By Rob Wright, editor in chief, Life Science Leader
Last year’s acquisition of Genzyme by Sanofi was unusual, but probably not in a way you would expect. Once you look past the sheer magnitude of the acquisition (i.e. $20 billion+), you notice that, unlike many of the other companies acquired by the $48 billion- dollar behemoth, Genzyme continues to maintain its cultural identity. Indeed, instead of being assimilated into the Sanofi culture, Genzyme continues to maintain its own president and CEO in David Meeker, M.D., who previously served as Genzyme’s COO. That’s impressive considering Meeker is the only member on the Sanofi leadership team carrying the title of CEO other than Chris Viehbacher, CEO of Sanofi.
This move seems to indicate a desire to not only preserve the Genzyme culture, which Meeker describes as being highly purposedriven, but also to incorporate that into Sanofi’s revamped strategy. “It wasn’t that we had a brilliant strategy,” Meeker says about the Genzyme culture. “The disease areas where we work are so small that you cannot help but to come into close contact with the people who rely on and are benefiting from your drugs.” Though your company might not be in the business of discovering drugs for rare diseases, Genzyme’s forte, perhaps you can learn from some of Meeker’s insights as to Genzyme’s approach to rare diseases, why Sanofi decided to acquire the company, and how Genzyme is helping to transform Sanofi.
Acquiring A New R&D Footprint
In 2009, the decision was made that Sanofi would respond to the challenges posed by the pending patent cliff, generic competition, and cost-containment pressures from third-party payers and healthcare authorities by implementing a new strategy that would reposition the French-based pharmaceutical juggernaut for more stable and sustainable revenue earnings and growth. According to its annual report, the company needed to transition away from a reliance on blockbuster medicines and, instead, optimize its approach to R&D.
The first step in this process involved the reallocation of some of its internal infrastructure toward partnerships and collaborations. The second step involved redesigning its internal R&D footprint. For a company built on the backs of blockbuster drugs likes Ambien, Lovenox, and Plavix, this was no easy task. Remember, though, Viehbacher is a CPA with a decidedly business background, having started his career with PricewaterhouseCoopers. Meeker on the other hand, is a trained medical doctor, having practiced medicine at the world-renowned Cleveland Clinic for six years prior to joining Genzyme. Perhaps Viehbacher could help Genzyme with the business challenge surrounding its well-publicized production problems, while Meeker could help Sanofi continue to redesign aspects of its drug development approach.
The Genzyme Way
According to Meeker, the Genzyme way to drug development for rare diseases can be applied to drug discovery in general. “The general concept is that you are trying to solve a problem,” he states. “You have no chance of solving the problem, if you don’t thoroughly understand the problem.” In the case of rare diseases, there is often very little information, and what information there is often involves very few patients. In order to best understand the problem, you have to get close to the patient. One way of doing this is helping to create organizations to help connect patients and providers. For example, since 1991, Genzyme has worked closely with the international Gaucher community to understand the disease’s epidemiology, history, and long-term treatment outcomes, through the creation of the International Collaborative Gaucher Group (ICGG) Gaucher Registry. This organization includes more than 700 participating physicians, representing nearly 6,000 patients, with more than 40,000 patient-years of follow-up data, and has resulted in nearly 30 published papers on Gaucher’s disease. The Genzyme investment in this organization is estimated to be over $50 million since 1991.
Meeker sees healthcare as much more intimate than other industries. “It is not like purchasing a washing machine,” he states. If you are going to connect with and solve the problem a patient is experiencing, you need to care about that patient, and their problem. “I think failing to see these health problems as something you need to care about is often the gap between what defines success in development of innovative medicines,” he states. That’s why Meeker always seeks to include some healthcare providers for the Genzyme clinical and commercial teams who have had the opportunity to practice medicine, not just have a medical degree.
“When it comes to applying medical training to the individual patient,” he explains, “that is the art.” For Meeker, successful drug development is taking the understanding of medicine’s data-driven elements and combining these with the understanding of an individual patient, which gives you the best chance of getting the right answer for that specific patient. “You have to care about the people you treat or may be benefiting from your medication,” he states.
