Waiting for the dust to settle: the future of drug development

Rebecca Aris interviews Christopher-Paul Milne

Tufts Center for the Study of Drug Development

The ever shifting challenges to drug development present a constantly evolving landscape. Christopher Milne of Tufts Center for the Study of Drug Development is only too aware of the challenges and changes seen in recent years.

Christopher, who recently spoke at the Best Practice in Phase IV Clinical &amp, Observational Research conference spoke with pharmaphorum to offer his insights on drug development trends that have emerged in recent years.

Christopher’s view is that with so many significant recent changes in drug development the resultant chaos is hard to draw predictions from as to where the market will head. He is sure, however, that when the dust has settled, the future will be positive. He also discusses why he thinks we are heading slowly but surely towards an era of personalised medicine.

To listen to the full interview, please click on the play button below, with a shortened transcript of some edited highlights shown in print below.

Interview summary

RA: Hi Christopher, can you please start by telling me about your background and how you came to be in your current role?

CM: Originally I got into the medical field through veterinary medicine, although I grew up in the pharmaceutical industry. My family owned a wholesale pharmaceutical company, so I was familiar with how things worked there. I went into public health and later into law school. I then replaced a lawyer with a science background at the Tufts Study of Drug Development, that was about 15 years ago and I have been working here ever since.

RA: How would you summarise the key changes you have seen in drug development for pharma over the last 15 years?

CM: We are coming down to the fruition of stratified medicine, which started in the 80’s with orphan drugs. Back then there were treatments for smaller populations but the drugs, although expensive, were considered to be cost-effective because they prevented a loss of worker productivity and quality of life problems etc. I think the trend now is moving from drugs that address large populations – 15 or 20 million – down to treatments that address 1000s or 100s of patients. There are of course a lot of changes that go along with that. We are also heading towards being able to sub-divide patient populations into strata to identify the likely effectiveness of a particular drug for a particular patient, so-called personalized medicine.

“We can then look forward to a period of increasing productivity over the next decade.”

There is also a heavier emphasis on value, because who pays for drugs has changed. It used to be that two thirds of drugs were paid for privately in a lot of countries, now, even in the US, we are getting to the point where 40–50% of our drugs are paid for by the government. Very few drugs are now paid for by individual payers. That again has had an impact on what drugs are selected for treatment.

There has also been a paradigm shift in how we go about the process of research and development. Some have suggested that only about 20% of the drug pipeline now is in the hands of “big pharma” and some big biotechs whilst the other 80% is spread out over many companies. We have undertaken projects that seem to support that. We are looking at US industry–academia collaborations from 2008-2010 and we have found in just 20 states, almost 500 companies are involved with academic–industry collaborations.

Similarly, there are around 20–25 FDA approvals for new drugs per year. Over the past 5 years there have been 75 companies that have had a drug approved. The approvals are much more widely spread across companies than they used to be, which is probably a good thing in the long run.

RA: What do you consider to be the biggest challenges or risks facing innovation in drug development right now?

CM: One is the funding environment in terms of available funding. The big companies, to some degree, are sitting on funds, not knowing exactly where to go next. In addition, there is a change in the types of products we are targeting, and a growing trend towards targeting these more stratified patient populations.

We have also learnt a lot about biological mechanisms and disease pathophysiology, which raises more questions and more issues to resolve.

Furthermore, we are adapting to the paradigm change of a more open science approach. There is less control on the part of the big pharma companies and more players involved creating more issues.

There are a lot of changes going on that will be smoothed out eventually. We can then look forward to a period of increasing productivity over the next decade.

“There isn’t a lot going on right now in terms of FDA really exposing itself to the scrutiny of the public…”

RA: What impact do you see the transparency initiative having on collaboration and drug delivery?

CM: I can’t say that I see much of anything happening now except a lot of discussions to see what people think will happen.

What has been put forward seems to be more about what is making the information, coming into the FDA, more transparent to the public. There isn’t a lot going on right now in terms of FDA really exposing itself to the scrutiny of the public. That will probably happen because there has to be some give and take on this transparency initiative.

