THE ONGOING DIABETES BATTLEGROUND

Although diabetes has been high on the radar screen of healthcare providers and public health administrators for years, the number of patients (mostly Type 2, or adult-onset) continues to rise—and at a pace that is accelerating. The Centers for Disease Control and Prevention counted 18.8 million diagnosed cases in 2010, and 7.0 million undiagnosed—25.8 billion total, or 8.3% of the US population. Longitudinal data show that cases and have risen from 10.87 million in 1999 (4.0% of population) to 20.67 million (6.86%) in 2009. The frustration arises because not only is the disease preventable for a large proportion of patients (by changes in lifestyle and diet), even patients already under treatment seem to be flipping a coin whether to actively manage their disease and prevent its progession—or not.

Diabetes treatment was the fastest-growing segment, in dollar value, among 14 therapy classes tracked by IMS Health, with overall sales of $16.9 billion in 2010, up 12.5% from the year before. Pharma manufacturers, besides developing an impressive list of new treatments, have been investing in a range of ancillary services for patients and providers to try to bring some control onto the disease, including medication adherence, health coaching and social media—all with mixed success.

Everyone hopes for a formula to bring the condition under control because the outlook continues to worsen. Some 79 million Americans have prediabetes (meaning that they have multiple risk factors that could lead to full-blown diabetes). And at a global level, diabetes is growing, especially under newly industrialized nations. Worldwide, the World Health Organisation (Geneva) estimates that 346 million people have diabetes. WHO has brought several global health organizations together under an umbrella of “non-communicable diseases” (including cancer, heart disease, chronic lung diseases and stroke), which is the subject of a high-level global forum as the United Nations convenes this September; the theme is “Unite in the Fight.” (Fig. 1)

Pipeline progress

“In recent years, a real urgency to innovate has driven the pursuit of several new classes of medicines in diabetes therapy, each with a distinctly different mechanism of action,” says Brian Lasky, senior principal with IMS Consulting Group (Collegeville, PA). The introduction of non-insulin antidiabetic medications in two novel classes — the GLP-1 agonists and the DPP-IV inhibitors — “provided breakthroughs that were completely different than what we had in diabetes care before.”

The glucagons-like peptide-1 (GLP-1) agonists include Byetta and Bydureon

(not yet approved in the U.S.) from Eli Lilly/Amylin Pharmaceuticals, Victoza from Novo Nordisk, and others. The dipeptidyl peptidase-IV (DPP-IV) inhibitors include Januvia from Merck, Galvus from Novartis AG, Tradjenta from Eli Lilly, Onglyza

from Bristol-MyersSquibb/AstraZeneca, and others.

Today, many are eagerly awaiting the FDA approval of the several new medications in the latest class of antidiabetic therapies — the SGLT-2 class (SGLT stands for sodium glucose transport inhibitors). While the mechanisms of action (MOA) of existing anti-diabetic medications help the body to either increase insulin secretion or reduce insulin resistance, Lasky notes that “the SGLT-2 class of diabetes therapies is truly innovative, as these medications will be the first of their kind whose MOA is to remove excess glucose — the offending item — from the body, by increasing the amount of glucose eliminated by the kidneys.” Investigational data show that this can lower blood glucose levels and help to reduce body weight.

The SGLT class has the potential to complement every other course of diabetes therapy, says Lasky, thus enhancing those therapies. Today, dapagliflozin from AstraZeneca/Bristol-Myers Squibb is expected to be the first to launch (as it has been filed with FDA); however, an FDA Advisory panel recently voted against approval of dapaglifozin due to possible cancer risks. Johnson & Johnson’s canagliflozin and Boehringer Ingelheim’s empagliflozin are in Phase III, and several other companies have SGLT-2 compounds in Phase II development.

Moving the needle in diabetes care

The lack of an out-and-out cure for diabetes, combined with the complexity of treatment regimens, and the resistance of patients to do what’s best for themselves, adds up to a challenging environment for marketers and health service providers. “I can think of no other chronic disease where the burden for success lays more heavily on the patient versus the physician — if a person is not willing to dramatically and permanently alter his or her lifestyle and eating habits, no medicine, therapy or physician can save them,” says Paul Harrington, SVP and creative director at Palio (an inVentiv Health company), who has pharma clients that are primarily focused on the Type 2 diabetes market. “This creates a heavy responsibility for the patient, and the resulting tension between patients and healthcare providers creates a minefield of frustration for all parties.”

“Now more than ever, with healthcare quality and outcomes tied to aspects of practice management, it is not surprising that physicians feel frustration when they cannot convince patients to change their lifestyle habits,” says Mary Easterday, VP, account group supervisor of Torre Lazur Managed Markets (Parsippany, NJ).

