Erin Johanek, PharmD, RPh

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Hyperlipidemia is an increased amount of lipids, such as cholesterol and triglycerides, in the blood. Hypercholesterolemia, a high level of low-density lipoprotein cholesterol (LDL-C) in the blood, increases fatty deposits in arteries and, in turn, the risk of blockages, according to the 

“Cholesterol is one of the primary causal factors in the development of atherosclerotic cardiovascular disease which leads to strokes and heart attacks,” says Luke Laffin, MD, a cardiologist at Cleveland Clinic. “Hyperlipidemia screening occurs in about 70% of U.S. adults and, based on more contemporary American cholesterol guidelines, it has been estimated that, between 2016 and 2025, 12.24 million more Americans will be treated with statins, increasing treatment costs by $3.9 billion.”

Laffin also says that, with the increasing availability of therapies for hyperlipidemia to decrease patients’ cardiovascular risk, managed care systems will have to balance the increased costs and multiple choices for cholesterol and triglyceride reducing medications. He adds that absolute cardiovascular risk reduction in an asymptomatic population may only derive benefits 15 to 20 years down the road.

One of the most recently-approved classes of medications for the treatment of high LDL-C is the proprotein convertase subtilsin-kexin type 9 (PCSK9) inhibitors. PCSK9 inhibition increases the number of available LDL receptors on hepatocytes to clear LDL-C, resulting in decreased plasma LDL-C. There are currently two PCSK9 Inhibitors approved by the FDA: Sanofi/Regeneron’s Praluent (alirocumab) and Repatha (avolocumab) from Amgen.

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“The high cost of the PCSK9 Inhibitors presents a huge barrier for patient access, as a number of health insurance companies do not want to cover them,” says Megan Harrington, PharmD, clinical staff pharmacist, Gerald Champion Regional Medical Center in Alamogordo, New Mexico. “Measuring these drugs against treatments like statins will prove to be difficult because these traditional methods are tried and true with years of safety and efficacy data at a very affordable price tag.”

Vascepa (icosapent ethyl) from Amarin Corp. recently showed significant cardiovascular risk reduction by lowering serum triglycerides in the REDUCE-IT trial, according to Laffin. A similar study using AstraZeneca’s Epanova (omega-3-carboxylic acids), is slated to be completed by the end of 2019.

Bempedoic acid from Esperion, a once-daily, oral therapy is a first-in-class, non-statin, targeted therapy designed to inhibit cholesterol biosynthesis. Bempedoic acid reduces LDL by 15% to 20% and is currently in clinical trials to see if this decrease in LDL results in less strokes and heart attacks, according to Laffin.

Inclisiran from The Medicines Company is an investigational medication designed to inhibit the synthesis of PCSK9 protein in hepatocytes, thereby reducing LDL-receptor turnover and lowering plasma LDL-C. Initial study results show patients with a 52% reduction in cholesterol levels six months after their first injection of inclisiran, according to Harrington. She says that phase 3 trials have a scheduled completion date in the third quarter of 2019. “Time will tell how much this treatment will cost and how the insurance companies plan to help their patients have access to these treatments,” she says.

“The future of these new treatments might be a little brighter than in previous years as the AHA and the American College of Cardiology (ACC) just released new cholesterol managements guidelines in November 2018,” says Harrington. “For now, insurance companies will continue to see statins as first-line medication therapy in control of cholesterol; however, there are evidence-based guidelines from trusted institutions that could change the way insurance companies view these medications.”

Managed care organizations and payers will have to decide how to prioritize drugs and treatments for cardiovascular disease, including hyperlipidemia, while maintaining reasonable costs, Laffin says.

“The hope would be that increased availability of therapies to reduce LDL and triglycerides results in more comparative effectiveness studies and more competitive pricing from drug companies,” says Laffin. “It may also encourage payers and pharmaceutical companies to think outside the box when it comes to paying for novel therapies, including outcomes-based contracts or other strategies to align incentives for the patient and provider, insurer, and payer.”

, is a staff pharmacist at Southwest General Health Center, Middleburg Heights, Ohio.

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” from the CDC, an estimated 30.3 million Americans had diabetes in 2017, 7.2 million of which were undiagnosed. Approximately 5% had type 1 diabetes and the remaining 95% had type 2 diabetes. Over the last 20 years, the number of adults with diabetes has more than tripled, and the total direct and indirect estimated cost of diagnosed diabetes in the U.S. in 2012 was $245 billion.

