Bold strategy has defined the year for Bristol-Myers Squibb’s Opdivo, boosting it into the lead position in the innovative immuno-oncology space. Launches in three key cancer arenas-melanoma, lung, and renal-have led to a unanimous selection for Pharm Exec’s Brand of the Year by our Editorial Advisory Board-and its run to clinical excellence may just be beginning.

	Nearly 18 inches of snow blanketed Washington D.C.’s Reagan National Airport on the weekend of January 23. Weather watchers throughout the district saw depths as high as three feet, clogging government functions, airports and businesses for the week. Despite a region-wide government office closing, FDA staffers endured and industriously managed to pump out an extremely rare Saturday approval.

	Usually when a PDUFA date, the deadline for the FDA to review a new drug, falls on a Saturday, the therapies are approved on the Friday before, but these were extenuating circumstances, explains Bristol-Myers Squibb’s Chris Boerner, head of the company’s US commercial operations. While the weather brought snowmen, hot cocoa and sledding to Capitol Hill, for BMS it was business as usual for an organization having a truly epic year; this was the 

 (nivolumab) since the first in advanced melanoma in December 2014, and the fourth for late-stage melanoma. BMS’s Princeton area offices were quieted by the squall Friday night into Saturday, leaving many employees homebound with their families. Some trudged through the white managing to make it in while others hunkered down with laptops and phones, conferencing in on demand to ensure they were available to handle the approval. Many others were holed up in far-flung hotels across the country, stranded by flight cancellations.

	FDA’s declaration granted an expanded indication for an immuno-oncology (IO) combo salvo, 

 (ipilimumab), against advanced melanoma. Now patients with unresectable or metastatic melanoma regardless of BRAF gene mutational status could be candidates for the dual treatment where BRAF V600 wild-type status had been a prerequisite, roughly 

 the patient pool for on-label treatment with the drug combo in metastatic melanoma.

	More so, BMS claimed one more victory in distancing its IO leadership position. And as the call for combinatorial attack plans in oncology gets louder, BMS can claim an early lead with a combo that uses its pair of therapies. Meanwhile, as a plurality of combination ideas are conceived and planned, whether they use two IO drugs, or an IO therapy paired to a targeted cancer drug, a fair share are likely to run through BMS.

	For launch team members, the blizzard was just another checkpoint and a minor inconvenience in an intense, emotional run that demanded solid planning, organization and passionate commitment. Schedules have been filled with positive data readouts, approvals and launches. “It’s been a roller coaster, launch followed by launch, and truly a once-in-a-lifetime career opportunity,” says Teresa Bitetti, head, US Oncology, BMS. She adds: “The commercial crew has been built upon a focus of getting innovation to patients, and emphasizing that patients should understand the new treatments options that are out there.”

	“We have certainly exploded the travel budget,” laughs Emmanuel Blin, BMS’s head of  worldwide commercialization. Seven approvals across three major oncology arenas, lung cancer, renal cancer and melanoma, proved an immense task for those on the commercial side, requiring a major investment and substantial planning. The audacity in planning such a launch could only be rivaled by the daring that it took to pursue so many indications along such a short timeline in the uncertain setting of clinical trials. 

 is batting a high percentage in these trials, and early data encouraged its medical leadership that their boldness was well founded. But for BMS, it was a confluence of factors, and overarching strategic realignment, that left the drugmaker prepared to pounce on the disruptive field of IO with a vision for answering unmet medical needs.

	The momentum carried by BMS’s PD-1 inhibitor 

 isn’t likely to let up any time soon. The company announced in January that it stopped its Phase III trial in head and neck cancer, CheckMate-141, early, on account of positive data demonstrating superior overall survival (OS) over the control arm, according to the study’s data monitoring committee. Overall survival 

 from this study showing benefit at one year was presented at the American Association for Cancer research in New Orleans in April. Head and neck cancer may see impressive 

 in the next decade, with IO products a major driver to the market. 

	Stepping back to a view of the overall IO therapies market, including BMS’s 

, its anti-CTLA-4 antibody; and Merck & Co.’s anti-PD-1 antibody 

 (pembrolizumab), the segment is projected for big numbers in the coming years. 

 put annual peak sales for IO in the upper $30 billion range within the next decade. IO sales in non-small cell lung cancer (NSCLS) alone project to around $10 billion yearly. Forecasters estimate 44% of the NSCLC market pie will go to BMS, while Merck will rein in close to a third of it. The time is ripe for companies to claim their positions in oncology, as IO therapies bring new promise and new profit potential.

	Dating back to 1990, BMS might have been considered the leading oncology company. “Those were the Taxol days,” explains Fouad Namouni, head of medical for BMS. But for some time, big Pharma was not all that interested in

 oncology in terms of driving revenue. During the early 2000s, for about a decade, BMS remained a player but might not have been considered the “leader.” However, throughout this time, the company was building something-a mindset, a spirit, to conquer cancer,  says Namouni. It was as if BMS was “hibernating,” waiting for the right time for a big move.

	BMS jumped on this opportunity in oncology when it 

 Medarex for $2.4 billion in July 2009. Though the deal would bring BMS both 

, as in all deals, it had its detractors, puzzled by the price tag and questions around the value of IO targets. Notably, 

of the transaction, given that it had a surer timeline and approval in sight.

	“We started talking to BMS on ipilimumab (

) as far back as 2000,” says Nils Lonberg, now  senior vice president, Oncology Discovery Biology, for BMS, and formerly scientific director at Medarex. “We established an early relationship with BMS, taking a leading position in the new IO field. BMS made a substantial bet in 2009 before the Phase III data was known. This could only have happened with a good understanding of the basic science of IO.” Lonberg 

adds that Medarex had shopped for additional buyers to no avail. “BMS was way ahead in thinking about IO when it decided to acquire Medarex. It continues to show its commitment to IO, with a focus that is integrated throughout the company.”

