Moving the needle on diabetes

Merck’s Januvia

There are powerful therapies from the pharma industry to combat diabetes, but it continues to be a challenge to public health in the US, and to societies around the world moving up the ladder from developing to developed. Altogether, the disease represents frustrating opportunity both for drug manufacturers and for healthcare systems.

Part of the challenge is that diabetes imposes two major lifestyle burdens on patients: the need to regularly monitor blood glucose levels; and a change in lifestyle in favor of healthy eating and exercise, to take advantage of the proven relationship between these habits and the onset and progression of diabetes. Another part is the lack of symptoms, at least in early stages of adult-onset diabetes, making it harder to change lifestyle and stay on therapy.

The opportunity: the biopharma industry has developed a wide array of powerful treatments, and there is intense competition among manufacturers to put their products forward as the best option. And with a large and rapidly growing market, there are resources to both market products aggressively and to complement those products with a variety of patient-support services.

Sanofi’s Lantus Solostar injectable pen

Prevalence and cost

According to World Health Organization data, 347 million people worldwide have diabetes, up from 153 million in 1980, and by 2030 that number is expected to reach 472 million. Today, “more than a third of all Americans have diabetes or prediabetes—a trend that has been going on for more than two decades,” said Sam Dagogo-Jack, MD, president, medicine and science for the American Diabetes Assn. (Alexandria, VA), in a March 2015 statement.

Today, all stakeholders are agitating to come up with game-changing solutions—some are pursuing ongoing advances in insulins and other anti-diabetic medications, needle-free alternatives to drug delivery, and improved glucose-monitoring techniques. Others are developing customized patient-support networks that aim to remove some of the recognized clinical and financial issues that often impede reliable drug adherence over time. Still others are developing novel programs and modalities to promote desired behavior modification, in order to address the psycho-social and logistical impediments, and help patients break through the fog of denial and apathy in order to increase the duration of crisis-free diabetes management. All approaches are aimed at reining in the runaway costs to patients and society.

Spending on medications for diabetes in the US increased by 30.5% over 2013 levels—reaching $32.2 billion/year, according to IMS Health data (Fig. 1). Thanks to some aggregate manufacturer discounts and rebates in this disease category, net spending growth in diabetes was 22.4%—but that’s still nearly twice the rate of overall pharma spending growth.

On a global basis, spending on diabetes treatments is expected to exceed $78 billion globally in 2018, according to the IMS Institute. “A variety of demographic and epidemiological factors are driving diabetes incidence rates, demand for medications and overall costs. Some have been good for the pharma industry (increasing demand for medications) but many also create a variety of challenges,” says Michael Kleinrock, research director at the IMS Institute for Healthcare Informatics (Parsippany, NJ).

Last year proved to be a pivotal one for diabetes in the US, thanks to the nearly 16 million Americans who gained health insurance coverage through the implementation of the Affordable Care Act (ACA) and the expansion of Medicaid and Health Insurance Exchanges (HIXs). According to 2013 data from the American Diabetes Assn., people with diabetes who lack health insurance have 79% fewer physician office visits and are prescribed 68% fewer medications compared to people with insurance coverage. However, they also have 55% more emergency department visits than people with health insurance.

In the first full year of enrollment for expanded Medicaid and health exchanges under the ACA, patients with Medicaid in states that had expanded eligibility filled prescriptions at a rate that was 25.4% higher than in the prior year, compared to growth of just 2.8% in non-expansion states, IMS found.

Afrezza, recently approved by FDA, will address patients’ resistance to self-injection. Credit: Sanofi

Patient by patient

Drug cost and the availability of insurance affects usage patterns significantly. The Health Care Cost Institute (HCCI; Washington, DC), found that, for the years 2009—2013, per capita healthcare-related spending for individuals diagnosed with diabetes was $14,999/year—more than three times higher than the healthcare spending for individuals without diabetes ($4,305/year). People with diabetes had average per capita out-of-pocket (OOP) healthcare expenses of $1,922/year—2.5 times more than the average OOP spending for people without diabetes. OOP expenses include insurance copay or deductible for medications, doctor visits, medical supplies and OOP expenses associated with any additional hospitalization or emergency room visits, says HCCI senior researcher Amanda Frost, PhD.

