Changing Times

Wyeth’s Thorir Bjornsson talks to NGP about dealing with attrition, the fallout from the merger with Pfizer, and what the future holds for the industry.

“The merger will create an extremely strong company capable of doing things even Pfizer wouldn’t necessarily have been able to do on its own”
-Thorir Bjornsson

The targets have been set. By refining the number of potential therapeutic targets analyzed and decreasing development times, R&D expenditures are expected to drop substantially. But how can the industry achieve this? Bjornsson advises that a number of industry challenges must first be addressed, from decreasing productivity to increasing guarantee costs.

“The most important issue affecting the industry, certainly from my perspective, is attrition. Attrition is very high and varies from company to company, from therapeutic area to therapeutic area, but by and large it’s about 90 to 95 percent. What this means is that the likelihood for success for any given new compound that comes into development is around 5 to 10 percent, which is terrifically important to keep in mind.

“That’s the baseline where we are today. Anything we try to do to increase productivity means we are up against this, so the question is how can we become more productive? Productivity overall is the underlying the solution to the challenges that we have today, and so the fundamental solution has to focus on a better understanding of compounds, a better understanding of the likelihood of success and how likely is it that that will become a positive outcome. We also need to ensure that safety issues are not going to become safety problems with our compounds.

“Similarly, it’s important to understand how the body handles the compounds, and when we do, then we can add up these different characteristics and if they all line up then our likelihood of success and thus productivity will increase drastically. So productivity is key: predicting the likelihood of what will happen and get the desired outcome,” says Bjornsson.

The subject of increasing productivity has always been high on the industry agenda. Historically, the approach to attrition within the pharmaceutical industry has varied from company to company. Wyeth’s approach is steered by the recent works with metrics instituted by former President of Research Robert Ruffalo when he joined the company in 2002.

“We set productivity metrics, meaning you get so many compounds per year that are put on the development track and so many R&Ds per year,” he explains. “Wyeth very recently tuned down the number of compounds going into development to a lower number. For us, the issue is always quality, and the ability to have compounds better characterized and therefore likely to succeed.”

Global challenges
Wyeth’s R&D centers are situated across the globe, and despite the obvious benefits of multinational operations, the challenges these centers face is increasing. Bjornsson notes the latest big trials and the problem of conducting them with the US and Western Europe, due to bigger regulatory requirements. Most major pharmaceutical companies now conduct many of their biggest trials in the emerging markets of China, India and the Far East, as well as in Eastern Europe were the number of hospitals is increasing.

“It brings increased challenges in terms of the monitoring of sites, due to some of their practices not being perhaps exactly the same as we are used to. Similarly, there are regulatory agencies in those countries that we have to work very closely with, and they become more cumbersome in a way. There are now more regulatory agencies involved, rather than the FDA or the individual regulatory agencies previously used in individual European countries.

“Also, the number required for such trials to get to a statistical outcome has led to an increased number of patients. With diseases also ever-changing, the process becomes more complicated, and again requires a higher number of patients than before.”

When asked if the days of so-called ‘easy wins’ for the big drug companies have come to an end, Bjornsson agrees. “I’ve been in this industry for a while and looking back, I’m not sure I would call it the good old days, but it is true, certainly for those where disease cases were easier to investigate. Studies were shorter; it would take a shorter time to see whether you had clinical effect or efficacy, and you would see the results much sooner.

“Nowadays, studies are much more complicated, and chronic diseases, such as Alzheimer’s, are now of key interest to the major drug companies. Some of the immunological diseases – arthritis, lupus and so on –only require a year maximum to see a meaningful clinical outcome.”

Mergers
The recent pharma buyouts are sure to only increase these challenges, as the bigger the operations, the bigger the challenges. The mergers – Pfizer/Wyeth, Roche/Genentech, Merck/Schering-Plough – met with a mixed reaction within the industry. For example, John Lechleiter, CEO of Eli Lilly, was dismissive: “I think we’re seeing deals that are really driven more by weakness than what I would describe as strong strategic combinations. They are predicated on synergies and massive cost cutting that will improve short-term problems but fail to answer the long-term question of research productivity.” So how is the focus on R&D retained during the merger and acquisition process to ensure Wyeth continues to combat these problems?

