Avastin Side Effects Reported in Off-Label Use

Genentech, Inc., manufacturer of the lung and colon cancer drug Avastin, has been linked to reports of serious eye inflammation when used "off-label" to treat wet macular degeneration, a potentially blinding eye condition.

Genentech, Inc., sent a letter on December 19, 2008 to doctors about several recent reports of intraocular inflammatory reactions that occurred after the medication was injected in lower doses to the eye, which is not an approved use of the drug.

As of December 8, 2008, the drug maker indicated that they were aware of 36 reports of adverse events associated with use of the drug to treat eye conditions, and 32 of those cases involved severe eye inflammation. These adverse reactions were reported by four different sites in Canada between November 4th and November 20th, 2008.

Avastin was approved in 2004 for treatment of non-small cell lung cancer and colorectal cancer when combined with chemotherapy. The drug inhibits tumor growth by preventing the formation of new blood vessels which nourish the tumors.

Although Avastin is not approved for treatment of eye conditions such as wet macular degeneration, doctors are free to use medications "off-label" for purposes that are not approved by the FDA.

Avastin Controversy
The disclosure comes a year after controversy erupted when Genentech yanked distribution of Avastin to compounding pharmacies, which were repackaging and selling the drug to opthalmologists for treating wet macular degeneration. Unlike Avastin, Genentech's similar, but newer Lucentis drug was approved two years ago to treat the disease, but at $2,000 a dose, is about 50 times more expensive in comparable doses.

Wet macular degeneration is a potentially blinding eye condition that occurs when new blood vessels start to form under the retina causing hemorrhage, scarring, swelling and central vision loss. Along with the dry type of macular degeneration, the conditions affect over 6 million Americans.

Side effects of Lucentis are known to cause eye inflammation in about 2% of the patients, and it is not clear whether the risk is greater when Avastin is used "off-label" in lower doses.

Of the 32 reports of Avastin eye inflammations disclosed, Genentech indicates that 25 of the events were linked to patients who received the injection from the same lot (B3002B028). However, intravenous use of Avastin has not revealed any unusual reporting patterns associated with this lot and the drug maker indicates that all quality specifications for the lot were met.

After outcries and bad publicity over last year's controversy, the biotech eventually struck a deal with opthalmologists to loosen the restrictions, but not before entering into a dispute with the FDA over its original move, which also prompted an investigation by the US Special Senate Committee on Aging into Medicare expenditures for Avastin. The NIH, meanwhile, is conducting a head-to-head clinical trial in which both drugs will be tested for treating the eye disease.