“Diabetes is the highest traditional overall drug spend category for commercial, Medicare D, and Medicaid clients; and among all drug categories, only autoimmune has a higher drug spend,” says April Kunze, PharmD, senior director, clinical formulary development and trend management strategy, Prime Therapeutics.“Given the prevalence and the opportunities where diabetes care can go wrong, it can be an ideal area connected to outcomes-based contracts,” explains Mark Ginestro, a principal from 

. “The proper management of the condition can lead to major savings in overall medical costs.”

While there are some exciting promises in the pipeline, recent activity has cast doubts on that pipeline’s future. The FDA recently denied approval for the investigational drug Zynquista (sotagliflozin, Sanofi and Lexicon Pharmaceuticals) for type 1 diabetes.

Zynquista works by inhibiting both sodium-glucose cotransporter 2 (SGLT2), a transporter responsible for most of the glucose reabsorption performed by the kidney, and sodium-glucose cotransporter 1 (SGLT1), a transporter responsible for glucose and galactose absorption in the gastrointestinal tract.

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The agency issued a Complete Response Letter (CRL) in March, following an eight to eight vote by the FDA’s advisory committee in January in favor of the drug’s benefits outweighing its risks.

“Given the advisory committee’s vote it is not entirely surprising that the FDA has issued a CRL for the Zynquista New Drug Application (NDA),” Kunze says. “Other SGLT2 inhibitors are being studied for use in type 1 diabetes. Currently, SGLT2 inhibitors are approved for the treatment of type 2 diabetes.”

Farxiga (dapagliflozin, AstraZeneca), one of the SGLT2 inhibitors currently approved for type 2 diabetes, was recently approved for type 1 in Europe and is currently undergoing studies in the U.S.-but Zynquista’s rejection has cast doubts on its future in the United States.

SGLT2 inhibitor manufacturers are also studying overall health outcomes, such as major cardiac events and sub-populations within diabetic patients, including those with chronic kidney disease or heart failure, to show potential benefit and expand labeled indications, according to Kunze.

Technology also has an important role to play, with wearable devices, such as continuous glucose monitors (CGMs) that aid in the diagnosis, treatment, and self-management of diabetes. Ginestro also says that medical device makers have introduced different variations of the “artificial pancreas,” an automated insulin pump with a CGM for management of patients with type 1 diabetes.

As far as additional tech innovations beyond the artificial pancreas, more digital tools are being introduced to help with the diagnosis, management, and treatment of diabetes.

“That can come from patient education materials being tied to smartphones, which can help in preventive care for pre-diabetes or helping patients manage the condition,” says Ginestro. “Another opportunity is tied to using tech to connect the doctor or patient to warn of elevated A1c levels or blood sugar readings to engage a patient to prevent a trip to the emergency room. The use of predictive analytics can also be applied to stratify patients by risk so the ones most vulnerable to repeat hospitalizations can get the help they need.”

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With remote patient monitoring now being reimbursed by CMS, Ginestro expects more players to emerge in proactive health management.

“We expect to see more type 2 diabetes patients opting for use of CGMs and other monitoring devices,” says Ginestro. “We can even foresee the broader consumer community using CGMs when they may be deemed pre-diabetic or even for those who are simply health-conscious consumers.”

The demographic of tens of millions of pre-diabetics and the obesity epidemic mean there will be no shortage of patients, according to Ginestro. “Medications are aimed at making diabetes management easier with longer acting medications and technology is helping with the management of these conditions and addressing unmet medical needs,” he says.

“Given the increasing drug trend and the variety of medications available, pharmacy benefit managers will be looking closely at preferred product opportunities to help manage spend,” says Kunze. “In addition, payers will be looking for the real-world experience to match the clinical trial outcomes.”

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Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that characteristically affects the joints of the hands and feet, causing inflammation, swelling, pain, and progressive destruction of articular structures. RA affects about 1% of the population; onset may occur at any age but most often occurs between ages 35 and 50 years, according to 

“The main treatment goals with rheumatoid arthritis are to control inflammation, relieve pain, and reduce associated disability,” said Julie Rubin, director of clinical services, 

. “Treatment usually includes medications, occupational or physical therapy, regular exercise, and in more extreme cases, surgery to correct joint damage.”

 include nonsteroidal anti-inflammatories (NSAIDs) and steroids to help reduce inflammation, and disease-modifying anti-rheumatic drugs (DMARDs). “Methotrexate is the main therapy in the class of DMARDs but others include hydroxychloroquine, leflunomide, and sulfasalazine,” says Rubin.

