda Chemical Industries, Ltd., et al. v. Mylan Laboratories, Inc., et al. to be “unpersuasive.” — Elizabeth Jones


OncoGenex Drug Gets Additional Fast-Track Designation

OncoGenex Pharmaceuticals has received an additional fast-track designation for OGX-011 as a first-line treatment for progressive metastatic prostate cancer, combined with docetaxel, and is seeking a partner for Phase III clinical trials.

The designation was granted for OGX-011, or custirsen sodium, because it may improve survival for castrate-resistant prostate cancer (CRPC), the company says in a statement Tuesday. OncoGenex expects to find a development partner by year’s end, spokesman Jason Spark told DID. OGX-11 previously received fast-track designation for use as a second-line treatment with docetaxel for progressive metastatic prostate cancer (DID, Aug. 25, 2008).

The request for fast-track designation was based on data from a randomized, Phase II study that suggest OGX-011 in combination with first-line docetaxel may improve survival. The median survival rate for patients with CRPC who received OGX-11 plus docetaxel was 23.8 months compared with 16.9 months for those who received only docetaxel, the company says.

OncoGenex says it has completed special protocol assessments for Phase III trials of the drug as a first- and second-line chemotherapy treatment.

OGX-011, the company’s lead candidate, has completed five Phase II clinical trials in prostate, lung and breast cancers. — April Hollis


Study: Antidepressants May Raise Developmental Risks for Newborns

Infants born to women who take selective serotonin reuptake inhibitor (SSRI) antidepressants while pregnant face an increased risk of being born preterm, having low Apgar scores (a standard measure of a newborn’s well-being) or being admitted to neonatal intensive care units, a study finds.

The study examined pregnant women who received prenatal care in Aarhus University Hospital in Denmark from 1989 to 2006, 329 of whom reported treatment with SSRIs, according to study results published online in the October issue of Archives of Pediatrics & Adolescent Medicine. Another 4,902 patients in the trial were not treated with SSRIs but had a history of psychiatric illness, and 51,770 reported no history of psychiatric illness.

“The study justifies increased awareness to the possible effects of intrauterine exposure to antidepressants,” according to its abstract.

This is not the first study to find risks to newborns whose mothers take SSRIs. According to the FDA’s website, a February 2006 study in the New England Journal of Medicine found that persistent pulmonary hypertension was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week of the pregnancy than among those who did not. In May, the FDA updated the prescribing information for all SSRIs with that information.

The label for one prominent SSRI, Forest Laboratories’ Celexa (citalopram hydrobromide), says that newborns exposed to that drug and other SSRIs or serotonin and norepinephrine reuptake inhibitors late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support and tube feeding.

“There are no adequate and well-controlled studies in pregnant women; therefore, citalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus,” the label says.

SSRIs also may pose risks to the pregnant women who take them. In 2006, the FDA issued a request to expand a black box warning for all antidepressants to reflect the risk of suicidality in patients under 25 (DID, Dec. 14, 2006). However, two studies published in the July 2007 issue of The American Journal of Psychiatry questioned the link between antidepressants and suicide attempts (DID, July 12, 2007).

The Archives of Pediatrics & Adolescent Medicine abstract is available at archpedi.ama-assn.org/cgi/content/short/163/10/949?home. The FDA information page “Treatment Challenges of Depression in Pregnancy and the Possibility of Persistent Pulmonary Hypertension in Newborns” is available at www.fdanews.com/ext/files/Treatment-Challenges-of-Depression.pdf. — Martin Berman-Gorvine


EC to Review Decision to Withhold GSK Anti-Competition Waiver

A ruling from the European Court of Justice (ECJ) requires the European Commission (EC) to reconsider its refusal to grant GlaxoSmithKline (GSK) an exemption from competition rules related to drug pricing.

The ECJ found that the EC failed to carry out a proper examination of GSK’s request for an exemption in a case involving differences in pricing of the drugmaker’s products in Spain and other EU member states, the court says in a statement Tuesday.

The case stemmed from an agreement between GSK and wholesalers in Spain to base prices on whether the drugs would be sold in Spain or exported to other member states and sold at higher prices. The company’s practice targeted the parallel trade of its drugs in the EU, the ECJ says in a statement.

After the agreement’s implementation, the EC ruled in 2001 that GSK’s general sales conditions were prohibited by the community competition law because they restricted competition and because the company had not proved that an exemption was justified.

A lower court threw out the EC’s ruling in 2006, and the ECJ’s decision Tuesday upheld that ruling.

The lower court “correctly held that the Commission had not taken account of all the relevant evidence produced by GSK regarding the loss of efficiency associated with parallel trade or the gain in efficiency produced by the general sales conditions,” the ECJ says.

The ruling does not guarantee that GSK’s agreement with the wholesalers will be upheld, but it does require the EC to reconsider its decision not to grant the company an exemption.

GSK did not respond by press time to a request for comment. — David Belian


FTC: New Advertising Guidance Won’t Bring Civil Penalties

The FTC’s new guidelines tightening restrictions on testimonials in advertising will not result in civil penalties for drugmakers and other companies — as some media reports have suggested, an FTC spokeswoman says.

Under the revised recommendations, drugmakers are advised to clearly disclose typical product results in advertisements that feature testimonials about unusual results. The guides, effective Dec. 1, eliminate a “safe harbor” that allowed the description of unusual product results in testimonials as long as they included a disclaimer, such as “results not typical,” the FTC says in a statement this week.

But civil penalties cannot be used as a remedy for any violations of the guides because they are not rules, Shira Modell, attorney with the FTC’s Division of Advertising Practices, told DID. Modell noted several erroneous media reports that the guides would enable the FTC to levy fines for failure to follow the new recommendations.

The FTC can seek injunctive relief and, in some cases, consumer restitution for advertising that violates the recommendations, she added. Modell noted that the guides broaden the FTC’s interpretation of deceptive advertising.

Under the guides, both advertisers and endorsers may be held responsible for false or unsubstantiated claims or for failure to disclose material connections between the advertiser and endorsers, the FTC says.

Further, if an advertisement cites results from an organization that conducted company-financed research, the advertisement must disclose the connection between the advertiser and the organization.

Pfizer spokeswoman Kristen Neese told DID that the company is reviewing the guides and is continuing to follow current FTC guidelines and regulations.

Earlier this year, an FDA draft guidance said drugmakers should focus on the overall impression their advertising conveys to healthcare professionals and consumers to determine whether each piece of promotional material complies with the law and FDA regulations (DID, May 27).

The FTC’s “Guides Concerning the Use of Endorsements and Testimonials in Advertising” are available at www.ftc.gov/os/2009/10/091005endorsementguidesfnnotice.pdf. — April Hollis


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