Genzyme’s culture has what Meeker describes as the patient-provider connection. “There is a remarkable level of connectivity throughout the organization with the people we are trying to help,” he explains. Some of this connectivity Meeker attributes to the natural consequence of working with rare diseases, involving such small numbers of patients that it would be difficult not to become well-connected to their problems. In addition to supporting and helping to found such resources as the ICGG Gaucher Registry, Genzyme has taken other proactive steps to create connectivity, such as bringing patients in to visit manufacturing plants to speak with employees who actually make the drug or having patients visit Genzyme offices throughout the world to share their story. “We are a global company with a culture that is no different if you are in China or Cambridge, MA,” Meeker attests. Genzyme is taking the cultural connectivity approach learned in discovering drugs for rare diseases and applying it to its emerging multiple sclerosis (MS) franchise. For example, for MS awareness day the company had advocacy organizations and patients come in to help employees better understand the symptoms and sensations the disease causes. Employees were given the opportunity to wear glasses, gloves, and macaroni-filled shoes, simulating the vision, numbness, and pain challenges patients with MS experience on a daily basis. These types of initiatives help to create a culture whereby employees are better able to understand people who have a need, are ill, reliant, and want to trust. For Meeker, trust is one of the key components in the healthcare equation to successful drug discovery.
Earning Trust Necessitates Being Trustworthy
At this year’s BIO International conference, Meeker conducted a presentation entitled “Orphan Disease Forum — Orphan Markets are Different: Are They At Risk?” During his talk, he described a recent visit to his own physician, asking audience members to recall their last trip to the doctor. He prompted them to think about sitting in the waiting room, being ushered back, getting weighed, measured, taken to a room, removing clothing, putting on a gown, and waiting some more. He then solicited responses from audience members as to how it made them feel. One person said, “Vulnerable,” while another replied, “Scared.” Meeker says, “You expect your car salesman to not necessarily be the most trustworthy individual. But that is okay, because you are prepared for that. In the healthcare setting, you are vulnerable. You are sick. You need help. You are scared. You need to trust.” Meeker is a proponent of creating an organization whereby employees not only understand their role as stakeholders, but as contributors. “In an equation that desperately needs to trust, we need to be trustworthy parts of this equation. You do that by saying, what is the problem? Who are we trying to help, and what is best for them?” To be a true partner in the healthcare equation, Meeker stresses the importance of working collaboratively with the patient, adopting a selfless approach, with no interest other than making sure the patient gets the best possible outcome.
Unfortunately, he sees this as something that sometimes gets lost in our industry. To avoid this happening in your organization, Meeker advises developing a healthcare mindset with the goal that every patient, with whatever disease, has a chance of being recognized, diagnosed, seen by an expert, and prescribed a therapy that is in their best interest. Meeker believes using these principles can be highly energizing to any organization because people can be motivated to do what they think is in the best interest of the patient. He cautions, however, “You have to bring something of value to the equation. This isn’t about going out and trying to ‘do good.’ You have to create value, and then you have to bring that value in a way that it can be understood and utilized with a thorough understanding of the potential benefits.”
The business model for Genzyme has always been to put the patient first, and the money will follow. Some have described this approach as taking the high road. However, Meeker believes that people gravitate to places like Genzyme because it is a comfortable place to work, not in the sense of being easy, but in terms of the philosophy. “People reading this and wanting to find out what the great secret is, already know it,” he contends. “Any company can usher patients into their organizations, hang their photos on the wall, and include the word patient in their mission statement. And that is great,” says Meeker. “However, the true definition of patient-centricity is an organization that will radically change its course based upon the input and evolving needs of the patient community they are there to serve. Unless you are willing to put the needs of the community first from an operational and business standpoint, then you are not patient-focused, and you do not have a sustainable model in rare diseases.”
Embracing The Acquired
Sanofi has certainly embraced the Genzyme acquisition. For example, in 2008, 61% of Sanofi’s sales originated from its top 15 products. In 2011, 65% of the company’s sales originated from six growth platforms and Genzyme:
But there is another benefit to the acquisition beyond sales. Sanofi is now the largest life sciences employer in greater Boston, one of the hotbeds for biotech R&D. Why Boston? According to Meeker, being in Boston is another component and the final key to developing the next breakthrough therapy. Consider this — the greater Boston area is home to around 190+ biotech-related businesses, world-class academic institutions including Harvard and MIT, as well as a number of highly ranked medical centers, such as Massachusetts General, Brigham and Women’s, and Boston Children’s. “You need to have cutting-edge internal science that is interacting with an incredibly networked external world of academics, small biotechs, and other places where innovation occurs,” he concludes. “It is not always easy to predict where it will be. If you are not out there looking and interacting with the community, you are going to miss it.” By connecting and interacting with the community, Genzyme has been very successful with its commercial drug development. How successful? Nearly half the medicines Genzyme markets have originated outside the organization — helping Sanofi to break free from the blockbuster model.
