BioPharma, Pharma

Precision medicine’s chicken and egg problem

A senior researcher from Janssen Research & Development laments the slow progress of precision medicine while one points to the budgetary challenge it poses as quintessentially a chicken and egg problem.

Chicken with eggs in nest

Companion diagnostics is gaining currency as novel drugs are being paired up with tests that determine which patients will have a higher chance of  responding to that drug.

But 15 years after the human genome project has been completed, the progress of precision medicine appears to be woefully slow, at least according to Nicholas Dracopoli, vice president and head of Oncology Biomarkers at Janssen Research & Development, part of Johnson & Johnson. Others believe precision medicine and companion diagnostics have a chicken and egg problem.

Dracopoli was a speaker at the Precision Medicine Leaders Summit that concluded last week in San Diego. A recent study that analyzed various criteria for measuring success of drug development formed the basis of Dracopoli’s opinion on precision medicine.

The study found that the probability of a drug approval jumped three-times to 25.9% for drugs that were approved with a predictive biomarker, from 8.4% for drugs without one. See the extreme-right bar from the study below:


“What it showed was across all therapeutic areas and this is literally across hundreds of approved drugs over the course of 2006 to 2015, there was a three-fold increase in success as determined by FDA registration if you had a predictive marker in your development strategy,” Dracopoli said. “We would beg for a three-fold increase in success. You could change the entire finance and underlying business model for pharmaceutical R&D if you consistently obtained a three-fold increase in productivity.”

Given this datapoint, it would seem obvious that more drugs today would come with companion diagnostics than without.

“This would argue that if I can get a three-fold better chance of my getting my drug approved if I had a predictive marker then you would predict that most drugs getting approved would have one, but that is absolutely not the case,” Dracopoli declared.

The proportion of oncology drugs approved being developed with a companion diagnostics has been increasing since 1998 when the first such drug/companion diagnostics was approved — Herceptin for breast cancer. However, they still constitute a very small minority of oncology drugs approved overall. In fact, between 1998 and 2015, only 20 of 159 oncology drugs come with a companion diagnostic or predictive biomarker, Dracopoli pointed out.

“Twenty drugs doesn’t sound like very many. It’s actually worse if you look at the number of targets,” he said, before adding. “So, here we are some 15 years after the completion of the human genome sequence, and we can essentially make predictive markers against only six targets.”

And that in Dracopoli’s mind falls short of the ambitions that were set in motion when the human genome was mapped.

“I would argue that that is not a success, and that our ambitions for the genome project 15 years ago [are] clearly disappointed at this level of productivity,” he lamented.

Part of the problem is the pharma R&D budget. A life sciences consultant, who was not at the conference, described the conundrum of drug development with companion diagnostics as a “chicken and egg” problem.

“A lot of companies that would be developing a companion diagnostic need to understand the molecular basis of the disease in order to test something and often they have to develop something in parallel using diagnostics development and assay development testing in all of the diagnostics realm of the world. [But] they often are hesitating to invest in that before they know they have efficacy or signs of efficacy in the drug [being developed],” said Laurie Halloran, CEO of Halloran Consulting Group, which is based in Boston, in a phone interview.

And then there is the complicated world of reimbursement.

Many payers don’t see the value of expensive esoteric diagnostic tests and are reluctant to pay for it. Even aside from Halloran who pointed out this challenge, several speakers at the Precision Medicine Leaders Summit raised the issue of reimbursement.

Most notably it was Dietrich Stephan, chairman, Department of Human Genetics at University of Pittsburgh, who charged several times that clinical utility should ultimately decide coverage and not some “peripherally connected individuals driven by piecemeal economic decisions.” That was a not-so-veiled allusion to insurance companies that do not care for patients but yet have authority on what novel therapies and diagnostics patients can access.

Yet, the disapproval of payer tactics wasn’t universal at the conference.

“I agree with much of what Stephan said initially, but I can’t fault too much the payors,” said Stephen Kingsmore, president and CEO of Rady Children’s Institute for Genomic Medicine at Rady Children’s Hospital, to the audience. “We need to give them high-quality evidence that this truly scales. Until we do that, it may be too premature to feel badly about the lack of reimbursement.”

So, while precision medicine is promising and exciting, to actually move the needle in healthcare, it has to demonstrate scale, which so far it hasn’t.

Photo Credit: Getty Images, David De Lossy