The European Medicines Agency published a draft guidance for clinical trial transparency in 2013, and the agency scored a win recently at the European Court of Justice in what appears to be the first legal challenge of transparency to reach the ECJ. The decision in the case of Pari Pharma v. EMA affirms the legal standing of this practice, but the decision also makes clear that broad assertions of confidentiality and unsupported claims of damaged commercial interests will not sway the European Union’s high court.
Novartis, Pari in Nebulizer Standoff
EMA announced early in February that the court had declared that three companies, including Pari Pharma of Starnberg, Germany, had no legitimate claim that the disclosures of their data constituted a compromise of intellectual property. The court’s decision makes clear that Pari’s cause was thwarted by Novartis, which along with the French government pushed the court to side with EMA in the dispute.
Novartis’ interest in the market for tobramycin nebulizers was driven by its Tobi Podhaler, which like Pari’s Vantobra aerosol is indicated for pediatric cystic fibrosis. According to an earlier court document, Novartis had acquired a marketing authorization for the Tobi via an orphan product designation in 1999, but subsequently received an extension of marketing exclusivity through 2023.
Pari had claimed its product offered superior safety, and won that debate in 2015, when EMA granted the product a CE mark. The EMA’s decision summary makes clear that the European Commission had misgivings about how EMA had interpreted orphan product legislation on the point of product similarity, but in any event, Novartis lost its exclusivity for this treatment and indication.
No General Presumption of Confidentiality
Pari’s argument before the ECJ seems to revolved in part around the notion that the information found in its filings enjoyed “a general presumption of confidentiality,” an argument the court found unpersuasive. Pari also argued that both publicly available and confidential information together would disclose the company’s proprietary strategy for obtaining marketing authorization. The Court replied that this purported strategy was enabled in part by an exchange with the EMA as “part of a specific regulatory process” and consequently not entitled to discretion.
Pari further asserted that its strategy constituted intellectual property as defined by the 1995 Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), but the Court would have none of it, in large part due to the fact that much of the information in question was already in the public domain. The Court said also that knowledge of the effect of the use of a nebulizer on intolerance to dry powder “could be obtained without difficulty and without any particular inventiveness.”
Pari fared no better on the confidentiality of its patient survey data, either, largely because the data set included information drawn from a patient registry set up by the European Cystic Fibrosis Society. According to the court, much of Pari’s survey data was little or nothing more than a “refinement” of the ECFS registry data. Much of Pari’s problem with the ECJ was due to what the court said on several occasions was as a failure to demonstrate any damage to the company’s commercial interests stemming from the disclosure.
There were two other cases in this clutch of losses on the transparency question – PTC Therapeutics fared no better over disclosure of data related to its treatment for Duchenne muscular dystrophy, Translarna (ataluren) – but only time will tell whether drug and device makers will eventually score a win at ECJ over the EMA transparency paradigm. In any event, Pari’s experience makes clear that nebulous arguments and better nebulizers won’t win the day at the European Union’s high court.
The Difference Between Faster and Earlier
To some, the term “regulatory harmonization” might suggest more or less simultaneous approvals across jurisdictions, but a recent study of drug approvals by three regulatory agencies hints that this dream is still just a dream. There are confounders in the latest study of drug approvals, however, including that the approved indications are anything but identical.
The Feb. 22 issue of the European Journal of Clinical Pharmacology states that the FDA, Swissmedic and the European Medicines Agency approved a total of 134 new drugs between 2007 and 2016. The FDA is credited with being the first to approve 66.4 percent of these, while the EMA was the first to approve nearly 31 percent, leaving Swissmedic with a paltry three percent first-to-approve rate.
While this report has gained some traction in the trade press, non-subscribers to the journal have only the abstract to rely on, which states that the approved indications were similar in only 23 percent of the drugs across all three agencies. The differences between the Swissmedic and EMA approvals were few, while the differences in labeled indications between the FDA and EMA were “significant.”
Obviously it is difficult to know what to make of this information without knowing how those labeled indications varied, but another absent piece of this puzzle is the total premarket review time for each drug at each agency. It’s one thing to say that agency A approved a product sooner than agency B, but it’s quite another to say the total review time was shorter. Without that context, this abstract has little to offer.
As might be expected, the total review time question has its own moving parts as this study in the New England Journal of Medicine suggests. The authors of this write-up from April 2017 indicate that cancer therapies and orphan drug applications moved more swiftly through the FDA premarket process than was seen in the EMA process, but that does not apply to all drug types or drug application types. The take-away from all this is that comparisons remain nettlesome and often are not particularly informative.