Bjornsson is quick to note that staff at Wyeth “are all extremely excited” about the planned acquisition. “It will create the world’s biggest pharmaceutical company and will build on the strengths of both companies. When you add those together you have a hugely diverse pharmaceutical company that crosses all platforms: small molecules, biopharmaceuticals, vaccines and then subsequently also the new avenues for development like nucleotides.

“That’s the view we have taken and we fully embrace the future as a part of Pfizer. The merger will create an extremely strong company capable of doing things even Pfizer wouldn’t necessarily have been able to do on its own.

“Granted, over the years there have been various criticisms, questions or people raising doubts about mergers and acquisitions in the pharmaceutical industry, and certainly, if you go back 20 years, you see how many companies have just disappeared. Prediction is always on a case-by-case basis, but as for this particular one that is facing us, we’re extremely positive and focused on the future and will be sure to make certain that people remain optimistic and focusing on the projects they have to work on today, because that will only make the future better for the combined company.”

To combat any disruption that the merger may cause, Bjornsson notes Wyeth’s strategy of focusing at local levels. He advises that by keeping individuals focused on their individual projects, the amount of disruption will be kept to a minimum. Aimultaneously on a higher level, plans are being formulated as to how the combined company will work.

Disease therapy
Bjornsson says it’s impossible to predict how the industry will develop in the future. “I wish I had the answer to that. There has been a lot of interest in bioinformatics to better understand biological pathways, to understand what pathways fit best with a given disease or a given indication. Similarly there has been a lot of interest both in the lay press and the scientific press about topics like personalized medicine.

“Those two are related. Our understanding of what causes a disease in one person or another may not be exactly the same on disease expression, but it looks very, very similar. So looking to the future, probably more than two decades, one does fully anticipate and hope that with increased scientific understanding, better systems biology and increased user technology, eventually we will progress to be able to address the most significant diseases,” he says.

“There is one thing we should never lose sight of. If you look back over the history of drug development, many of the big successes – such as cholesterol lowering, and the oncology diseases, like the Philadelphia chromosome that led to Gleevec – in both instances the scientific basis that led to those very successful therapies was due to medical knowledge that had been accumulating over five decades. So even though things are challenging and difficult, things usually become better and better. We also have to be patient; it takes time for science to move on and become evidence-based.”

One of the more infamous challenges within the pharmaceutical industry was the recent health scare regarding GSK’s Avandia. Bjornsson says that the pressure on the pharmaceutical industry is too much, and that responsibility should be placed on the national agencies, rather than leaving it to the drug firms to find every disease cure.

“We are all in this together. We all die at some time. We all have diseases. It is too much to expect that only the pharmaceutical industry will identify the challenges in the societies we have. The pharmaceutical industries certainly will do its part and has done so in the past. But pharmaceutical development is an extremely costly endeavor, and we need to have the room to be able to identify the future breakthrough drugs that will eventually come.

“Most of us in the pharmaceutical industry feel that some of the criticism that has been leveled against the industry is just not well-founded. The industry, through its various organizations, has tried to make its case, but it takes a lot of effort and some other mechanisms might be utilized to explain the value that the pharmaceutical industry has to society,” he adds.

But times are changing. The Obama administration has unveiled the preliminary details of its health-care reform plan and is displaying a commitment to provide wider access to generics, which is sure to have an impact on the pharmaceutical industry.

“We’ve only seen the broad strokes of what the new administration is thinking about so far, and in many respects it isn’t that different from what we saw in an administration one or two removed.

“From my own department we’re dealing with the earliest part of generic development, and I don’t see it impacting on that a whole lot, except we all have to be doing better and applying greater science to identify the best possible way the drugs can benefit those who need them and finding value-added medicines through better tests. Personally, it challenges us to do better from a pharmaceutical perspective. I’m not quite certain how that will all play out.

“I firmly believe that when there are challenges. We need to rise to them and the history of this country has proven we can do that. With the challenges come new solutions and we will typically do better at the end of the day.”

Thorir Bjornsson is Vice President of Early Development and Clinical Pharmacology at Wyeth. He joined Wyeth in 2001 from Bristol-Myers Squibb, where he was Vice President of Clinical Pharmacology and Experimental Medicine.