“Poor patient adherence is the primary barrier to successfully managing diabetes, and we are repeatedly reminded through research that for many patients with diabetes, there is a fundamental disconnect between appropriate self-care and the improvement in their condition, and self-esteem issues often complicate this problem,” notes Carolyn Gorelick, VP and account group supervisor for Regan Campbell Ward Group, a McCann Healthcare Worldwide agency. The financial burden of testing supplies and medications creates another barrier to adherence.

But these challenges “also present great opportunities for brands that understand and appreciate that the complexity of the physician-patient relationship and the role of well-defined and useful communications that support physicians can be a critical success factor for any brand,” says Harrington.

Pharma marketers have evolved a multi-pronged approach to diabetes: traditional sales calls, advertising and education materials for physicians; support for patients (either directly, when patients opt in, or indirectly through healthcare providers); and support services and care coordination with retail pharmacists. In the latter case, manufacturers are working with the major wholesaler-distributors, who bring both their distribution capabilities to the table as well as their relationships with chain drugstores and independent pharmacies. Standing behind all of these interactions are payers, who are constantly evaluating the combination of drug efficacy and outcomes against cost, and making decisions based on how well the drugs perform when the entire spectrum of drug, delivery channel and patient support are combined.

“We know that the average person living with diabetes spends only six hours with their doctor in a given year, which means they are left with 8,754 hours to manage the condition on their own,” points out Dennis Urbaniak, VP, US Diabetes, for Sanofi US (Bridgewater, NJ). He also cites American Diabetes Assn. numbers that show that at least 60% of patients do not follow their diabetes treatment regimen as prescribed. “And roughly 40% of people living with diabetes are not in control of their blood-sugar levels, leaving them at an increased risk of developing diabetes-related complications.”

“No two cases of diabetes are identical, so when we work with patients who opt in to receive educational materials (for instance, through our Cornerstones for Care program), we rely on their answers to specific survey questions to guide us on what type of specialized outreach is most appropriate for that patient at that time,” says Pat Quinn, Director of Trade for NovoNordisk (Princeton, NJ). “It’s basic behavioral change that is needed. That’s why it’s such a challenge. With greater knowledge of where that patient is on his or her diabetes journey, we are able to slot that individual into the right branch of the information tree and then tailor the outreach efforts much more meaningfully.”

Working with the Big Three distributors—McKesson, Cardinal Health and AmerisourceBergen — drug and device manufacturers are developing creative disease-management initiatives and other health-promotion programs that are aimed all participants in the diabetic’s care and support team. “With the escalating number of people with diabetes, and the increased demands these patients put on the healthcare system, the opportunity for pharmacists to provide patient support is essential,” says Ceci Zeigler, LPN, National Director, Patient Care Services for AmersourceBergen (Chesterbrook, PA). “The ability of pharmacists to have these face-to-face interventions positions them as an integral, visible part of the support team.”

“Behavioral coaching sessions, sponsored by manufacturers, offer the opportunity to address patient-specific adherence barriers in a comfortable and trusted conversation with pharmacists who are trained in motivational interviewing techniques and health-behavior change,” says Peggy Yelinek, VP and GM, McKesson Patient Relationship Solutions (Scottsdale, AZ). To date, more than 9,100 diabetic patients have received a behavioral-coaching session through McKesson’s Pharmacy Intervention Program. Similarly, with support from Novo Nordisk and Bayer Diabetes Care, McKesson sponsors the Health Mart Healthy Living Tour, which features a mobile screening unit that travels across the U.S. to raise diabetes awareness and provide free health screenings, enables pharmacists to increase their visibility within the community. “Nearly 50% of the people screened during the inaugural 2010 Tour were identifies as being at risk for diabetes,” notes Yelinek.

Meanwhile, Cardinal Health serves roughly 7,000 independent pharmacists and more than a dozen chain pharmacies, and provides the tools and training (including discounted access to continuing education courses and a patient-focused curriculum on different diabetes topics, so pharmacists can host group education classes and individual counseling sessions with patients. The goal is to help pharmacists to work more closely with their patients to improve diabetes-related outcomes. “Many of our pharmacy customers are looking for ways to diversify their revenue as a means to offset shrinking margins,” says Kirsten Hochradel, manager of Cardinal Health’s Diabetes Specialized Care Centers. “At the same time, many retail pharmacists also want to offer healthcare services (such as expanded diabetes care) because doing so really fulfills their desire to play a meaningful role in improving patient health.”

