Bringing drug discovery into focus

GSK’s Anne Phillips offers a clear picture of transparency, bringing benefits to patients and the challenges of carrying out clinical trials in a global environment.

“With Avandia and with any drug, the key was and is to be transparent. If you have data, get it out there, let people know it, understand it, query it, and that is what we had done”
-Anne Phillips

It is Anne Phillips’s background as a physician that led her to a patient orientated area of pharmaceuticals. As Medicine Development Leader at GlaxoSmithKline, Phillips works at the oncology group within Research and Development, overseeing the development of any one particular asset from the earlier preclinical development to managing it in different markets around the world.

“I am fortunate enough to oversee the aspects of the development of Eltrombopag, which is a drug that works to increase platelet count in patients who have low platelets and are predisposed to bleeding as a result of that. We currently are indicated for ITP in the US, and the job is really fantastic because it brings together all of the experience that I’ve had in pharma to date,” she explains.

So how has the transition from doctor to her recent appointment at GSK affected her management approach? Phillips advises that her role involves a multitude of management and leadership aspects as she oversees a huge number of individual projects.

“As a physician I have this very strong desire to add value to the lives of patients. So it doesn’t really matter what role I’ve had, that’s always been core to what’s important to me. This role is fantastic because the drug is very effective at increasing platelet count, and the patients who are at risk are really at risk of serious bleeding, so there’s a huge impact,” she continues. “In my view, ultimately, it all moves towards making a very important drug of great value, and available to patients who need it.”

Clinical challenges
Phillips entry into the pharma industry, specifically drug discovery, has come at a time of challenges. Modern drug delivery is now very different to the way it once was. She notes that even when proof of concept has been shown within a drug, conducting clinical trials themselves is a huge challenge to undertake in a global environment. “You have to make sure that you conduct the study in the right patients at the right dose and design the correct study. Sometimes the logistics in the global environment of getting subjects enrolled in the study can, in and of itself, be a big challenge.

“There are clear regulatory challenges, differences across the globe, once again, in regulatory requirements and what is needed there. The safety hurdle that we’re seeing for drug development is now unprecedented globally. That is a huge challenge – it’s a very risk-averse environment. You have to anticipate those potential challenges to any drug, and then once you do get approval, what the label looks like and how you can get that drug to the patients themselves. There’s the payer component: you can get a drug approved, but if you can’t get the payers to pay for it, the patients can’t get the drug.

“So that, again, is a huge challenge, and there is such a diversity of payers and requirements and what they need and don’t need from any particular drug. That is not a new piece, but it’s a new and more important challenge than ever right now. And you need to be able to solve that in order to get the drug available for patients who need it,” explains Phillips.

As Medicine Development Leader, Phillips has a small core team that works alongside her on an ongoing basis, with a number of broader teams that work to deliver the different aspects that feed into the core team. She has no direct reports – no direct managerial control over individuals – but does have control and input into annual bonuses. GSK’s structure ensures that its individuals report up through their lines, determining efficiency within the different processes of the drug’s development.

“I can choose the individuals to work on a particular project. You have to have an incredible team spirit, an incredible commitment to development of an asset to really run this kind of structure well,” she says.

Global challenges
GSK’s R&D centres are located around the globe, and so multi-site operations bring an even bigger possibility of challenges. “On the one hand, to have that available is fantastic,” says Phillips. “So you can get diversity of subjects enrolled in the clinical trial. Diversity in terms of input and expertise into how you develop an asset the best way can be incredibly beneficial. There’s wealth of patients around the world that you can access and get the drug to, so there are a lot of advantages. Time zones are often a problem – working on the east coast of the US and working with Japan and Australia makes both timing and language an issue.

“Very often in clinical trials some of the scales that we use may be validated in one language, but may be interpreted quite differently in another. As we have to have more and more health outcome measures, you have to make sure that what is important to somebody in the US is important to somebody in the country in which you’re conducting the clinical trial. Standards of medical care can be very different in different countries. Certain procedures may be routine in one country and not acceptable in another country.

“So there are a multitude of differences involved during regulatory approvals – you can get a trial up and running quite quickly in certain countries; it can take ten months to go through just approval to get a study started in other countries. So there are a lot of huge differences, but in the end to get the diversity of subjects into a clinical trial outweighs those challenges.”

Being part of a successful global brand does bring innate weight and advantages, however. The size of the company, number of contacts and knowing individuals in different parts of the world are just some of the benefits that Phillips points out. She notes the way in which other global companies operate, working through CROs to enjoy similar benefits.

But in the current pharma climate of major drug mergers and buyouts, how does this affect GSK and does it add to their list of challenges? GSK’s strategy has been to long-term install a very strong R&D group. Over a number of years, the company has been supplementing very strong scientific internal discovery engines with more externalisation, which has been conducted many ways. Phillips notes seed as an example of this.

“So this centre of excellence for external drug discovery is a very small group of individuals that has gone out over the past number of years to work with biotechs around the world, creating alliances with them to allow the biotechs who really have that very strong expertise in certain areas to develop their own pipelines in alliance with GSK.