Interestingly, HCCI’s study showed that among the individuals with diabetes, the two sub-groups that had the highest per capita healthcare spending were children (ages birth through 18 years; $15,456/year in 2013), and pre-Medicare adults (ages 55 through 64 years; $16,889/year in 2013).

Preference for branded insulins helped to drive these higher levels of spending, especially among younger patients. “Among children, we see especially high spending on branded insulin,” says Frost. In 2013, an average of $2,511 was spent on branded insulin per child with diabetes—more than four times what was spent on branded insulin for middle-aged adults ($589) and pre-Medicare adults ($617). Part of the explanation for this, says Frost, may be that “there have been advances among insulin in recent years and this may be one influence on the use of branded products.” Another factor that may be driving this preference and demand for branded insulins among children is that parents typically want what is perceived to be the best for their children, and are potentially more rigorous about maintaining adherence.

“This work provides a starting point for further analysis and research, to help understand the drivers behind these spending trends,” says Frost. “And of course, the next step in the research is to really think about the connection between these healthcare dollars and patient outcomes.”

Insulin advances

Today, the lion’s share of total drug spending in diabetes—63%—still goes for insulins—and insulins accounted for 61.3% of spending growth in 2014, according to IMS Institute. For this reason, many industry analysts are eagerly anticipating the eventual arrival of biosimilar insulins in the US, feeling that they will have a big impact on the drug-spend patterns.

Glargine, best known as Sanofi’s Lantus brand, is both the highest dollar-volume insulin therapy, and the earliest opportunity for biosimilar commercialization. The first biosimilar glargine in the US received tentative FDA approval in August 2014 via the 505(b)(2) pathway, and could launch by 2016, pending resolution of patent litigation with Sanofi. The biosimilar insulin glargine from Lilly and Boehringer Ingelheim is already approved in the EU since late 2014 for use in type 1 and type 2 diabetes patients, age 2 and up. Several other companies are also developing biosimilar versions of glargine, including Merck and Mylan.

“There’s still a lot of reasons to think that doctors will be skeptical about biosimilar insulins—given some skepticism about substitution and interchangeability, reimbursement (who pays and what are the financial incentives), and ambiguous outcomes,” says Kleinrock of IMS Institute. “But once there are approved biosimilar insulins on the market, even if they are not interchangeable, it would seem to be almost a no-brainer for payers and doctors to consider their use.”

“As a result, we expect that when the floodgates on biosimilars finally open, we will see a short, sharp shock of big adoption,” Kleinrock continues. “Even though insulins are already relatively inexpensive, getting them cheaper will still be very valuable for the patient, providers and payers.”

Meanwhile, oral forms of insulin have been pursued for many years but thus far none has come to fruition. Nonetheless, the idea of substituting daily pills for daily injections has obvious appeal, and could help drive adherence in a meaningful way. Given the appeal of an insulin in tablet form, many companies, including Novo Nordisk, Eli Lilly, Pfizer, Sanofi-Aventis, Oramed and Biocon, are working on this.

