It is going to take a village to advance precision medicine

Faced with more than 80 million genetic variants that may or may not affect a person's health or risk of disease, the FDA is realizing that it will take a village in the cloud to expand its current regulatory borders and deliver the promise of precision medicine.

Known as precisionFDA, this planned community will create an environment for next-generation sequencing (NGS) test developers, researchers and others to work together to test, pilot and validate new approaches, advancing the science to develop the standards and tools that will serve as the infrastructure for precision medicine, according to the FDA's Taha Kass-Hout and David Litwack.

The agency hopes to open the doors to the first residents of its new cloud-based village in December. As envisioned, the community will give members "access to secure and independent work areas where, at their discretion, their software code or data can either be kept private or shared with the owner's choice of collaborators, FDA or the public," Kass-Hout and Litwack said in an agency blog Wednesday.

Initially, the community's public space will include a wiki, open-source or open-access reference genomic data models and analysis tools developed and vetted by the National Institute of Standards and Technology and other standards bodies.

One of the biggest challenges of precision medicine is sifting through the more than 80 million genetic variants that have been found to date in the human genome and understanding their role in health and disease. While NGS tests can quickly sequence an individual's genome, how that data are searched for potentially meaningful differences and interpreted is forcing the FDA beyond its regulatory comfort zone where it evaluates a diagnostic's accuracy and clinical interpretation based on one test for one disease.

"Because NGS tests may be used in many ways in the clinic and can produce an unprecedented amount of data about a patient, we are working to evaluate whether a better option might simply be requiring each NGS test developer to show that the test meets certain standards for quality," Kass-Hout and Litwack said. That would necessitate strong quality standards.

The FDA also is assessing whether it would be more efficient for NGS developers to refer to evidence in well-curated, validated, shared databases of mutations rather than independently generating the data to support a mutation-disease association.

Both proposals would benefit from the village in the cloud.

Given the discussions at recent workshops and conferences on the importance of collaboration in advancing medical science, the FDA is sure to have researchers willing to inhabit its new cloud community. Speaking at an FDA-Brookings Institution conference last week on improving productivity in drug R&D, Christopher Austin, director of the NIH's National Center for Advancing Translational Sciences, listed greater collaboration in both the public and private sectors as one of the transformational approaches needed to develop new therapies and tests. (See BioWorld Today, July 29, 2015.)

"Much is known," he said, "but unfortunately in different heads."

That's true among companies, as well as individuals, Paul Morgan, head of translational safety at Astrazeneca plc, said, adding that no one company will have all the expertise in a given field.

Making another case for greater collaboration, James Barrett, chairman of Drexel University's Department of Pharmacology and Physiology, pointed out that diseases such as cancer and Alzheimer's can't be treated by focusing on a single target. Instead of the single target-based therapy, collaboration is needed to develop systems-based approaches, he said.

EN BANC SOUGHT

Pushing back against an expansive Third Circuit decision that could make it nearly impossible for drugmakers to settle patent disputes, the Washington Legal Foundation (WLF) is urging the appellate court to rehear, en banc, King Drug Co. of Florence Inc. v. Smithkline Beecham Corp.

The current standard for review of drug patent settlements, the "rule of reason," was set by the Supreme Court's 2013 decision in FTC v. Actavis. In that reverse-payment case, the high court held that a settlement is subject to antitrust scrutiny if it includes a large, unexplained payment from the brand drugmaker to a generic company. (See BioWorld Today, June 18, 2013.)

However, the Actavis ruling also created a safe harbor of sorts for other types of patent settlements between drugmakers. "The fact that a large, unjustified reverse payment risks antitrust liability does not prevent litigating parties from settling their lawsuits," the Supreme Court said.

A Third Circuit three-judge panel recently expanded on the high court's ruling when it held that any benefit the brand company provides triggers antitrust scrutiny, the WLF asserted, adding that the decision conflicts with Actavis, which involved a cash payment.

Smithkline resulted from a patent settlement in which the brand company promised not to market an authorized generic (AG) of its anti-epileptic drug Lamictal (lamotrigine). The settlement with Teva Pharmaceutical Industries Ltd. was reached after a judge ruled the main claim in the challenged patent was invalid, according to court documents.

The Third Circuit panel said a no-AG agreement "falls under Actavis's rule because it may represent an unusual, unexplained reverse transfer of considerable value from the patentee to the alleged infringer and may therefore give rise to the inference that it is a payment to eliminate the risk of competition."

Calling the decision a "misguided application of antitrust law," WLF Chief Counsel Richard Samp said the Third Circuit ruling "will render it virtually impossible to settle drug patent litigation."

The decision is not surprising. Prior to Actavis, the Third Circuit had held that all pay-for-delay, or reverse-payment, settlements were, on their face, anticompetitive. (See BioWorld Today, July 18, 2012, and Aug. 28, 2012.)

HHS FINALIZES INFLUENZA RULE

The Department of Health and Human Services finalized a rule establishing an injury table that enables compensation for serious physical injuries scientifically presumed to be directly caused by covered pandemic influenza countermeasures.

In addition to listing the serious injuries caused by a specific pandemic influenza countermeasure, the table includes the time interval in which the first symptoms must appear, a definition of the injury and the level of severity necessary to qualify as a covered injury.

"Serious injuries" are those that warrant hospitalization or that lead to a significant loss of function or disability, the HHS said in a notice slated for publication in Friday's Federal Register. Individuals with injuries not listed on the table may still pursue claims by demonstrating that the covered countermeasure directly caused the injury.

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