Embracing Advocacy Groups
Advocacy groups, charities, and research foundations have been playing an ever-increasing role in the drug discovery process. Many of these result from a family’s desperation to find a cure and, in the case of rare diseases, may lack organization. Genzyme CEO David Meeker says, “One of the most valuable things that we can do is to create communities to connect people. We need to connect patients with other patients and connect physicians who are interested in a disease with other physicians who might be interested in that same disease. What’s missing in these rare diseases is simply that community.” Meeker has seen the benefit of facilitating these connections in what he describes as the multiplier effect. “Things like disease awareness become much easier,” he affirms. “Communities enable research. They can support the creation of awareness. You can’t do the trial if you can’t find a patient.” Meeker even credits patient organizations with being extremely helpful in terms of gaining government support, not just in reimbursement, but helping to establish centers of excellence, establishing diagnostic testing, and newborn screening. “Virtually every aspect of development can be aided by the community,” he states.
According to Meeker, a number of rare disease organizations lack experience in knowing how to operate. But what they lack in experience, they make up for in determination and effort, making it fairly easy to partner with them. “As groups become larger, they often have professional management, who may or may not have a strong connection with the disease prior to joining the organization,” says Meeker. He believes the key is to remember the patient who desperately needs a cure and wants to trust that everything is being done to solve the problem.
Lack Of FDA Social Media Guidance
The FDA has yet to issue guidance for the pharmaceutical industry on how it can use social media, a key ingredient to the successful formation of patient advocacy groups. This is not a problem with which Meeker gets concerned. “When you have a small group of individuals trying to do the right thing, you don’t need a lot of rules,” he shares. “That has been the nature of the rare disease communities. In that setting, we are focused on sharing information. Our whole purpose has been to create awareness about the prevalence of the disease and the problems associated with it.” According to Meeker, the marketing of pharmaceuticals is becoming much more restrictive, and with that in mind, everybody in the healthcare equation needs to be much more attentive in trying to ensure that the patient/physician interaction is not manipulated.
Bringing Back Humanism To The Drug Approval Process
No one doubts that the people working at the FDA have a tough job. “It is truly one of those no-win jobs,” says Genzyme CEO David Meeker. “They have to ensure safety. Nobody rewards them for taking a risk.” Meeker believes safety is one of those things that is always hard to prove. “You might prove efficacy and safety in 100, 1,000, or 10,000 people, but the question, is it safe, always lingers,” he states. Meeker would like to see a level of humanism brought back to the regulatory drug approval process. He believes the FDA needs more support from society and Congress for the work it is trying to do. Further, he believes the FDA realizes that the organization needs to engage with the patient community, particularly in new areas. “They need to understand the problem to apply the risk/benefit judgment in an optimal way,” advises Meeker. “It isn’t that there is no risk, and it’s not that there is a perfect benefit. Weighing benefit and risk is the nature of the drug approval exercise.” Assessing risk and benefit is easier when working in an area where you have many therapies that have been approved previously, as there is a model with benchmarks and metrics from which to compare. But what if you are working in an area where there is no therapy or a totally different transformative therapy? In this case, you need the ability to think differently. “You need some context,” he affirms. “Context comes from understanding the patient and the problem.” According to Meeker, “Everybody wants the same thing, which is to make the patient better. If I am a payer, I have no interest in paying you more for the same outcome. Therefore, we as developers need to be clear about the value that we are delivering from our side.” So if you want to get humanism back into the drug approval process, the FDA, payers, and developers need to gain alignment on how best to achieve making people better — with acceptable risk — while being willing to think differently when a transformative therapy comes along. Take the 6-minute walk test, for example.
The 6-Minute Walk
The American Thoracic Society has issued guidelines for the 6-minute walk test (6MWT), considering it to be safer, easier to administer, better tolerated, and a better reflection of the activities of daily living than other walk tests. Regulatory bodies frequently use the 6-minute walk to assess a patient’s level of improvement when being administered an experimental drug. They also often use this test’s results as a criterion when considering approving a drug. Meeker believes the 6-minute walk to be an inadequate measure of improvement in many cases, and he thinks people need to entertain other options. “There is language within the regulatory framework — accelerated approval types of things — biomarkers — reasonably likely to predict clinical benefit — the whole question of validation,” he states. “It comes down to the disease itself and being open to new endpoints that are most meaningful to that particular disease. This requires a high level of disease knowledge on the part of the FDA, which means bringing in disease experts. It requires involvement of the patient community which, if it is a rare disease, may not have a significant amount of information at the time you are starting to develop the drug.” Meeker believes drug development companies, disease experts, and most importantly, patients, need to work collaboratively to help shape what a patient would view as clinically meaningful changes in their life. In rare diseases, it is not easy because the sample size may be as small as just one person.