Non-insulin treatment options

Beyond insulins, several newer categories of non-insulin diabetes therapies, which aim to help the pancreas to produce more insulin or the body to use it more effectively, continue to generate interest. Among the leading categories of non-insulin antidiabetics are:

• DPP-4 inhibitors (glitipins), which work by blocking the action of DPP-4, an enzyme that destroys the incretin, an important hormone that regulates glucose use and production in the body. The market leader is Merck’s Januvia, a tablet. A study released at the June ADA annual meeting demonstrated Januvia’s lack of harm to the heart—a side effect that implicates two other DPP-4s, AstraZeneca’s Onglyza and Takeda’s Nesina.
• Oral glucogen-like peptides-1 or GLP-1s (which are incretin hormones that stimulate the secretion of insulin from the pancreas). Novo Nordisk’s Victoza has been on the market for several years, as has Lilly’s Trulicity. Sanofi is expecting to seek approval for Lyxumia, already marketed outside the US, following completion of a trial this spring.
• Sodium-glucose transporter-2 inhibitors or SGLT-2s (gliflozins), which lower the renal glucose threshold, resulting in more glucose being excreted in the urine. Top brands are J&J’s Invokana, AstraZeneca’s Farxiga and Lilly’s and Boehringer-Ingelheim’s Jardiance. In May, an FDA warning was issued about a possible side effect of SGLT-2s, known as ketoacidosis.

Collectively, these three categories now account for 31.4% of diabetes drug spending in the US, according to IMS Institute. By comparison, spending on some of the older non-insulin diabetes therapies, including sulphonylureas (which help the pancreas to produce more insulin), biguanides (which help the liver to produce less glucose), and glitazones (which help to lower blood glucose), decreased by 16.3% in 2014, declining to a current level of $1.7 billion/year.

“Oral forms of GLP-1s and oral forms of insulin (as an alternative to subcutaneous injections) that are currently being pursued are considered by many to be the Holy Grail in drug-development efforts related to type 2 diabetes,” says Todd Hobbs, MD, chief medical officer, North America, for Novo Nordisk. He also notes that in type 1 diabetes, “The bionic pancreas and islet cell/beta cell encapsulation are also being pursued as radical innovations.”

Pursuing a different approach to help diabetics reduce the logistical and emotional burden of the complex daily medication regimen (often involving numerous pills and injections every day), Boston-based Intarcia Therapeutics has developed an investigational treatment that moves its drug dosing from a daily to a once-yearly frequency. Now in late-stage clinical development, ITCA 650 allows for long-term, steady-state dosing of exenatide (an incretin mimetic therapy) to help patients achieve glycemic control and encourage weight loss. The company’s implantable, miniature osmotic pump is placed beneath the skin to provide continuous delivery of exenatide, a GLP-1 receptor agonist, currently marketed globally as a twice-daily and once-weekly self-injection therapy for type 2 diabetes. The company hopes to file for regulatory approval in early 2016.

To date, there is only one inhalable insulin product available in the US. Last February, Sanofi launched its inhalable insulin product in the US. The product Afrezza, was developed by Mannkind. The product uses a small, whistle-sized inhaler, to provide a fast-acting form of insulin to help control blood glucose in both type 1 and type 2 diabetes. Afrezza’s smaller device design is expected to be more practical and appealing for patients (helping to address one of the reasons behind the market failure of Pfizer’s Exubera form of inhalable insulin, which was approved by FDA in 2006, but failed in the marketplace).

Differentiation by efficacy only gets a manufacturer so far in today’s market. “The pharma industry as a whole, and specifically the diabetes sector, is seeing a trend with payers attempting to commoditize therapeutics and downplay incremental innovation,” says Hobbs of Novo Nordisk. “Payers then will typically use this fact to assert that there are no immediate clinical advantages of a newer product over another, and thus move to price/rebating as the main means of determining formulary status.”

“The potential impact of ongoing innovation in drug-delivery systems and devices related to diabetes should not be ignored, as these innovations may help to remove barriers to adherence and help a select set of patients better manage their chronic disease,” says Amy Grogg, PharmD, SVP of strategy and commercialization for AmerisourceBergen Specialty Group.

Changing behaviors to drive adherence

“Because type 2 diabetes is so directly influenced by patient behavior, there is no single “magic bullet” therapeutic option that will advance diabetes care to where it should be in the United States,” says Hobbs of Novo Nordisk. “We believe that significant public health initiatives and programs to focus on increasing overall healthy lifestyle choices are essential.”