There will be more information out there, hopefully that will be of use. There are some concerns as we are already experiencing information overload and there are also concerns over who has the information and how they will use it. We are probably not going back so we have to just push forward. Informatics will become very important, as it has already in translational medicine. It will just be a matter of managing the information that comes out of this transparency project.

Our transparency initiative will also be of significance if it becomes a two-way street where the FDA really starts to talk about their decisions and why they make certain decisions. A lot can be learnt but there is this atmosphere of a little bit of chaos right now. Hopefully a concrete structure will emerge.

RA: What impact do you see the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act having in the long term for pharma and biotech?

CM: In the US although a federal law was passed we are seeing different reactions across different states. Some are embracing it and passing their own commensurate laws and programmes whilst others are fighting it. It’s going to be a while before this all straightens itself out.

There is anticipation that there will be a boost to R&amp,D in some areas. As far as biosimilar and the market exclusivity trade off it is hard to say. People are predicting a muted impact over the first 5 years in terms of biosimilars until they work out exactly what the tiering process is going to involve. You can’t just allow biosimilars out onto the market with the same sort of regime that you have with small molecule generics.

The other area is terms of value and the comparative effectiveness research initiative which is engrained in the PPACA and the attendant legislation. This will push forward the whole emphasis on comparative effectiveness to some degree. With increased comparative effectiveness research for market positioning, we will see more risk sharing deals, as well as new ways to prove the value to third-party payers.

“There may be certain therapy areas that are more problematic than others, such as opiods which could make companies shy away from them…”

RA: And finally, what impact have REMs had in the US and as a result what impact do you see this having on other markets such as Europe?

CM: Well most immediately there have been complaints in the US towards REMs in the US. One is that they emphasise risk much more than benefit, which has been scaring patients. They have a lot of things to work on in order to have the benefit in risk management that they had intended.

In the meantime it is interfering with the approval development process so they have to certainly improve and streamline that process. Some REM programmes can be quite expensive in terms of managing them over the life cycle of the drug which is adding to the regulatory burden and costs for drug development. There may be certain therapy areas that are more problematic than others, such as opiods which could make companies shy away from them, which could be a concern.

Certainly Europe may think there’s not a lot of benefit in a REMs programme, or they may think it’s good or better than their risk management programmes. It is a close call as to which way Europe will be heading in the future!

RA: Christopher, thank you for your time.

About the interviewee:

Formerly a practicing veterinarian, Dr. Milne later attended Johns Hopkins University where he earned a master’s degree in public health with a concentration in epidemiology and health statistics. For six years, he worked for the New Jersey Department of Health, initially as a researcher in health risk assessment, later in legislative and regulatory review as Manager of the Public Response Program, and finally as Emergency Response Coordinator. In 1998, Dr. Milne graduated from UNH Law School, where he studied environmental and health law, and is currently a licensed attorney.

Dr. Milne joined the Tufts Center for the Study of Drug Development (Tufts CSDD) in 1998 as a Senior Research Fellow in order to address legal and regulatory issues. His current research interests include: identifying and evaluating problems and solutions affecting innovation efficiency and the globalization of R&amp,D, tracking the progress of incentive programs for special patient populations and neglected diseases of the developing world, assessing the impact of emerging regulatory and reimbursement trends, such as risk evaluation and mitigation strategies (REMS), comparative-effectiveness, and risk-sharing arrangements with payers, and, tracking new developments in science and policy initiatives, such as FDA’s Regulatory Science Initiative, the EU’s Innovative Medicines Initiative, and Translational Medicine. Dr. Milne served on the journal editorial board and as chair for the annual meeting R&amp,D Strategies Track for the Drug Information Association during the 2000s. He is currently on the editorial board of the Food &amp, Drug Law Journal, an Honorary Fellow at the University of Edinburgh, and Associate Director of the Tufts CSDD.

What impact will REMs have on European markets?