	Lonberg’s postdoctoral work at Memorial Sloan Kettering, which eventually led him to GenPharm, bought by Medarex in 1997, was focused on the genetic engineering of mice. This work led to the development of a drug discovery platform that has had a key role in the discovery of an impressive who’s who of antibodies-nine of which are either approved or submitted therapeutics: golimumab, ustekinumab, ofatumumab, canakinumab, ipilimumab, nivolumab, secukinumab, daratumumab, and bezlotoxumab. Medarex was involved in a substantial amount of partnering on this technology with many groups across the industry. 

	A key collaboration, initiated in 1998, that led to the discovery of 

 involved Lonberg’s team at Medarex together with Alan Korman at another biotech, Nexstar Pharmaceuticals (Korman joined Medarex in 2000, and is now vice president, IO discovery, at BMS), and Jim Allison at the University of California, Berkeley. Allison has since received plaudits (hinting at the likelihood of a Nobel Prize in his future) for his role in shaping this new vision in oncology treatment, and the partnership launched the Medarex team to the top of IO in its infancy.

	The preclinical data was strong enough for a run in the clinic with Medarex beginning Phase I work on ipilimumab in 

. The 2003 partnership with BMS fueled Medarex to persist until the buyout a half a decade later. “I was blown away by the commitment BMS gave,” says Lonberg, adding that it would have been difficult to persist in the long process of developing 

	“Training as a basic scientist is humbling. Not all ideas succeed, and it makes you have a real respect for nature-understanding its complexities and mysteries, and that you don’t understand it all,” Lonberg observes. “You grow up in the sciences with an almost Pavlovian response to data.” 

	It was with this data-thirsty mindset that Lonberg and his Medarex team stepped into the new field of IO. “There was so much new and exciting research coming from the interface of the immune system and cancer,” 

says Lonberg. The revolution in thinking of ways to approach cancer moved researchers from thinking about cellular mechanisms-how cells ultimately misbehave and become cancerous-toward thinking about how the immune system perceives these misbehaving cells. Of course, adding the immune system brings another layer of complexity, notes Lonberg. But the successes of IO therapies in the clinic, grasping some of this complexity, has been resounding in unleashing patients’ own immune systems to attack tumors.

	Fortunately, combining Medarex and BMS was not overly complex. In addition to the ongoing partnership, scientists at BMS had discovered the ligand for CTLA4, “so there was a natural intellectual fit,” says Lonberg. 

	Though the IO field was in its infancy, thanks to this high level of intellectual familiarity, BMS brass had a grasp of the field’s potential. Management realized the asset they now were holding. Clinical development teams ramped into high gear. 

	“I was asked to lead, and in early 2011, we kicked off the development team,” says Namouni, who had seen early melanoma and renal cancer data and was impressed but not blown away. Other IO therapies were showing potential in these areas, so positive results were not earth shattering. But what Namouni saw as unprecedented-the lung cancer data; IO had yet to display substantial results in lung cancer, so if this  could be confirmed, it could be transformational, he thought.

 was shrinking tumors, we knew we can impact survival,” says Namouni. He connected this real impact in survival for lung cancer to what he saw as BMS’s mission in its cancer comeback. “We made a connection to what we wanted to do to affect cancer survival, and we did it differently than most pharmaceuticals companies would have done. We did it in a bold way.” Investing at historic levels, an unheard of commitment, BMS set out after multiple tumor types condensed to an aggressively short timeframe. Given the scale of the effort, “we got looks throughout the industry,” says Namouni. “It was heresy to some degree to go for so many tumor types.”

	The BMS teams were inspired by the approach. This hypothesis that putting pressure on the tumor over time will lead to OS was proving correct. And with that in mind, teams wanted to move quickly for patients. It was easy to justify the extensive investments into the numerous cancer types, notes Namouni.

	The timing was perfect, too, for BMS’s leadership. BMS corporate strategy was transitioning from a diversified approach to one with a focus on areas of high need with the potential to bring transformational medicine. So the ingredients were there; the stars aligned to make that investment decision possible, explains Namouni. 

	Analysts had their questions regarding the approach, but company stock never suffered dramatically. Once people started seeing the data, critics were mostly quieted. Change is never easy, but the ingredients, culture and timing all came together for BMS to move forward with its bold approach. By 2016, 

 can almost taste entry into its fourth cancer type, and the aggressive trials have produced data that put the drug ahead of its competition. 

BMS held a key advantage in developing its anti-PD-1, which helps explain the lead it has taken over Merck’s 

. There is not yet a lot of data to make comparisons to 

 across indications in which it has provided solid survival data. But BMS added valuable experience from the development of 

. “We learned a lot about trial design and doing clinical development in the IO space. That was a major advantage that helped us expedite 

’s development,” says Namouni. BMS knew the optimal timing for peeking at data in an IO trial, for example, which gave the company a leg up, and other groups are still trying to figure out how to run their Phase III trials.

 to the market in advanced melanoma, with approval in September 2014. 

 followed soon after in December of that year. But it was 

’s first-place finish in advanced (metastatic) squamous NSCLC by six months that pushed it well ahead of 

	The industry’s emphasis on rare diseases, and the profits that can be found in these marginalized patient groups, carries a clear message into oncology. Where it’s evident that each patient is unique, individual tumors themselves can even be broken into sub, sub categories. A 

 mandate from the US’s chief executive branch with precision medicine terminology surely offers optimism that in the future, cancer treatment will be preceded by, and fitted to, in-depth diagnostics.

 its market thus far by discarding the shackles of personalized care and the complex diagnostics that come with it. What does it mean for the movement toward personalized medicine when the year’s biggest drug launched more quickly, and to larger pools of patients by making its personalizing diagnostic tests a companion, but not a requirement for treatment?

 has been a game-changer,” says Dr. Jeffrey Schneider of Winthrop-University Hospital’s Long Island Cancer Center, who treats lung cancer patients. Schneider says that as many as 20% of metastatic lung cancer patients, who would have been given little more than survival timelines in increments of six months, a year, etc., can now see meaningful responses and real survival with no known expiration date. He adds that though one in five see this response, the drug offers hope for five out of five. Before 

, there was such a “defeatist” mindset. In time, the remaining 80% will have other options rather than losing time and money on failing with a single IO therapy.