“In diabetes, it’s not just about inventing new and better drugs,” says Kleinrock of IMS Institute. “We’re all finding that the challenge is to also develop support programs and tools that keep the messaging and outreach fresh and engaging, so they can help patients to overcome the emotional obstacles and battle fatigue that is so emblematic of this vexing illness.”

Diagnosed diabetes imposes an overall cost of around $250 billion in the US, according to a March 2013 study released by the American Diabetes Assn. Costs include $176 billion in direct medical expenses and $69 billion in reduced productivity (through absenteeism, lost productivity among the employed, and lost productivity capacity due to early mortality).

“In fact, retail prescription diabetes medicines have consistently accounted for just about 12% of healthcare spending for diabetes in the US,” adds Hobbs of Novo Nordisk. “This underscores why helping patients to stay healthy and manage chronic disease, and to use innovative medicines appropriately, can help to defray unnecessary utilization of costly ER visits, hospitalizations, and expensive medical procedures and thus bring down the overall cost of diabetes care.”

“Treating diabetes often involves complicated regimens, even when insulin is not part of the picture,” says Kelly Blinzler, VP, global market access for Kantar Health (New York, NY). “And patients are on multiple therapies, so the more products they take, the more challenging it is to remain adherent.”

Patient support

Today, nearly all diabetes brand teams and many payers offer disease- and drug-management programs to support their patients. At a minimum, these opt-in programs offer reminders for physician appointments and prescription refills. Drug companies work with third-party partners to establish hub-type programs to centralize and streamline access to the various types of clinical and financial support tools that are needed by patients, caregivers and physicians. “Depending on how they are structured and carried out, these programs have varying levels of success, partly because they are generally voluntary, and partly because many diabetes patients may or may not believe the seriousness of their disease, especially when it is asymptomatic,” says Blinzler of Kantar Health.

“The goal of any hub services plan is to provide a single point of contact for accessing complex information about insurance coverage, any applicable copays, opportunities for financial assistance (through coupon and copay-offset programs, free trial offers, patient assistance programs and more), and educational programs and resources to support healthy lifestyle choices and manage drug therapies,” says Jillian Gilbert, executive account manager for Triplefin, a support-services provider that is part of the wholesaler H. D. Smith. Interestingly, while the hub model has been traditionally reserved for costly specialty drugs that have significant disease- and drug-specific informational needs associated with them, diabetes is one disease category that has been shown to benefit from a modified version of a classic hub services program.

“While the unit cost of most diabetes drugs is relatively low (compared to traditional specialty drugs that traditionally warrant full hub service treatment), the downstream cost of diabetes-related health problems and co-morbidities is so great—thus the types of value-added, wraparound services are often justified, to help patients manage their diabetes and avoid the costly, downward spiral that results from failing treatment efforts,” adds Kleinrock of IMS Institute.

Care-management programs that have proven to be successful in dealing with issues such as medication, nutrition, lifestyle, affordability and more in the specialty space can absolutely inform how brand teams develop programs to help patients manage disease states like diabetes and hypertension, asserts Grogg of AmerisourceBergen Specialty Group, whose Lash Group subsidiary is a major hub-services provider.

“Some pharmaceutical companies are partnering with service providers who have developed ways to segment patients based on their risk of noncompliance, and then provide more-targeted services based on where the patient is along the adherence risk spectrum,” says Grogg. She adds that, increasingly, these patients are expected to interact with support services using technology such as smartphones for added convenience.

“When drug manufacturers can develop a flexible framework, they can right-size the service offerings for patients, offering a mix of high-tech and high-touch solutions to address access, affordability and adherence,” adds Grogg.

