By Ethan Guillen and Zion Maffeo
Why can a generic for Truvada be registered now? And can it be sold soon?
The very short answer
In early June, the FDA approved generic Truvada (tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]).
In getting approval for TDF/FTC, generic pharmaceutical company Teva has asserted that it is not infringing on any patents or exclusivity. This is likely related to their earlier litigation with Gilead that was secretly settled, which in 2015 led us to believe generic Truvada might appear in late 2017. Based on the approval by the FDA, unless Gilead now sues Teva, Teva will be free to sell generic TDF/FTC and may have a 180 day exclusivity, which is a big motivator for generics to come to market quickly. Even if it doesn’t have 180 days of formal exclusivity, if it is the first to market it would have an effective duopoly until the entry of another generic that gives it a chance to make a lot more money.
Someone needs to ask Teva their plans, but in general this sort of FDA approval would indicate that Teva will begin marketing generic TDF/FTC soon, unless there is something hidden in their earlier litigation with Gilead that we don’t know about. If Teva choses not to produce and instead to help protect Gilead’s monopoly on the drug, there may be grounds for anti-competition litigation.
The long answer
Since the announcement that the FDA approved a generic version of Truvada, used as a part of treatment for HIV and the only approved treatment for pre-exposure prophylaxis to prevent HIV infection, there have been a lot of questions as to how the FDA could approve a generic from Teva Pharmaceuticals and if Teva could actually sell generic Truvada when some patents run out in 2021.
In this blog we’ll use the generic name for Truvada, tenofovir disoproxil fumarate/emtricitabine, which is abbreviated as TDF/FTC.
There are a number of things that impact when a drug can be released as a generic, but three key considerations are patents, data exclusivity, and litigation challenging patents.
The Food and Drug Administration (FDA) maintains what they call an Orange Book (back when it was a real physical book it must have been orange). The Orange Book lists all the patents that a drug company claims are relevant to a drug they produce along with any data exclusivity.
A patent gives a 20 year exclusive right to use an idea. The tradeoff is that for getting this monopoly, the patent holder is meant to disclose how you use the invention so after the 20 years the public can broadly use it. (The disclosure part often doesn’t really happen: try to figure out how to recreate Google by reading the patent on their algorithm). Drug companies usually get under 10 years of monopoly from a patent given the time it takes to get a drug to market.
The important thing to remember when looking at the Orange Book: the FDA does not do anything to verify that these patents are valid (the work of the USPTO) or actually necessary to make the drug. Just because a patent is approved by the USPTO, doesn’t mean it is valid. A huge proportion of patents that are given a second look by the USPTO (when they are challenged under certain administrative procedures) are either invalidated or narrowed in scope [something like 70% – look up the stat]. This means that a lot of patents aren’t valid. But the FDA doesn’t check that. And patents cover very different parts of the drug including the molecule that is the medicine, how it is formulated, and how it is made: patents on the molecule, the actual medicine, are in general, hard to challenge. Process and formulation patents are, in general, more susceptible to challenge.
There are many caveats to all of this, but the important thing to remember: the FDA lists whatever patents the drug company says are relevant. The company wants as many ways to block generics as possible so they have an incentive to list a lot.
Data exclusivity is also listed in the Orange Book. The data in this case is the data that a drug company collects when they run clinical trials to prove a drug is safe and effective. One reason generic drugs are cheaper is because they don’t have to run clinical trials (which would be unethical as you’d be giving a placebo to patients rather than a drug that is proven to work). They are allowed to show that the drug they make is the same as the original drug and then reference the data from the original drug company.
Data exclusivity means that for 5 years (with some variation), this data cannot be referenced to register a generic drug. Data exclusivity cannot be challenged.
So a drug can be covered by either patents, data exclusivity, or often, by both at the same time.
Litigation Challenging Patent
The USPTO often gets things wrong when granting a patent. Patents are granted under very specific conditions and can be challenged in court, and in the case of medicines, this often is carried out by generic drug companies. Generic companies have an incentive to challenge patents 1) to get to make the best new drugs and 2) if they successfully challenge a patent they get 6 months of exclusivity before other generics can make competitors – effectively a duopoly.
Sometimes the outcome is clear and the generic company loses and the patent stands or they win and a patent is eliminated. But sometimes the generic company will settle with the original drug company agreeing to drop the challenge, but agreeing in secret (often) that the generic can begin to produce a generic after a certain amount of time.
So When Can a Generic Medicine Be Registered?
So how to know when a drug can potentially be produced as a generic?
- Look at the date of expiration of the last patent in the FDA Orange Book [link to Orange Book] and the date of expiration of the drug’s data exclusivity. Take whichever date is latest.
- BUT, you then also have to look at any litigation from generic companies challenging the patents. If there are public court decisions or settlements you can understand the patent situation and potential dates when a generic version of a drug can be registered. If there are private settlements, you can sometimes still guess at when a drug will be registered as a generic.
Often based on court challenges, the date that a generic can be registered is earlier than the dates in the Orange Book.
For Truvada, the patents would show expiry in 2021, but due to patent challenges by a large number of generic companies, a number of the patents are no longer valid. Some of the settlements are secret, but there are good reasons to have guessed that a generic could be registered in 2017. You can read the long version of why, here.
It would be useful to contact Teva to see their production plans. The FDA will only approve a drug when a company believes it has the ability to produce it and it is up to the originator drug company (in this case Gilead) to sue to stop them if they don’t believe it should be sold on the market in violation of any claimed patents or exclusivity. In this case, given that Teva had a secret settlement with Gilead, we’d guess that they’ll be able to go ahead and bring the drug to market. Teva settled their litigation with Gilead either to launch their product and use the 180 day exclusivity OR because they received a ‘pay-for-delay’ type settlement and/or Teva may be hoping to park their exclusivity (a strategy to deter quick follow on of other generics). Pushing for answers seems key to ensuring the public is aware of when a generic will be available
Teva said as much in it’s application to the FDA. They asserted “paragraph 4” that claims the patent is not infringed or is not invalid. They also claim that the time to sue them has passed based on previous litigation. Whether Gilead believes that is true will be up to Gilead. But Teva may now have 180 days of exclusivity, barring any lawsuit from Gilead or entry of a second generic (the 180 days of exclusivity is complicated in this situation). There is no reason they would waste that 180 days of exclusivity or the effective exclusivity they would have by being first to market, unless they were colluding with Gilead to keep prices high, which could open them to competition complaints. The FDA notice indicated that there are issues with Teva’s “risk evaluation and mitigation strategies” (REMS) filings. How quickly Teva complies with the REMS filing requirement will likely be a good clue as to Teva’s actual generic TDF/FTC plans.
We’d expect to see generic TDF/FTC soon. Gilead is not the right target for questions as they have an incentive to make their shareholders believe it will be as long as possible. We need to be asking Teva exactly when.