Similarly, AmerisourceBergen offers the 3,700+ community pharmacies in its Good Neighbor Pharmacy program (about half of which have pharmacists who have taken extra training to become part of the company’s Diabetes Shoppe program) a range of ADA-approved educational support materials and training “so they can become their community’s “diabetes destination point,” says Zeigler.

Meanwhile, with funding from NovoNordisk, Good Neighbor Pharmacy (along with Innovative HealthCareDesign) created a double-sided, table-top flip chart called “10-Minute Consult,” which is available to members of the Diabetes Shoppe program. The clinician side of the chart, which is not visible to the patient, includes conversation prompts (based on motivational interviewing principles) and key clinical messages (more than 30 modules range from insulin delivery to portion control). The patient side of the chart features bullet points to reinforce the clinician’s message. The program also supplies patient handouts.

Sometimes, the pharmacy channel is used to support a particular medication. For instance, to support patients who have been prescribed Victoza (a once/daily injectible drug that spurs insulin production in the pancreas in response to changing glucose threshold levels), NovoNordisk has assisted in training 29,000 pharmacists across 7,000 Walgreens outlets. At the patient’s first fill of a Victoza prescription, the pharmacist pulls the patient aside to discuss how the drug works and is taken, and its possible side effects. “Pharmacists can provide a lot of value by taking advantage of that ‘teachable moment’ — the first prescription fill — with the patient, and the patient benefits by getting questions answered beyond the package insert,” says Quinn.

Meanwhile, the ability for pharmacist support is not limited to face-to-face settings. For instance, through its Therapeutic Resource Centers, Medco continues to expand the reach and capabilities of its mail-order pharmacists by training pharmacists in particular chronic conditions, to help them develop deeper levels of expertise and counsel and support patients more effectively. “The ability to help patients with diabetes manage their disease better not only benefits patients, but because it can help to rein in healthcare costs, such efforts benefit employers and health plans, as well,” says Joan Kennedy, SVP at Medco Personal Health Solutions, the Franklin Lakes, NJ, PBM.

In addition, Medco’s recently launched Diabetes Center for Healthy Living (MDCHL; part of a Medco subsidiary, Liberty Medical) is providing clinical and moral support to people living with diabetes and co-morbid conditions such as hypertension, elevated cholesterol, foot problems, eye problems and so on. Along with diabetes pharmacists, the MDCHL clinical staff include Certified Diabetes Educators, nurses, dieticians, insulin pump trainers, respiratory therapists and other specialists. “Through live, telephonic and online communications, and a large library of educational materials, Liberty provides patients with personalized education and support, and runs an insulin pump center that provides healthcare providers with 24/7 access to pump specialists,” she adds.

The drug-delivery component

How diabetes drugs are delivered is yet another dimension to their commercial success, say marketing experts, and the range of options include oral solids, injections, and insulin pumps (primarily for Type 1). Today, the majority of marketed non-insulin antidiabetics are oral drugs taken in tablet form, and the pipeline continues this trend, with 63% of developmental agents using an oral delivery mechanism, according to a March 2011 report by market research company Datamonitor (New York). Several antidiabetics (such as the GLP-1 agonists), rely on subcutaneous injection, “which may be an obstacle in comparison to oral therapies, although advantages in efficacy or weight loss have enabled the GLP-1 agonists to gain market share,” according to the report.

Despite the fact that insulin use is usually reserved for third-line or later therapy for patients with Type 2 diabetes, “insulin use is on the rise, which is not surprising as it is becoming increasingly difficult for patients to sustain long-term control, and physicians are prescribing insulin more often in combination with other therapies,” says Gorelick of Regan Campbell Ward.

Similarly, “while the death of the syringe is still a long way off, there are certainly signs that more and more patients will be putting down the needle and picking up a new tool to deliver their lifesaving diabetes therapy,” says Harrington of Palio. These include a push for tubeless, less invasive/intrusive insulin pumps for patients with Type 1 diabetes. And to ease self-administration and boost adherence for patients in the Type 2 category, drug makers continue to pursue commercialize non-syringe/non-oral mechanisms for delivering insulin. However, to date, problems and setbacks continue to plague the developmental efforts related to inhaled insulin (using nasal or inhalation pathways) and transdermal patches. Thus, industry observers say that any game-changing breakthrough in that arena is still likely to be years away.