	Patients in the future will have better diagnostics that point them to another treatment, or an ideal combination of drugs. Part of the predictive diagnosis will likely include the presence of ligand PD-L1, which Merck included in 

’s trials as an enrollment condition, and as a result landed on its label. BMS also ran the trial looking at PD-L1, but didn’t use it as a criterion.

	The PD-L1 test does predict response, but not perfectly, explains Schneider. Roughly 44% of patients who test positive for the test respond well to 

, but about 5% of PD-L1 negative patients still see a response. With no additional tests to predict response, Schneider sees it as clearly worth it to treat these patients who are negative for the ligand. Payers, patients and regulators are also in line with the 5% gambit, given the hope of prolonged survival.

	The aggressive launch strategy has not been limited to the US. 

 is approved in over 50 countries, with reimbursement in at least one indication in each, according to Blin. BMS is seeing 

 attain similar levels of uptake and dominant market share across regions. The quality of the product is clearly first and foremost, but Blin also credits commercial strategies. “It’s a very competitive market, so it’s about not being complacent and remaining on our toes,” he says. 

	BMS decided on a unique commercial model for its global strategy that has been key in its rapid execution of commercial strategy across markets. “In most companies, you do the job twice-building a global strategy, then again for each

 local market,” says Blin. Because the company stressed speed to market, BMS strategized around regional market blueprints to be executed in each country rather than planning for each individually. “With new indications coming online at a rapid pace, we can’t spend time aligning behind each one.”

	In terms of access, companies typically negotiate for weeks and months in each country level to decide on local reimbursement. For 

, BMS “reverse engineered” the process prior to approval, building in bookend values that consistently brought results. The company has been able to bring organizational speed, mobilizing with the mindset that “patients can’t wait.” Blin adds, “As a commercial person, you don’t have the opportunity to launch a drug like this very often. When we started to see the speed FDA was willing to move at, the speed at which doctors were willing to prescribe, it became evident that we had something unusual. We had to build a commercial model fit to purpose. It’s a heavy investment but worth it when you believe you have something transformational.”

	“In the spirit of speed to patients, we knew that there is no regulatory way in Europe to have multiple indications submitted and approved at the same time,” says Namouni. It’s a sequential process whereby a marketing authorization application (MAA) is followed by a type-II variation and so on. In collaboration with the Committee for Medicinal Products for Human Use (CHMP) and the European Medicines Agency (EMA), BMS came to Europe with a strategy that was unique and perhaps an innovation in itself.

	The company strategized to use parallel submissions using different trade names, 

 and nivolumab MAAs for advanced melanoma and squamous NSCLC, respectively. EMA okayed the plan to “reconcile” the MAAs into a single marketing authorization under the trade name 

 toward the end 2015, “in order to accelerate availability of nivolumab for healthcare professionals in both indications,” stated a July 2015 press release.

	American consumers faced, and may have had difficulty avoiding, the boldness of BMS’s reported $42 million DTC campaign. As DTC inspires those across the spectrum, critics came forward with valid concerns that the “wide optimism” and a somewhat 

 message that patients might “significantly increases the chance of living longer” might have negative effects. And, of course, with greater exposure comes more voices hitting notes on the drug pricing debate, sure to 

’s more than $100,000-a-year price tag.

	“Diagnosis for the worst-off lung cancer patients basically has meant a referral to palliative care,” notes Bitetti. “There has been nothing new for years, so there was a nihilistic attitude in the doctor and patient communities.” 

	“The decision to do DTC in this space was not taken lightly,” adds Boerner. But BMS executives were quick to point to lung cancer as a truly unique situation. “Twenty-five to 35% of patients with advanced lung cancer are out of the treatment algorithm,” says Boerner. “So as much as anything, DTC was an effort to reach them.” BMS went down the DTC avenue because the company thought it was a “public health issue,” according to Blin. 

	DTC marketing and the widely reported news of former President Jimmy Carter’s successfully treatment for metastatic melanoma with 

 have certainly raised awareness, added Dr. David Spigel, chief scientific officer and director, lung cancer research program, at Sarah Cannon Research Institute in Nashville, Tenn. 

	Lung cancer is a disease area that has not seen data improving OS in many years. Thus the level of DTC investment makes sense, says Boerner. “There are critics who will always be negative on DTC, but patient advocacy groups were among those pushing us to do DTC and raise awareness.”

	The commitment to patient support and access to 

 is first in class, says Boener, noting the clear proof of this has been the positive reaction of payers. This is especially notable given the high list price tag for 

 and the environment over the last few years in which payers have been more than willing to wield influence, competition and the media against drugmakers.

	But oncology products are rather protected from the price debate because of the emotional quotient (EQ) involved in treating cancer, according to Roger Longman, CEO of Real Endpoints, a start-up focused on pharmaceutical reimbursement. Because of the EQ, payers feel that they have very little freedom to restrict use of these drugs. This could be changing, Longman believes.

 is certainly worthy of Brand of the Year praise, but unlike Humira, which might have gained Brand of the Decade status, anything that is true today is unlikely to be true tomorrow, suggests Longman. There will be competitors, and payers will look hard to competitors for superior value offerings. In a reference to tools such as DrugAbacus.org, which Real Endpoints constructed with Dr. Peter Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering, value measures and objective tools will become increasingly important for payers. Given other IO drugs coming to the market, non-IO agents, and the plurality of combinations that may be possible in the near future, there will be choices, and payers will be structuring ways of making decisions in a very complex market place, says Longman.

