An evergreening story: from Efexor to Efexor-XR to Pristiq | Pharmaguy's Insights Into Drug Industry News |

How evergreening works

Evergreening is achieved by seeking extra patents on variations of the original drug – new forms of release, new dosages, new combinations or variations, or new forms. Big Pharma refers to this as“lifecycle management”. Even if the patent is dubious, the company can earn more from the higher prices than it pays in legal fees to keep the dubious patent alive.

Evergreening is possible because in Australia the standard required to get a patent is very low. Different methods of delivering drugs (such as extended release, for example) have been known for decades. But when one of these known delivery methods is combined with a known drug, the patent office considers this sufficiently inventive to grant a new 20-year patent. Another favorite evergreening strategy is to patent a slight variation of the drug.

Brand pharmaceutical companies argue that these “lifecycle management” patents provide improved health outcomes to the community. They meet the (very low) patentability thresholds of novelty and inventiveness. Critics argue that the claimed improved health outcomes are small or non-existent.

An evergreening story: from Efexor to Efexor-XR to Pristiq

An example is useful. In the case of the depression drug venlafaxine (marketed as Efexor), the original version had major side-effects. However, when provided in extended release form these side-effects were substantially reduced.

Naturally the extended release form (Efexor-XR) became preferred. Although it might seem obvious to combine venlafaxine with an extended release form to overcome the side-effect problem, the patent office granted two new patents for extended release versions of venlafaxine.

One of these was written in such a broad form that it delayed generic entry by two and a half years, while legal wrangling took place. Eventually the evergreening patent was declared invalid. But the cost to taxpayers of this delay is estimated at $209 million.

Pfizer has a second evergreening strategy for venlafaxine. When venlafaxine is taken, the human body converts it to desvenlafaxine. In other words desvenlafaxine is a variant of the original active pharmaceutical ingredient venlafaxine. Clearly the two compounds are closely related. So it is astonishing that desvenlafaxine passed the tests for getting a patent.

Desvenlafaxine is marketed as Pristiq. Pristiq entered the market early in the two-and-a-half-year period of legal wrangling over the extended release venlafaxine (Efexor-XR) patent. Pfizer’s marketing of Pristiq in February 2009 was so lavish that it attracted the attention of investigative journalists.

Pristiq has no additional benefits for patients. Despite this, during the first six months of 2014 half of prescriptions were written for Pristiq rather than for the clinically identical Efexor-XR.

But Pristiq costs between $A 22.32 and $A 26.50 more than Efexor-XR, depending on the dose. Based on reported prescription volumes in 2013-14, the cost to the taxpayer of doctors prescribing Pristiq rather than Efexor-XR exceeds $21 million a year.

Unless generic companies challenge the desvenlafaxine patent, there will be no generic versions of Pristiq until after August 2023, when the patent expires.