Regulatory Focus™ > News Articles > French Regulator and Roche Trade Blows Over Off-Label Avastin Use

French Regulator and Roche Trade Blows Over Off-Label Avastin Use

Posted 25 June 2015 | By Michael Mezher 

French Regulator and Roche Trade Blows Over Off-Label Avastin Use

On Monday, Swiss drugmaker Roche announced its opposition to the use of its cancer drug Avastin to treat wet age-related macular degeneration (AMD) in France. The move is aimed squarely at France's drug regulator, who temporarily recommended the drug for AMD as a cost saving maneuver in April 2015.


Health authorities around the world have been eyeing Avastin (bevacizumab) as a cheaper alternative to Novartis' Lucentis (ranibizumab injection).

After being approved in the US and Europe in 2004 and 2005, respectively, Avastin has been widely used off-label to treat AMD. However, two years later, Lucentis became the first authorized drug indicated to treat AMD.

Because Lucentis costs about 30 times more than Avastin, and the two drugs are thought to be similarly effective, several prominent health authorities—including the World Health Organization (WHO), the International Council of Ophthalmology (ICO) and the National Eye Institute (NEI)—have supported using Avastin to treat AMD.

Despite international pressure, Roche has resisted expanding Avastin's indication, maintaining its stance that Avastin should not be used to treat AMD.

Roche's stance has been controversial, as the company owns a stake in both Avastin and Lucentis. Both drugs were discovered and patented by Genentech, which Roche acquired in 2009. However, in 2003, Genentech and Novartis made an agreement in which "Novartis received exclusive development and marketing rights for Lucentis outside the United States."

Both Roche and Novartis are being investigated by antitrust authorities in Europe over their marketing practices related to Avastin and Lucentis. In 2014, the Italian Competition Authority found the companies had conspired to drive sales of the more profitable Lucentis, and fined the companies a combined €180 million.

Temporary Recommendation

In July 2014, French lawmakers voted in favor of substituting Avastin for Lucentis. The move drew harsh criticism from the pharmaceutical industry, which viewed it as a means of undermining the regulatory process and a threat to patient safety.

Shortly after, France's medicines regulator, l'Agence Nationale de Sécurité du Médicament (ANSM), wrote to Roche requesting data from the company regarding Avastin's use in treating AMD. In March 2015, an ANSM benefit/risk assessment commission, having reviewed "various trials and meta-analyses," issued a temporary recommendation of use (RTU), allowing Avastin to be used to treat AMD.

In France, an RTU is a procedure that allows ANSM to recommend an authorized product for additional indications outside of its marketing authorization.

Prior to December 2014, an RTU could only be used when:

"There is an unmet therapeutic need, i.e., there is no appropriate alternative medicine with [a marketing authorization] or a cohort [temporary authorization for use (ATU)] in the indication in question," and "the benefit/risk ratio of the medicine is assumed to be favourable based on the available scientific efficacy and safety data."

However, in December 2014, the French Public Health Code was amended to allow an RTU to be issued when there is no alternative product for a given indication with the same active ingredient.

Renewed Opposition

In a press release Monday, Roche reaffirmed its opposition to the RTU issued by ANSM, and said the company should not be beholden to EU pharmacovigilance requirements for Avastin when it is used to treat AMD. Roche has also defended itself in the press, saying that it does not have "the expertise nor capacity or authorization" to repackage Avastin in quantities appropriate for ophthalmologic use.

Because the dosages of Avastin are much higher when used to treat cancer, doctors administering the drug must use smaller quantities of the drug, either by obtaining repackaged doses or measuring out fractions of a vial. While this may seem like a simple task, both scenarios pose an increased risk for serious eye infections if not done properly.

In response to Roche's statement, ANSM has reminded the company that it is required to monitor its product's use, even under an RTU, according to the French Public Code of Health.


ANSM Statement (French), Roche Press Release (French)

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