The most promising advances continue to be related to improving the needle technology, with the industry seeing “really impressive improvements,” in recent years, says Lasky. For instance, ongoing advances continue to focus on efforts to develop smaller, thinner needles, improved spring-loaded pen devices (which require less plunger pressure to deploy the device), and several companies are working “to integrate or link several technologies that will enable both patients and healthcare professionals to make better realtime treatment decisions,” adds Quinn of NovoNordisk. These include, for instance, efforts to devise pen delivery devices that could also serve as a glucose meter and be linked to the patient’s smart phone to collect and manage the data.

Patient outreach

Despite the promise of these technological innovations, the main obstacle today remains connecting with the patient’s self-interest in caring for themselves. The rapid changes coming from social media are being looked on with some optimism, although the regulatory framework for communicating with patients is still undefined (Pharmaceutical Commerce, July/Aug, p. 1).

“Dialogue between patients in these online settings also provides the company with useful insights into the condition,” says Urbaniak of Sanofi US, which now has a presence on Facebook, Twitter, Youtube and a blog (discussdiabetes.com). Abbott, Pfizer, Johnson & Johnson, Eli Lilly GlaxoSmithKline and AstraZeneca are among others that also maintain diabetes-related blogs.

While critics charge that the social media milieu is built on sound bites that enable — at best — only superficial exchanges of information, this aspect may actually be helpful when it comes to disseminating information related to diabetes and other chronic conditions. “Diabetes education can be overwhelming, especially to the newly diagnosed, but a daily nugget of helpful information is easy to handle and can be immediately used,” says Kennedy of Medco.

Meanwhile, one industry observer notes that “Today’s many forms of social media provide both the best and the worst in terms of messaging opportunities,” because the unbridled nature of the media makes it hard to track adverse events and virtually impossible to curb the viral dissemination of wrong or misleading information put forth by even the most well-intentioned yet misinformed writers, who may remain anonymous online.

While drug companies routinely use online channels (such as branded and unbranded websites) to share information with patients and create opportunities (through opt-in controls) to foster a two-way dialogue and customize specific educational materials to be sent to patients, caregivers and healthcare providers, many drug companies are treading very lightly into the murky waters of social media. “It’s natural for all drug companies to say ‘We don’t want to open ourselves up to sit where we can’t have some control over the content of the messaging,’” says Quinn of NovoNordisk.

Partly at issue are HIPAA requirements and the pharma industry’s regulatory obligations related to adverse event reporting also muddy the waters. “With so many people saying so many things about their experiences with different diseases and medications, are drug companies supposed to respond to someone who casually mentions an adverse event they experience in some online forum? Are we obliged to follow up with the person, or report it to the right authorities?” says the industry observer. “Things can get very dicey.”

Garnering payor support

“One of the biggest trends we are seeing right now in the US is that, due to a general lack of sufficient outcomes data and ongoing formulary pressure from payors, physicians tend to use the safest or the cheapest drugs available but these may not necessarily be the best drugs for the patient with diabetes,” says Lasky of IMS. “This is penny-wise and pound-foolish because uncontrolled diabetes can engender increased hospitalizations and other medical interventions, which are more costly in the long run.”

“Diabetes is high on the radar of health plans,” says Easterday of Torre Lazur. “However, newer payer dynamics seem to be emerging, with some payors beginning to play a more active role in limiting access to certain drugs in the diabetes category.”

For instance, according to Easterday, late last year, a major health plan made a decision to move a rapid-acting insulin from Tier 1 to Tier 3—a decision that increased the out-of-pocket cost to some patients by 250%. “Pharma manufacturers must develop and deliver compelling product and service value propositions to shift the debate with payer from ‘the cost of the medications’ to ‘the value they provide’ [in terms of reduced long-term healthcare costs] if they are to ensure that patients can continue to access medications at a reasonable cost,” she says.

“We work closely with payors and PBMs to demonstrate the value of their medications,” adds Quinn of NovoNordisk. “If the right health economics and clinical outcomes data can be developed to show that a given medication can reduce emergency room visits or hospitalizations, pharma companies will be able to demonstrate the product value—not just for the patient, but for the payor who is ultimately footing the bill.”

Toward that end, drug companies should pursue opportunities in two parallel tracks, says Easterday:

* They should work closely with payors to provide non-branded, value-added partnership programs (such as disease-management tools, patient education, drug-compliance initiatives) to plan members, to improve the health outcomes for members beyond what the drug spend alone can achieve

* To seek the most advantageous formulary placement and coverage decisions, drug companies should work to develop the most compelling messaging (in terms of clarifying the full value proposition with clinical and economic data) to present to key decisionmakers at each health plans and PBMs.

“These are exciting—if somewhat heated—times in the diabetes market,” says Harrington of Palio. “But it’s getting crowded, and a la Darwin, only the strongest will survive.” PC