	In a year that saw some pretty unimpressive launches (see the PCSK9 launches), “we’re seeing that pharma has failed to recognize and make adjustments to see value, not from their internal angle, but from the external vantage point in a world dominated by institutional buyers,” explains Longman. Oncology launches remain impressive but given the greater competition, and the dilemmas around combos, the ability for cancer drugs to launch so impressively may change, too. Oncology could see greater impact from payers’ ability to manage out high prices, adds Longman.

	In regards to paying for innovation, BMS’s Namouni stresses that considering the impressive survival results showcased by 

 publications, it must be recognized that oncology treatment is witnessing a revolution. “Just look at the number of

. Not everyone realizes the impact this drug and other IO agents will have for cancer treatment. This creates great value for society and the overall economy.”

	For Dr. Spigel, a heartening moment occurred when one patient commented that his waiting room didn’t seem to be full of sick people anymore due in part to the effectiveness and fewer side effects with immunotherapies compared to traditional cancer drugs. Years ago, those awaiting treatment were in serious, and frequent, need of fluids and assistance. The perceived difference, Spigel notes, is telling for both outcomes and the outlook at the clinic.

	“Valuing this kind of innovation is the right thing to do, because we need more innovation,” says Namouni. “The journey is not finished.”

’s Senior Editor. He can be reached at 

Articles

Features

Pharm Exec’s 10th annual Brand of the Year is Bristol-Myers Squibb’s Opdivo, which has raced into the lead position in the treatment-shifting immuno-oncology space behind launches in three key cancers-melanoma, lung, and renal.

2016 Brand of the Year: Cancer Standout Opdivo

Pharm Exec sits down with industry veteran Jack Bailey, who discusses his onboarding strategy as new president of GlaxoSmithKline’s US Pharmaceuticals business along with the progress of GSK’s novel-and often controversial-approaches to sales force compensation and transparency in information disclosure. 

Everyone’s career trajectory is a mosaic of professional experiences reinforced by personal relationships, culture, and background. Can you identify the cumulative forces that shaped your career and brought you to your present position as president of GSK’s US pharmaceutical operations?

 It was family that led me into healthcare. My mother was an ICU nurse. I recall her very emotional experiences in caring for sick people. It also served as a preview of the issues confronting the health sector today, especially in the resource demands on our system of care. My father became a commercial 

airline pilot after military service, and in that role he worked for an industry with a safety culture committed to never making the same error twice. Compare that to healthcare, where it still takes, on average, 17 years to institutionalize a simple clinical practice guideline. I learned from my father’s business that patients don’t have to settle for persistent lapses in quality and safety, at high cost.    

	All this led me to embrace science in my undergraduate years, majoring in biology with a focus on genetics. I spent a year working in a research laboratory, but eventually realized it was the business part of science that interested me. That led to an MBA degree, which, in turn, persuaded me to seek employment in a pharmaceuticals company with a strong management training track. That company turned out to be Eli Lilly, where I spent the first 18 years of my career. 

	A transformational experience for me was serving as country manager for Lilly’s business in South Africa. The country was on the frontline of a public assault on manufacturers of HIV medicines, clarifying the reputational and access challenges uniquely associated with our industry. It was a defining moment for innovative R&D producers. I was fortunate to be exposed to it, providing lessons on how to engage as an effective advocate of policy that guides my work today. In addition, Lilly at the time was participating in a local joint venture with Glaxo, so I was able to gain exposure to what eventually became GSK.  

 How would you compare the cultures of the two companies?   

 The culture and values are similar, but the difference I see with GSK is a greater willingness to experiment-push the envelope-in changing the business model. Examples where GSK is leading the industry are our commitment to transparency in clinical trial results; eliminating physician payments; and our new commercial model that puts the patient interest first. These were seen as game-changers at the time. We now think the rest of big Pharma is moving in our direction.  

You assumed the top US job in GSK pharmaceuticals in February 2015. What agenda did you set for your 5,000 colleagues during those mission-critical first 100 days?  

 My principal objective was to keep the focus on our strengths as a business. A transition in leadership always creates some uncertainty. I thought it was necessary to maintain continuity with initiatives begun under the previous regime. There was a lot of good to build on.

	But it was also true that the organization had been undergoing significant change well before I took on the top job. Change can be unsettling to many colleagues, so it was doubly important that I kept explaining the initiatives underway. I wanted to be very clear that no one was traveling alone and that it was important we were all together in terms of the direction GSK was taking.  

	Even though I had a high profile, having managed two of the four business units here in the US, I resolved to make myself very visible. I spent much of the first 100 days listening to colleagues in small group settings. The goal was to engage colleagues on two levels: the head and the heart.  

	One fact became evident very quickly. GSK had strengths-but there was also stress. In a relatively short period of time, GSK had supervised the launch of eight products in the US. Deploying so many new assets put a lot of strain on

 the capabilities of the organization. We had a resources problem. The message I wanted to convey is that, while there would undoubtedly be more changes to cope with, the approach would be more fully aligned and inclusive of the rank and file. That, in turn, required more candor-highlighting not just the good news but what is not going well, too.  

	Finally, I spent time putting together my new leadership team. I sought more balance in the group, combining those with deep experience in the US marketplace with people with a more global perspective. 

 Your leadership of GSK’s US operations has coincided with a major transition in the local market environment for biopharmaceuticals. How do you explain to senior management in London what’s going on here in the US? 

 The simple message to HQ is the US market defies conventional thinking. It is not only big and complex; it is experiencing an unprecedented rate of change. We spend 18% of GDP-$3 trillion a year-on healthcare in this country, an amount equivalent to the GDP of France. Imagine such a cycle of “creative destruction” being imposed on the entire economy of a country of that size. It’s a daunting analogy to the radical disruptions unfolding here.

	I’d also say that healthcare in the US cannot be categorized cleanly or simply. It’s not a free market, nor is it a single-payer system run by government. Instead it’s a hybrid, organized around a diversity of approaches drawing from both the public and private sectors.  

	The 2010 Affordable Care Act (ACA) includes many provisions around expanded access along with new service intermediaries like accountable care organizations. There are approximately 5,000 full-service hospitals, 1,200 insurers, and a shrinking number of payers. If you are a military veteran, active or retired; low-income; age 65 or older; if you are employed or self-employed-each of these groups have different routes into a very complex system. 

	Pressure on our business is shaped by the harsh realities of demographics and costs. Suppliers and payers must generate more value from every dollar spent on healthcare. Consolidation, integration, and accountability are combining to redirect funding streams and, with it, the face of our customers. Physicians no longer stand alone at the top of the payment hierarchy. Pharmacy benefit managers (PBMs) are limiting what physicians can prescribe through increasingly restrictive formularies. 

	Pharma companies have been slow to adapt to these new dynamics. It’s a work in progress. We take the view that a proactive approach to market change can improve our understanding of the customer base and differentiate us from the competition. GSK’s senior management has encouraged our efforts to build a new commercial model to do precisely that.

What actions are required from big Pharma to address this new customer base? 

 We have to provide more value to the customer than we have historically, whether directly from our clinical offerings or from added financial information and services. The bottom line is you have to deliver to a higher standard of performance. The second element in dealing with the customer is increasing our engagement with them. We must elicit more trust. That involves being transparent about our business, to strive for the highest ethical standards, and putting the patient interest at the center of everything we do. Our aim is to institutionalize these rules of engagement in GSK’s new commercial model. 

Can you summarize the main elements of this new commercial model?

 It begins with an awareness that everyone is seeking to redefine-and reassert-their role in the healthcare system. We reach out to anyone with a meaningful contribution to make in how our medicines are used and paid for-value is set by the voice of the customer. This entails finding better ways to communicate with each customer. Is it still best to connect person-to-person, or embrace the digital and online multichannel platforms where many customers now prefer to get their information?   

	Another element is upgrading the evidence to demonstrate the clinical merits of a drug in addressing an unmet medical need. Our ability to do that has expanded significantly in the last decade, especially with the closer alignment of R&D with the commercial side at a very early stage of development. Along with evidence is a value-based approach to pricing. GSK was an early adopter of this concept, which we began applying globally back in 2010. In fact, if you look at our last six launches, all were priced at or below pricing for the existing standard-of-care products we seek to displace. Overall, on the basis of comparative industry measures of annual price increases, GSK products ranked in the lowest quartile  for each of the past five years.   

Can you provide a status update on the salesforce compensation realignment put in place four years ago by your predecessor Deidre Connolly? Any second thoughts about the execution?  

 Changing incentives for our sales professionals was a central feature of a company-wide initiative-the trust agenda-which also included a commitment to transparency in clinical trials and ending payments for external speakers to talk about our products. But it was not just about building trust. It was to be more in step with society’s expectations. What we did was significant, removing the prospective, volume-driven numerical sales target that most of the industry operates on in favor of incentives based on the quality of the interaction with a healthcare provider. The salesforce incentive is aligned with the provider interest in doing what is right for their patients.  

	Change is never easy; it was a bumpy ride, at first. We have addressed it through consistent, open exchanges with sales staff to identify ways to improve. Over the past year, the incentive system has been simplified and, if you talk to our people, you will find perceptions on both sides of the sales transaction have changed. Specifically, GSK colleagues now see that the rules actually provide them with greater access to healthcare providers, who recognize the value in ensuring their time with us is spent productively-on the clinical aspects of our therapies, and how to make them work for patients.

	But the bottom line is obviously GSK’s commercial performance, and here I can point to measurable results. For example, our new once-a-day drug, Breo, stands out as the seventh best out of 100 primary care products launched in the US in the last several years. On the HIV front, the two drugs from our ViiV unit, Triumeq and Tivicay, had two of the strongest launches ever in this space. And GSK has gone from having a low rating from physician groups on customer value to status as “most trusted” in the entire industry. That’s with the new incentive model. While I can appreciate what some of our competitors say, the facts show that being in step with where society and the markets are going, as we are, can be done without ceding the  ability to make the sale to customers.       

 How is GSK’s commercial model able to address a key concern for patients today-the larger share they must pay out-of-pocket for the cost of  medicines, even for relatively generous plans offered by employers? Surveys indicate this is fueling much of the public opposition to industry pricing. 

 GSK has a strong commitment to expanding access to our drugs. Innovation that sits on the shelf, beyond the reach of the patient, is no benefit to us. The fact that the ACA has increased coverage is a step forward-the law, which we supported when it came before Congress in 2010, was an important driver behind our move to this new commercial model.  

	That said, more must be done to facilitate access to medicines. GSK is committed to working with stakeholders to expand drug coverage and move access to healthcare to a better place. We have credibility in the debate due to early decisions taken by CEO Andrew Witty a decade ago to make information on our clinical trials transparent, so that any researcher could use it to form their own conclusions about our medicines. GSK also released more than 1,200 patents to allow NGOs, patients, and the public a chance to access therapies in areas where we lacked the resources or the therapeutic focus to pursue them. Our latest action in the access space is a comprehensive package of measures we announced on March 31 that includes forgoing patent filings in least-developed countries; licensing and manufacture of generic versions of our medicines in lower middle-income countries; committing our future oncology products to participation in Unitaid’s Medicines Patent Pool; and making information on GSK’s patent portfolio freely available to all. 

	Another example is the GSK Patient First program, which removed the incentive for our sales professionals to meet volume-based sales targets instead of pursuing the best possible clinical option for the provider and the patient. Likewise, GSK is the first pharma major to stop payments to external speakers to cite or promote our products at medical conferences. Feedback so far has been positive.  

	These initiatives set a precedent separate of any industry-wide consensus. We have chosen to drive change through our own organization first. But as the larger world outside struggles with the challenges of access and transparent behavior, we intend to be involved in that discussion, too. The stakes are so high-because the scientific potential is so great. It’s enormously exciting to me to see how in so many therapeutic areas our scientists are talking about cures and the full-scale eradication of disease. It raises the stakes in the effort to get to where we all want to be in making the healthcare system more open and accessible to patients who need those cures.  

The problem here is that other stakeholders now exercise significant market power in driving the terms on how patients obtain access to your medicines. GSK has experienced this directly with the PBM business-Express Scripts effectively removed access to Advair for millions of US patients when it removed the drug from its controlled member formulary several years ago. What was GSK’s strategy to counter that decision and keep patients on therapy?

 We have a long history of negotiating with Express Scripts, and with CVS Caremark as well. Like other pharmaceutical companies, we engage on an individualized basis and work very hard to find areas of mutual agreement. It’s not always possible, however, which partly explains why we fall short of our goal of full patient access to our medicines. We made our position clear to Express Scripts; despite that, the negotiations had an outcome we felt did not recognize Advair’s category leadership and many years of trust that physicians and patients had in the brand. Nevertheless, we chose to stay engaged with the PBM and eventually that allowed us to get back in the game. Today, virtually our entire product portfolio is available through the PBM formularies.

 Perseverance counts, especially in committing to an ongoing relationship, one that limits the possibility of sudden surprises. You also must be accepting of market realities. To expect payers to reimburse every product is naïve. It’s no longer a realistic business model for them. In response, pharma companies must align their case around the patient interest. For example, in the respiratory segment, where GSK has a dominant position, we emphasize the importance of avoiding market disruptions that compromise quality care for patients. This is critical, because low rates of adherence to therapy are a key vulnerability in the respiratory space, resulting in more sickness and the costs that accompany it. 

	Another reality is that not all payers are in the same place in terms of capabilities to track a drug listing decision to superior health outcomes. Performance on this score is variable. It’s messy. GSK is fully committed to helping payers create access solutions that move the patient experience to a better place. Despite so much progress on innovation, to the point of curing conditions that were once chronic or incurable, the financing and delivery model is still evolving. And the cost of such innovation has stayed remarkably stable for decades, at little more than 10% of the total spend for healthcare. It proves that innovation largely pays for itself.

How are you organized internally to promote the payer and patient perspective in securing access to GSK products?

 Our relationship with the patient and payer is at the center of the changes we’ve made to the organization over the past several years. R&D is now organized into Discovery Performance Units with clear benchmarks that require that the “voice of the customer” be weighed before moving compounds forward to registration. In addition, GSK has established a process called Medicines Vision that determines what evidentiary needs are required to convince payers to access our products. Frankly, it’s a tough culling process designed to separate the innovations that we might love-but the market won’t.  

What excites you most about the innovative science behind the treatment of respiratory ailments? What kind of progress can we anticipate in the fight against these diseases? 

 Patients have more options in addressing severe asthma and COPD. We now have an array of products that allow health providers to manage virtually every aspect of the condition, starting with monotherapy and moving on to dual and triple therapy as well as the various sub-types like severe asthma, which is the approved indication for our latest launch drug, Nucala. As the medicines get better, we are seeing higher rates of adherence among respiratory patients, a segment which has traditionally been among the least compliant to therapy. One benefit we have documented with Nucala is that the 5% of the respiratory disease population with severe asthma account for fully half of the cost of respiratory hospitalizations in the US. We are five months into the launch of Nucala and it is performing above expectations. So our science is definitely filling an unmet medical need, which is what innovation is supposed to do. 

 Do you anticipate additional product launches this year? 

 2016 will be a year focused on execution around our existing portfolio, now that the $20 billion asset swap with Novartis is complete. It’s no exaggeration to say the transaction has had the biggest transformative impact on GSK since the company emerged in its present form in 2000. With the work on that behind us, we build in more support for the 2015 rollout of Bexsero, a vaccine for serogroup B meningitis that we inherited from Novartis and now carries an impressive global franchise. We are also focusing on Nucala, for severe asthma, which launched here only in December but is experiencing stronger than expected market take-up. Finally, we are setting the stage for FDA review of a new subcutaneous delivery platform for Benlysta, an advanced biologic available via infusion since 2011 for US patients with lupus.   Assuming approval, this new platform should assure Benlysta’s status as a game-changing treatment.

Industry analysts are excited about the commercial potential of a new wave of biologics for respiratory diseases. GSK is the acknowledged leader in this space. How will you address pricing issues in this segment, given that most respiratory ailments are chronic and payers are used to paying less for treatments?  

 New therapies bring with them new approaches to managing the cost of disease. GSK now has a full suite of treatments to address virtually every aspect of respiratory disease, at every stage of a patient’s journey. Our message is that this will translate back into efficiencies and improved outcomes for patients, savings that can be applied back in the larger system, like hospital costs. Increased adherence to therapy is another example where we can engage productively with payers in cost-effective management of respiratory disease, in all its manifestations.   

What about the operations cost savings promised under the asset switch deal with Novartis? Is the £3 billion target promised over three years on track?   

 We have set clear synergy targets for the integration and we are on schedule to meet them. I can say we have already met the targets set for the US pharmaceuticals business, but the global businesses will continue to execute on both the consumer products and vaccines front. 

What about new research partnerships: any that strike you as significant? 

 Our Avalon venture in San Diego looks very promising. The multi-stakeholder partnership we agreed last year with the University of North Carolina Chapel Hill and Qura Therapeutics is committed to an audacious goal: finding a cure for HIV. It is mobilizing leaders in both the public and private sector to explore a wide variety of research leads, without silos or pre-conditions. The ViiV partnership with Shionogi and Pfizer is a historic accord that has proven to be both unique and commercially lucrative.  

	GSK is equally proud of our in-house research. Significant contributions to the clinical development programs for a number of our respiratory products were made by our Research Triangle Park R&D teams. 

What are three major goals that will guide and measure your performance as president over the next several years? 

 My overriding objective is to ensure our innovative capabilities in medicines and vaccines are connected to the patient. Access to innovation is front and center for me. GSK has had 10 new products approved over the past five years-more than any other big Pharma company-but that success is illusory if patients end up being deprived of therapy. I am committed to mobilizing all our capabilities to face down the whirlwind of pricing pressures and other health system disruptions in order to deliver on this commitment.  

	My second priority is maintaining an internal culture that embraces change in healthcare. The easiest thing to do is to deny, avoid or delay facing up to the challenges of working within a system that requires constant adjustments to accepted practice.  No one likes to make hard decisions that entail risk to your own comfort zone. The GSK culture is built on the motivation we get from the impact our products have on the life of every single patient we serve. Each patient story is unique but in the end it all ties back to the truth that survival in this business depends on being adaptable. 

	The third goal is obvious and immutable-staying close to the marketplace.  What that requires from me and the entire team here is to remain open to experimentation. It is important to me that the US affiliate is able to understand what is happening externally. Our cues have to come from outside. We must know our audiences and what motivates them. What are their pain points? What is changing around their own business and how will this influence the demands they place on us? Only this focus on the customer fuels the appetite for winning.  

Can you point to any “disruptive innovation” that might divert or derail GSK from obtaining these goals? Is this kind of threat from left field baked into your plans?   

 There is a trend I am personally concerned about-the escalation of rhetoric against what our industry does. The intensity of this rhetoric is disturbing and it could lead to decisions with unintended negative consequences, not only for us but for the patient. GSK is committed to sitting 

down with any stakeholder to provide our perspective and help them to shape their own decisions. It also gives us the opportunity to evaluate the level of threat and the prospect of a bad policy choice becoming a business reality. 

	It’s a crucial moment in time, because the adverse political noise coincides with an unprecedented surge in the quality of science coming from our labs. The impact is global:  the WHO says that the world could be polio-free by 2019 due to revolutionary vaccines and other healthcare measures. That’s just one example; HCV is another.  And there is a good chance we will eventually have a cure for the HIV virus. So there is much at stake; to me, the biggest disrupter is regulatory action, taken in the heat of the moment, which could set back progress in medicine and access for patients. This is not an outcome that works for anyone.

’s Editor-in-Chief. He can be reached at 

A conversation with GlaxoSmithKline's US Pharmaceuticals head Jack Bailey.

Steering the Change: GSK's Jack Bailey

As the shift to value-based, personalized healthcare continues, life sciences companies will need to move product conversations away from marketing-centric messages to those that highlight evidence of  efficacy as well as extending the value proposition to include services “beyond the pill.” To thrive in this “facts-beat-marketing-hype” future, companies must embrace a new operating model based on end-to-end (E2E) evidence management across the entire product life cycle. 

	The shift to outcomes- and value-based healthcare, along with more personalized therapies, is increasing the importance of end-to-end (E2E) evidence management capabilities in product development, marketing, and distribution. In the past, a value proposition was driven by  marketing campaigns, claims-based messaging, and scientific sound bites. While clearly based on fact, the value proposition did not highlight the evidence dimension or, if it did, make it central to the measurement of outcomes in the real world. The new market reality is  to require empirical evidence to be positioned at the heart of the value conversation along with patient services “beyond the pill,” rather than on marketing profiles and unit cost and rebate pricing strategies.  

	Given this shift, how should companies manage evidence differently throughout the product life cycle and across the various channels of the healthcare ecosystem? This strategy analysis examines the imperative for E2E evidence management for a “facts-beat-marketing-hype” future. Specifically, this article: 

		Discusses how E2E evidence differs from real-world evidence (RWE), advanced analytics, and big data.

		Outlines essential elements of an E2E strategy, including operating model, partnership, and IT/informatics considerations.

		Frames key components to becoming an insights-driven organization.

		Explores the possible downside implications for companies that have not prioritized the imperative for an E2E evidence strategy.

		Poses questions organizations need to be able to answer under the new evidence paradigm. 

E2E evidence management: Making the case 

	Reimbursement in the healthcare market is shifting toward rewarding value instead of volume; this is also true for pharmaceutical interventions, as seen in an increasing number of outcomes-based contracts in the sector. As a result, life sciences organizations are adapting their product value conversations with payers and other commercial stakeholders to concentrate on evidence around product efficacy, safety, and economic value as well as offering beyond-the-pill services to deliver a more robust value proposition to their customers.  

	Additionally, researchers are targeting more specific disease states based on a growing understanding that patients comprise more than a mass of generic diseases and can be broken down into smaller, defined groups based on

 biomarkers, comorbidities, or treatment pathways. To succeed, these new approaches to drug development require a greater volume and variety of evidence.   

	To mark an effective response to these changes, pharma companies should consider an E2E evidence management strategy (see figure above) as one of the key ingredients to identify targeted breakthrough innovations, rapidly get the new products through development, and successfully launch and market them in a value-based care environment.  

	An E2E strategy will assist organizations in becoming more insights-driven so that decision-makers can act on the basis of rigorous, data-based insights rather than general strategy. Implementing processes to capture and analyze data and to leverage and apply that data for meaningful and sustainable results is a necessity, for a number of reasons: these processes result in better data 

transparency and utilization; provide increased availability of insights to a wider group of people; facilitate less expensive, targeted clinical trials; accelerate product approvals; enable on-target market access strategies; create comprehensive, real-world effectiveness analyses; and help to support new customer engagement models. Ultimately, in the new health ecosystem, evidence is at the core of decision-making, and a strong evidence base will produce more productive conversations with customers and other healthcare stakeholders.