Management and treatment strategies of RA has evolved over the last two decades due to the advent of biologics. Enbrel (etanercept, Amgen) was FDA approved in 1998, becoming the first biologic indicated for the treatment of RA. Since Enbrel, several other biologic medications have been approved for treatment of RA including Remicade (infliximab, Janssen), Humira (adalimumab, AbbVie), and Rituxan (rituximab, Genentech).

“Many of these drugs can be expensive, even with healthcare or Medicare coverage,” says Ashraf Shehata, advisory principal at KPMG and a member of the firm’s 

. “Higher out-of-pocket costs can be a compliance issue for patients and the high cost of these drugs tend to front load that burden on patients early in the year.”

 (tocilizumab, Roche), an interleukin-6 (IL-6) receptor antagonist.

 January 2010 for the treatment of moderate-to-severe RA in patients who have had an inadequate response to one or more DMARD. Actemra was originally developed as an intravenous infusion followed by a subcutaneous formulation approved in 2013. Most recently, a prefilled autoinjector (ACTPen) was approved in November 2018 and is expected to be available early this year.

 Intravenous solution: $131.04/mL; prefilled syringe (162 mg/mL): $1,186.66.

(tofacitinib, Pfizer), a JAK [Janus kinase] inhibitor.

 November 2012 for the treatment of moderate-to-severe RA in adults who have had an inadequate response to, or are tolerant of, methotrexate. In February 2016, Xeljanz XR became the first once-daily oral JAK inhibitor for the treatment of RA and Xeljanz is the only JAK inhibitor included in the most recent American College of Rheumatology 

 Xeljanz XR 11-mg tablet: $164.83/tablet, Xeljanz 5-mg or 10-mg tablet: $81.91/tablet.

(sarilumab, Sanofi and Regeneron), an IL-6 receptor antagonist.

 May 2017 for the treatment of moderately to severely active RA in adults who have had an inadequate response or intolerance to one or more DMARD. Kevzara comes as a prefilled syringe or auto-injector and is dosed every two weeks as a subcutaneous injection, which can be self-administered.

 Kevzara (150 mg/1.14 mL, 200 mg/1.14 mL): $1,552.63/mL.

(baricitinib, Eli Lilly), a JAK inhibitor.

 June 2018 for the treatment of adults with moderate-to-severe RA who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.

“There are a fair number of alternatives to help patients manage this condition,” says Shehata. “The biologic drugs are expensive, but they help keep the condition in check and could help avoid surgeries and disability costs.”

“Biosimilars could take some of the sting from the costs of RA drugs and several are on the market,” says Shehata. “Health plans need to consider whether the convenience of JAK inhibitors, which are administered orally, adds more value than the savings from injectable biosimilars.”

(etanercept-szzs), biosimilar to Enbrel (etanercept, Amgen), but not interchangeable with Enbrel.

August 2016, but U.S. launch is unknown due to patent disputes

(adalimumab-adbm), both approved biosimilars to Humira (adalimumab, AbbVie).

 Amjevita, September 2016, but under a settlement with AbbVie will not be marketed until 2023. Cyltezo, August 2017, but U.S. availability is currently unknown due to ongoing patent litigation.

(infliximab-dyyb), bioimilar to Remicade (infliximab, Janssen).

 Reconstituted 100-mg intravenous solution: $1,135.54/each.

 (AbbVie), an investigational, oral, JAK-1 selective inhibitor.

 Manufacturer submitted new drug application (NDA) to the FDA on December 20, 2018 for the treatment of adults with moderate-to-severe RA based on results of the SELECT phase 3 RA program studies.

(R-Pharm), an investigational, subcutaneous, IL-6 antagonist

 Currently in phase 3 studies to assess efficacy and safety in patients with moderate-to-severe RA (CREDO-4); estimated study completion date: November 2021.

 (Gilead and Galapagos), an investigational, oral, JAK-1 selective inhibitor

 Currently in a long-term extension study to assess the safety and efficacy in patients with RA (FINCH-4); estimated completion date: May 2022.

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Author | Erin Johanek, PharmD, RPh

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