Gilead made misleading and illegal statements about Viread, says FDA
Graham McKerrow, HIV i-Base
Gilead Sciences Inc has been instructed by the US Food and Drug Administration (FDA) to stop making what it says are misleading and illegal statements to promote the drug tenofovir, sold as Viread. Representatives of the company claimed it was a “miracle drug” and they minimised important risk information, says the FDA.
The FDA has written to the company ordering it to stop making the “violative statements”, not to distribute promotional material containing the statements, and to reply to the FDA in writing.
The company says it has never made the statements in promotional material. However, the FDA “identified promotional activities that are in violation of the Federal Food, Drug and Cosmetic Act and its implementing regulations,” writes Laura Pincock, Regulatory Review Officer of the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) in a letter sent to Gilead in March.
Gilead representatives made the suspect statements to DDMAC representatives at the ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) in Chicago in December last year, writes Pincock. Her letter says one company representative said the drug had “no toxicities”, was “extremely safe” and “extremely well tolerated” – statements the FDA describes as “false or misleading”.
The boxed warning on Viread’s approved product labeling says that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Pincock says two Gilead representatives claimed this was “a product class warning, and there are no problems but it was put into the product labelling as a ‘wait and see’ warning.”
The representatives also said, according to Pincock, that Viread “does not affect mitochondria; therefore you would not expect to see lactic acidosis.”
Further, the letter says the company representatives told the DDMAC reviewers that the warning “is a class effect” and “our product labelling is the only one that does not name the drug because Viread is a nucleotide, not a nucleoside.”
Pincock writes: “These statements are in violation of the Act because they minimise the boxed warning for Viread and misleadingly suggest that the drug is safer than has been demonstrated by substantial evidence. In fact, there have been case reports of lactic acidosis in patients receiving Viread in clinical trials and the expanded access programme.”
Pincock adds in her letter: “Furthermore, Viread functions as a nucleoside analogue and, therefore, carries the same class warnings as other nucleoside reverse transcriptase inhibitors.”
A fourth Gilead representative is criticised by Pincock for overstating Viread’s efficacy by saying the drug “is approved for a broad indication” and characterising it as a “miracle drug”. Pincock tells the company: “In fact, Viread was approved by the Food and Drug Administration under accelerated approval status, and the clinical benefit of Viread in HIV patients has not yet been determined.” Pincock underlined the last part of that sentence.
A press officer for Gilead, based at Foster City, California, said the company took Pincock’s letter very seriously and was trying to identify the company representatives concerned. It has never published promotional material containing the statements Pincock complains about, she said, adding that the company has sent a reply to the FDA.
Viread is a once a day drug approved by the FDA in October for use in combination anti-HIV therapy. It is the first nucleotide drug – a group of drugs similar to nucleosides – to be approved for antiretroviral therapy.
Full text of FDA warning letter to Gilead available as a PDF file at:
The Gilead marketing department and publicity machine are understandably in full swing following the approval of tenofovir. It is sad, however, that the provision of accurate and cautious information on this drug appears to have taken second place to marketing spin and overdrive.
There has been relatively little use of tenofovir so far in clinic, with small numbers of patients exposed to this novel agent. Approval under accelerated procedures is also notorious in failing to identify longer term toxicity concerns with antiretrovirals. Such inflated claims and the downplaying of concerns over toxicity highlighted by the FDA do little to enhance the standing of this pharmaceutical company with treatment advocates, prescribers and patients.
A further example of this seemingly inappropriate behaviour by Gilead was evident after the recent Retrovirus Conference when the company circulated a press release with the grand title “Viread Demonstrates Anti-HIV Potency Similar to the Protease Inhibitor Ritonavir in Short-Term Study of Treatment-Naive Patients”. This presentation of a short-term monotherapy study did indeed demonstrate that tenofovir produced comparable viral load drops and decay rates to ritonavir when dosed as a monotherapy agent for 21 days in antiretroviral naïve subjects – 80% of whom were non-Caucasian (we’ll leave aside the ethical implications of such a monotherapy study for the moment as well as the fact that the ritonavir “potency” was not a direct comparison but was determined from historical data).
Perhaps “Anti-HIV Potency”, however, might for most critical readers encompass somewhat more than a 21 day fall in plasma viral load. Ritonavir is one of the few antiretrovirals which has demonstrated improved survival in patients with advanced HIV-disease and impressive durability of response as part of triple combination regimens despite considerable tolerability difficulties when dosed as the sole protease inhibitor. It would seem to us that Gilead, in the wording of this press release, may be attempting to suggest that tenofovir might be suitable to replace protease inhibitors as a component of triple combination therapy.
Of course such interpretations are themselves subjective and perhaps we are being oversensitive. Why not judge for yourself?
Gilead press release on the “impressive” potency of tenofovir available at: