Transparency? AbbVie Sues EMA Over Trial Data

In a direct challenge to the proponents of disclosing clinical trial data, AbbVie has filed a request for an injunction to prevent the European Medicines Agency from releasing detailed patient-level data from studies concerning its top-selling Humira rheumatoid arthritis treatment, The Financial Times writes.

The filing comes after two Freedom of Information requests were made to the EM last year to release “raw data” on the safety and efficacy of the medication, a multi-billion-dollar seller. One of those filings was made by UCB, which sells a rival treatment called Cimzia. A similar filing with the EMA was also lodged by InterMune and the US and European industry trade groups filed supporting pleas, the paper writes.

The move comes amid a heated controversy over data disclosure, which most drugmakers are fighting over concerns that confidential information could be unfairly obtained by rivals. On the other side of the debate are researchers who argue that results cannot be independently verified unless patient-level data and case-study reports are fully disclosed.

In a statement, the drugmaker says it is “seeking to protect AbbVie’s confidential and commercially-sensitive information,” according to the paper. Abbvie supports “transparency of clinical research and safety information for the benefit of patients and healthcare professionals, (but not) the disclosure of commercially confidential information that does not meaningfully contribute to the scientific review or evaluation of our products.”

There are, however, cracks showing in the stance taken by the pharmaceutical industry. Last year, GlaxoSmithKline (GSK) agreed to make patient-level data to independent researchers, a step that came after the drugmaker paid a $3 billion settlement to settle civil and criminal charges that included a failure to release trial data (see this). However, the drugmaker has not yet launched its effort.

Meanwhile, Roche (RHHBY) recently declared it will work with an “independent” group of “recognized experts” to evaluate and approve requests to access patient-level data and will also support the release of case study reports for all of its licensed medicines. This move, which came in response to a flap over Tamiflu data, has been met with skepticism, though (read more here and here).

The Tamiflu debate subsequently prompted the British Medical Journal, known as BMJ, to issue a policy in which studies will no longer be published unless patient level data is made available. BMJ is also one of several organizations sponsoring the AllTrial campaign, which is an online petition calling for drugmakers to make public all trial data (look here). PhRMA, in particular, blasted the effort (back story).

It is unclear what the AbbVie move will mean for the EMA, which last year agreed to publicly release by the start of 2014 all submitted data once a decision has been made either to approve or reject a medicine. The agency noted, by the way, that most Freedom of Information requests for data come from rivals, not independent researchers, the paper writes.

Last month, the lead legislator for the Environment, Public Health and Food Safety Committee in the European Parliament wants to toughen proposed legislation that is designed to bolster clinical trial practices and activities on the continent. One provision would require disclosure of full clinical studies – not summaries – to be submitted (read here).

This is not the first time that AbbVie has cited concerns over trade secrets to thwart competitors. Last year, Abbott Laboratories (ABT), which has since spun off AbbVie, (ABBV) filed a citizen’s petition with the FDA to ask that the agency not approve any biosimilar for its Humira treatment for rheumatoid arthritis. The drugmaker argued the FDA would have no choice but to use trade secrets submitted to the agency when approval for Humira was first sought (back story).

14 Comments

Mar 11, 2013 - 7:44pm
We all know the real reason why the pharms don't want the clinical trial data released - all the dirty little secrets about side effects and lack of efficacy would pop out.

Here's hoping that real life tests of efficacy and anecdotes of safety become the new "Gold Standard", as opposed to doctored clinical trial data spun by marketers and "opinion leader" doctors, let alone ads.

Mar 11, 2013 - 8:55pm
Janet, it's all there in the NDA. If you want patient level data, and your concern is safety, then the Integrated Safety Summary is required to have a written summary of each patient that experienced a serious adverse event. We should send out the ISS to make publically available along with all similar postmarketing safety summaries so that you can see for yourself. No dirty little secrets, Janet. Just get a regulatory professional to review with you. They are written in technical language, with real medical terms.

From this and other posts you seem pretty paranoid that my industry is trying to pull the wool over your eyes. Trust me, we are not. I swear on the graves of my deceased ancestors.

I must say this all looks very strange.

I could understand someone fighting disclosure of patient level data on legal grounds if it were about patient confidentiality, but that doesn't seem to be what AbbVie are claiming. They seem to think that there will be a release of "commercially confidential" data.

I really struggle to imagine what that "commercially confidential" data might be. We all know how a clinical trial is run. Once a drug is marketed, then all the important stuff is in the public domain anyway. The details that remain confidential at that stage seem unlikely to be of any great commercial value.

I shall watch this case with interest.

Mar 12, 2013 - 8:54am
Adam, protection of trade secrets has long enjoyed legal protection. Clinical trial data can generate unexpected efficacy findings in the course of looking at a different objective. This in turn may generate further hypothesis testing in a subsequent trial for an additional indication. If you look at the anti tnf's, this has been their history, starting with RA and additg multiple indications later on.

This is not theory, it happens. You want to protect this new information, and it might well be generated by the data that is being sought in this case.

Thanks for those thoughts, OII, that does sound vaguely plausible.

If that is what's happened here, then it seems that there could be quite a tricky balance to be struck. On the one hand, patients have a right to know what the drug they're taking is likely to do, but on the other, I agree that if there is genuinely commercially sensitive information it needs protection.

It would seem to me that a reasonable compromise might be some kind of time delay to allow the originator company time to look into the unexpected findings, but then to allow the data to be released after that time has expired. Will be interesting to see what the courts decide.

Mar 12, 2013 - 2:53pm
Adam when you say "vaguely possible" I take that as a compliment. Most posters are so blinded by their abject hatred of pharma and everything it stands for that they are patently unwilling to entertain anything that might not only be plausible but scientifically verifiable. Their contempt knows no limits as repeatedly demonstrated by their plaintive uninformed blathering on a regular basis .
Mar 12, 2013 - 5:32pm
@oii - "...This is not theory, it happens. You want to protect this new information, and it might well be generated by the data that is being sought in this case...."

You crack me up. That "new information" was widely distributed to sales and marketing to start all those "off-label" campaigns that got everyone in trouble!

As soon as someone inside the pharma co. thought it was "plausible" everyone went off running with it, so how can you justify not releasing that data when you were already "commercializing" it in off-label campaigns?

Mar 12, 2013 - 8:12pm
As a disciple of Bert Spilker and Controlled Clinical Trials, I pledge allegience to the time method of testing hypotheses that may be generated serendipitously from clinical trials. In fact I would strongly oppose the off label dissemination of new untested efficacy findings inasmuch as it puts the information in the public domain and may therefore jeopardize future patent protection if a new indication is obtained.

On the other hand if off label promotion can bring in huge coin and jacks up my bonus, then I see nothing, hear nothing and say nothing.

Mar 20, 2013 - 8:12am
@oii "protection of trade secrets has long enjoyed legal protection. Clinical trial data can generate unexpected efficacy findings in the course of looking at a different objective. This in turn may generate further hypothesis testing in a subsequent trial for an additional indication."

There doesn't seem to be any logical justification not to release full clinical study reports once a drug company has obtained regulatory approval.

Under most national patent laws, pharmaceutical companies must choose between trade secrets and patent protection. They cannot have both. They already have patent protection over the molecule, and full details of how to manufacture the drug are contained within patent specifications already (in order to satisfy the "enablement" requirement for patentability).

Therefore, it is uncertain what kind of "trade secrets" could be contained within clinical study reports which a competitor would be able to exploit? (1) To the extent that information is publicly available, a competitor would be unable to file a patent over new indications contained in any clinical study reports (2) Even if a competitor did file a patent, they would be unlikely to spend money on getting regulatory approval over the new indication for the same drug, because their "method of use" patent would be more susceptible to invalidation (3) The original sponsor could use their own patent over the molecule (or data exclusivity) to block competition.

I am genuinely curious as to why AbbVie is suing the EMA. What do they lose if the clinical trial data is released? What is the nature of these "trade secrets" they are so worried about? It all seems a bit mysterious. It seems they are probably more worried about various researchers conducting independent analyses of the data which might impact negatively on sales (and require them to waste money on conducting more of their own expensive clinical trials to counteract these findings).

Mar 20, 2013 - 9:01am
SK - Your statements are not entirely accurate. A patent enables one skilled in the art at the time of the invention. Typically, this is bench scale chemistry. A patent need not teach the best way of making kilogram quantities of the API nor the final dosage form that include the API.

This information is generally manufacturing know-how and is regarded as trade secrets. One reason why the CMC section of NDAs are kept in confidence, they typically have manufacturing know-how in them.

Thus, patents and trade secrets are nto mutually exclusive. They go hand-in-hand.

Second, what I believe OII is getting to is that a secondary endpoint may lead to further studies of a different indication for the drug. If all clinical trial data were published, this information would likely render obvious (in a patent sense) the second use of the drug, destroying the monetary incentive to investigate it.

Mar 20, 2013 - 9:12am
SK you are assuming that secondary efficacy findings that the company wishes to maintain as trade secrets may only impact the immediate competitive environment. Clinical development plans are developed over periods of many years, thus the innovator may well wish to keep trade secrets in their back pocket for 5-10 years while they are formulating a strategy around commercializing their new discovery. For my money theier is no time limit or value limit on a potentially important trade secret.

Once in the public domain you lose your competitive advantage.

Mar 20, 2013 - 7:01pm
@Xtian

Simple solution to this problem - keep the CMC/"manufacturing process" part secret but release the rest of the clinical trial data.

Regarding the composition and dosage of the API, surely, this is already in the public domain or at least can be reverse engineered limited expenditure - maybe a few million - not a major outlay for most generic companies.

"Second, what I believe OII is getting to is that a secondary endpoint may lead to further studies of a different indication for the drug. If all clinical trial data were published, this information would likely render obvious (in a patent sense) the second use of the drug, destroying the monetary incentive to investigate it."

Innovator companies already have limited incentives to investigate new indications/uses - particularly as doctors are legally able to prescribe drugs off label and such patents are easier to invalidate. However, second use patents are more valuable in countries where governments subsidise the cost of medicines (and the medicine is expensive) as they will not subsidise use of a generic product for a patented indication.

@oii - As I mentioned before, new indications have limited commercial advantages so the value of keeping them secret is doubtful. Manufacturing processes can be excluded from the clinical trial data, if necessary.

In any case, if the innovator were to research clinical trials over new indication they could get 3 years data exclusivity in the US and another year in the EU irrespective of a method of use patent, which would probably be invalidated anyway.

If clinical trial data was publicly available innovator companies would be incentivised to research all possible indications for a drug to maximise their sales while they had market exclusivity. Currently, as you mention, they are incentivised to "keep trade secrets in their back pocket for 5-10 years" and then "evergreen" protection over their drug with a method of use patent just before the composition of matter patent runs out.

Mar 20, 2013 - 8:21pm
SK is correct in that my strategy would best work early in the life cycle of the product. It would not make as much sense to keep a great idea in your back pocket near the end of the cycle if it will be used for that indication off label once the product goes generic. Good catch.
Mar 21, 2013 - 12:50am
@oii

If the innovator already has market exclusivity over the API and can't rely on method of use patents to recover their investment in clinical trials for second uses, what's the point of maintaining "trade secret protection" for secondary efficacy findings?

It seems the public interest would be better served by full disclosure.