“A successful, modified hub program combines intensive training and an approach to follow-up that fits the motivators of the patients,” says Blinzler of Kantar Health. She notes that when programs are modeled after successful weight-loss programs such as Weight Watchers—which require a level of motivation, but also provide interaction and ongoing measurement—they tend to be successful. It’s human nature to want to ‘pass,’ ‘do well’, and part of that success is being sure that others know you are succeeding, and knowing how you are doing compared to others.”

Most manufacturers of diabetes therapies offer opt-in support programs: Novo Nordisk is managing a patient-support program branded as Cornerstones4Care, with an emphasis on educational materials in the patient journey. The program offers a free, personalized action plan with resources that patients can access 24/7 to help them manage their diabetes. “Patients can set their own preferences to view content—related to healthy eating, remaining active, managing medications and tracking blood glucose levels, and understanding patterns tailored to where they are in their diabetes journey to help access the right support at the right time,” says Hobbs.

AstraZeneca launched Fit2Me.com for Type 2 diabetes patients last year; Merck has MerckEngage, a health and wellness resource for multiple medical conditions; Lilly supports a variety of ADA-managed programs.

The newest type of patient support is gamefication: using online games and reward programs to encourage the right habits and to maintain therapy. HealthPrize Technologies (Norwalk, CT) markets its services to pharma companies, and has been engaged in a number of efforts with unspecified drug manufacturers addressing diabetes. A January report from the company notes that Type 2 diabetes patients spent an average of 43 minutes per month on the site and overall, the mean interval between refills dropped by 39% (implying greater adherence).

A similar service, called RedBrick Journeys and marketed to employer health plans, comes from RedBrick Health (Minneapolis, MN). “To a large degree, wellness program designs continue to use legacy approaches to health improvement, and traditional one-size-fits-all or lightly tailored online educational programs that fail to inspire frequent interaction, thus they often have limited impact on shaping habits and producing improvement in objective health measures,” says Eric Zimmerman, MPH, MBA, chief marketing officer for Redbrick Health. RedBrick’s Journey program breaks an overall program down into incremental steps that patients can follow; a two-year study of 182,000 patients in the program showed significant reductions in risk factors for weight, blood pressure and other health measures that are often related to chronic diseases.

“Many mobile apps are being developed by healthcare providers, but the early versions have been mostly focused on keeping the appointment or looking at the bill,” says Kleinrock of IMS Institute. Today, there is ongoing effort to develop apps and online platforms that are focused on the behavior modification, for instance, first remind someone, then offer some reward, then keep score of adherence to medications and allow a physician to intervene when there is a pattern, he adds. “The important thing is to design the program in such a way that allows the physician to intervene at the right time. If the doctor called after you missed your first pill, that could be creepy and invasive, but if the app captures a longer pattern of non-adherence, it may become more acceptable for the doctor to reach out.”

Some pharmaceutical companies are developing high-tech and interactive software tools designed to import and analyze retrospective medical and pharmacy claims data to help pharmacy directors, medical directors, and other decision makers understand current patterns of care in the management of diabetes and identify opportunities for potential quality improvement initiatives including those focused on adherence, notes Grogg of AmerisourceBergen.

Manufacturers are also trying to address diabetes from a population health perspective. Novo Nordisk recently helped launch the Cities Changing Diabetes initiative, which is engaged with Denmark’s not-for-profit Steno Diabetes Centre and University College London (UCL; London). “Our goal is to better understand the driving factors behind the rise of diabetes in urban areas, and to share that knowledge, with an emphasis on the behavioral and cultural drivers in urban diabetes, and then develop and apply tailored, real-world solutions,” says Novo Nordisk’s Hobbs. To date, Copenhagen, Mexico City, Shanghai, Tianjin and Houston have joined the initiative.

Last March, Accenture Life Science’s most recent High Performance Business (HPB) study named Novo Nordisk as the top performer among a group of 18 multinational pharma companies, lauding the company’s efforts related to science-based growth, patient outcomes and commercial success, citing, in part, the Cities Changing Diabetes program.