“The idea is that we don’t get in and interfere and take over their assets they develop in a biotech way with their expertise to a proof of concept point, and at that juncture GSK can option that molecule. It’s a risk-sharing model, and it’s one where the biotech is incentivised by milestone payments along the way. So it’s a different kind of externalisation of drug discovery, and it’s a way to supplement what is going on internally. Now what we’re seeing is more and more of this activity – in the different centres of excellence for drug discovery they have an increasing proportion of their work – they’re continuing those programs that they’re excellent at internally.

“However, they’re also looking outside for individual assets that they might bring into GSK; on a bigger sense GSK is looking for smaller companies that we might want to acquire. Sirtris was an excellent example of a small biotech company that GSK recently purchased. There are a number of different innovative business models that we’re using and looking at around the globe to really supplement the core R&D work that’s ongoing. So there are a number of different strategies. Importantly, there’s a diversification of the way that we are going to feed that R&D pipeline.”

Personalised goal
Phillips’ own ultimate goal is not self-serving; her vision is to bring medicines of value to patients, and for her, 2009 is a year in which to be looking backwards, not forwards in terms of revolutionary therapies. “There’s a change in the focus now, and we are beginning to take a look backwards, in a sense. So we work from the patient to what we’re actually developing. It’s the end-user that will be changing the focus as to how drugs are going to be developed.

“What are the unmet medical needs? What is of real value to patients, to payers? What is that need, and then how do we develop molecules that will go there? Whereas previously we would focus a lot on developing as many molecules as we could. There was also a lot of ‘me toos’. The fast followers didn’t have to be terribly differentiated.

“It’s not going to be acceptable going forward. Each new medicine is going to have to demonstrated clear value before it will be reimbursed and before patients will be able to get access to them. So we’re going to have to start thinking very early on, “What are the characteristics that are going to make this medicine add that incremental value?” Just being a different new chemical entity doesn’t necessarily translate to value for the patient,” says Phillips.

She explains that forcing these changes also bring challenges, such as the death of blockbuster drugs and technological advances, as well as being able to meet individual needs of particular patients. She also notes the importance of generic competition: “If you have a patient with a medical condition, and you have three to five genericised medicines, in order to rationalise paying for a new drug, you have to have value over the generic medicines in order to justify paying a premium price for new entry into a particular therapeutic market.”

The pharmaceutical industry’s recent race towards super-fit manufacturing and supply chain was something blueprinted by the automotive and aerospace industry around 25 years ago, so why has it taken so long to get to this method? Phillips was quick to add that developing a drug has always been expensive – one out of ten molecules successfully becomes a drug – and the process has always been difficult.

“It’s even more difficult now,” she says. “My background isn’t in manufacturing, so I can’t speak specifics about what has happened in the past, what’s happening in the current environment or what is happening going forward, but certainly our manufacturing processes at GSK have always been not just extremely rigorous. Not only because they have to be creating medicines, but very rigorous in continuously improving and becoming leaner and focused.

“Ever since I’ve been in the industry I have seen that very clear drive towards becoming very lean, very effective and maintaining the highest possible standards.”

Safety scare
However, slowing down the successes within the pharma industry is the recent safety scare surrounding Avandia, which produced quite a wide impact throughout the industry. But, from Phillips’ perspective, the handling of the situation was nothing other than successful. She remarks on the transparency; “The meta-analyses that GSK had done had been given to the regulatory authorities many months before this became a big media issue, so there was certainly transparency there. The data had also been in the public domain on the clinical trials register, so it also had been available for a long period of time. What happened around Avandia became larger than life.

“It became a very big media issue, and patients reading the newspapers, listening to the television or listening to the radio became frightened, and it’s a difficult situation. I’m not sure that there could have been any more transparency because science was out there, but the all-important relationship between a physician and their patient is where we had some difficulty here.

“That relationship between physician and patient, for all medicines, is pivotal. It is unfortunate when any situation becomes a big media issue and people watching the media make their own personal decisions based on what they’re seeing rather than making sure they get the advice from their healthcare provider.”

Phillips explains how GSK worked hard to place the science in the public domain at that time, and published all of the date, but the difficulty remained with the attractiveness of a sound bite. It can be digested and incorporated, so the scientific explanation doesn’t lend itself as easily to a quick sound bite, and therefore a difficult message to get across. The key, for Phillips, is to “Continuously make sure that the science is in the public domain, is available to those who can understand it, digest it and then transmit it to patients and to the public in an appropriate way.

Lessons learned
“With Avandia and with any drug, the key was and is to be transparent. If you have data, get it out there, let people know it, understand it, query it, and that is what we had done. That clinical trial register – we had done that with the regulators. We had been in constant communication.

“It’s what is expected. As with Avandia, publication is critically important, not just to try to generate information, but it has to get into the public domain. So that’s done in different ways. It can be done by registers, publishing in journals, presenting at scientific conferences – there are different venues for doing this. But the key is to be very open and transparent about the scientific data.

“The lessons learned was around the impact of a sound bite or what an interpretation of data can do mean. But, you have to be rigorous about the science, you have to be rigorous about the safety profile of every drug, and you have to be always transparent about it.”

Anne Phillips is Medicine Development Leader for eltrombopag, a thrombopoetin receptor in the Oncology R&D Unit at GlaxoSmithKline.