	In Figure 1, we divide the E2E evidence value chain into three components: discovering value, generating value, and optimizing value. During the drug development process, companies should first make portfolio decisions by “discovering value” through clinical trials, then move  to “generating value” through product approvals and compliance and, ultimately, “optimizing value” through commercialization and market access.

	 During early-stage research, evidence management can help an organization discover value by enhancing pre-clinical and clinical research productivity through precise target and patient cohort identification. As concepts mature into products, evidence management may enable an organization to generate value and maximize a product’s potential for clinical and commercial success by leveraging traditional clinical trial data and RWE to segment patient populations for optimal therapeutic response and safety. Finally, when therapeutic interventions are approved and launched, companies can optimize their value by assessing market dynamics to support pricing and market 

access strategies, and by applying RWE to develop, support, and sustain a compelling value story as the products are utilized in a healthcare environment.  

	A strong evidence strategy is cyclical, so the evidence used to optimize product value should also be filtered back to inform new opportunities for therapeutic discovery and development.  Conversely, the pace and disruption of scientific innovation also means that data and insights from the early part of the evidence life cycle should be rapidly leveraged to modify and anticipate shifts in market behavior.  

	E2E evidence strategies and capabilities are no longer a “nice to have;” they are a necessary business component to develop, launch, and sustain successful products. Therefore, the imperative for new E2E evidence strategies and capabilities has implications for technology investments, organizational constructs, and new business models, including external partnerships. 

What are the essential elements of an E2E evidence management strategy?

	Developing and implementing an E2E evidence management strategy requires a level of organizational maturity and insight to move beyond the traditional view of product life cycle management, break down the resulting silos, and incorporate important functions such as strategy, governance, external collaborations, new informatics approaches, and talent management. Evidence management also calls for reducing or eliminating the walls around patient data throughout the R&D process by establishing new platforms that enable end-to-end views of data and analytics centers of excellence to support the new paradigm.  

	Effective evidence management can help to shave off cycle time and dollars from the product development process by informing clinical trial protocol development, thus helping to justify a company’s investment in a certain asset that could impact a new disease area or, conversely, supporting the decision to forego development of a particular product because the evidence indicates low potential for economic success. In addition, an E2E strategy can help increase on-patent revenue generation and keep organizations competitive by being “first to market” and thus contribute to return on investment. 

	The essential components of an E2E strategy can vary by organization-and are likely to involve and impact people, processes, and technology across multiple internal and external touch points. Determining specific needs calls for an assessment of core capabilities such as infrastructure, governance, talent, R&D, and commercialization. 

	A few essential elements are necessary across all organizations for an effective E2E evidence strategy:

		Top-down sponsorship and enterprise-wide alignment.

		Broad understanding of the necessary changes to the organization’s business and operating model.

		A plan for external collaborations to support the new business and operating model.

		Next-generation IT and informatics infrastructure and human capital to support the new model.

How can an E2E evidence management strategy support an insights-driven organization?

	Often, R&D and market strategies are driven by a new technology innovation (e.g., cognitive computing) or a promising data type (e.g., genomics, social media). However, the journey to becoming an insights-driven organization and achieving the promise of E2E evidence management requires alignment and execution across the key components of strategy, people, process, data, and technology (see figure below).

	Some of the questions organizations need to answer about these components include:

 For the patient populations we serve, how will changing science, reimbursement models, and patient behavior impact the need for generating evidence to inform product design, patient care, and overall business decisions?

 Do we have the right talent to make sense of the new types of healthcare information available to us? Who is the accountable business owner for this information? What organizational structure do we need to put in place to support our analytical strategy? Who do we need to engage in other departments and what are their roles? What other talents do we need and what is the plan for acquiring them?  What competencies should we source from external partners?

 How do we ensure that insights are shared across traditional organizational silos? What are the steps we need to take to make these projects a success? How will we comply with relevant regulations? How do we fund and measure the impact of these investments and new operating models?

 What data do we need to answer today’s questions? How do we source data through novel collaborations that our competitors can’t access easily? How do we bring data together and what are the challenges in transforming, linking, and publishing it? How can we improve data quality and accuracy? 

 What technology architecture supports the new needs of expanding sets of data? What tools do we need to process the evidence? What security measures do we need to consider in federated models of data collaboration? How do we scale up the technology when we need to roll out our solution to the rest of the business?

	The process of implementing an E2E evidence management strategy may be complex, and time- and resource-intensive, but the innovation, efficiency, and commercial benefits may help to justify the investment. Moreover, with the right insights, E2E evidence can become a major source of competitive differentiation.

Using evidence across the development life cycle: Five hurdles 

	There are five dimensions of complexity that may make it difficult for life sciences companies to successfully execute an E2E evidence management strategy: disease state complexity, domain or functional complexities, geography, regulations/reimbursement, and operations (see figure below). Each category has implications for a company’s business strategy, operating model, and requisite IT and informatics platforms.

 Understanding and mapping the patient journey for a chronic disease such as diabetes requires different data sources, data sets, informatics approaches, and external collaborations than the patient journey for a rare cancer. As the scientific understanding around a disease evolves, changing definitions, dependencies, or new classifications can result in data and informatics challenges as well as talent and training implications.

 Exacerbating disease state complexity is the fact that an E2E strategy touches every functional domain group in the product life cycle. This means that the design and implementation of every process -from the way partnerships are established, to regulatory compliance, to how third-party data sets are procured-will need to consider the specific needs of the functional groups that will use the data sets.

An “how to” primer for life sciences companies on applying end-to-end evidence strategies in demonstrating product value.

Pharmaceutical Executive-05-01-2016

2016 Brand of the Year: Cancer Standout Opdivo

Steering the Change: GSK's Jack Bailey

Pharma’s Big Push for Value

Pharm Exec at the Vantage Point

Pharma Under Pressure to Curb Opioid Abuse

Country Report: France

Pharmaceutical Executive, May 2016 Issue (PDF)

Pharma Under Fire for Driving "Opioid Abuse Epidemic"