Autoimmune drug pipeline: What health execs should watch

With as many as 80 autoimmune diseases potentially attacking all parts of the human body, it should be no surprise that spending on treatment for these conditions rose 28%, to $30.2 billion, between 2014 and 2015, according to an IMS Institute for Healthcare Informatics report released last May.

Among the top 15 therapy classes ranked by per member per year spend, inflammatory conditions top the list at $118.21, followed by diabetes at $108.80, according to Express Scripts’ 2016 Drug Trend Report, released in February. Among the top 10 specialty drugs, four products are for inflammatory conditions. The top two are Humira (adalimumab) and Enbrel (etanercept). Total trend for this class was 26.4%. Employers paid an average of $3,587.83 per prescription for inflammatory drugs.

Autoimmune diseases run the gamut from more well-known conditions such as rheumatoid arthritis, inflammatory bowel diseases and psoriasis to other conditions such as Graves’ disease and Myasthenia gravis, affecting the thyroid gland and nerves, respectively.

New drugs for RA, psoriasis, type 1 diabetes and Crohn’s disease-some recently approved and others coming down the pipeline-could have an impact on the industry in both their anticipated clinical results and price tags.

Rheumatoid arthritis

Nicolosi

“The biggest thing we are waiting for are biosimilars for Humira and Enbrel, the market leaders, but patent litigation is delaying bringing Amjevita [adalimumab-atto], a Humira biosimilar, and Erelzi [etanercept-szzs], an Enbrel biosimilar, to market,” says John Nicolosi, senior vice president and chief clinical officer, healthcare, Highways Rx, a pharmacy benefits manager. Enbrel and Humira, the market leaders, are priced at about $3,500 and $2,400 a month, respectively, setting the trend for other new drugs in the class.

Inflectra (infliximab-dyyb), a biosimilar for the well-known drug for RA, Remicade (infliximab), was approved in April 2016. It also faces patent litigation before it hits the marketplace. 

“Once it is made available, it is only projected to initially provide a 15% discount compared to Remicade,” says Nicolosi. “Although expected, this is much lower than the discounts seen for the Remicade biosimilar in Europe-about a 45% discount.”  

The impact on this drug will be largely dependent on its availability, cost and adoption within clinical practice. 

Nicolosi expects that biosimilars in general will lower costs by 15% because market leaders dictate costs. However, he holds out optimism for a growing number of new products with similar outcomes coming down the pipeline for RA-more than 10-as a means of stirring up competition and lowering costs.

Although Enbrel exploded the biologic therapeutic marketplace with its introduction in 1998, followed by other medications with different mechanisms of action that proved to be effective in inducing remission, Nathan Wei, MD, clinical director of the Arthritis Treatment Center and a rheumatologist in Frederick, Maryland, says this is an era of me-too drugs and those with different mechanisms of action are slow to follow the first to market in a category.

Gleason

Pat Gleason, PharmD, senior director of health outcomes, Prime Therapeutics, agrees with Wei that there is little differentiation among new autoimmune drugs and that they only add to expenses due to inflation and more utilization. He acknowledges that these drugs have been driving drug spend from 2012 to 2015 even though 25% of use falls under the medical benefit.

Three other drugs in the category could potentially pose threats for established drugs for treating RA: baricitinib, a JAK1 inhibitor, and sarilumab and sirukumab, both interleukin-6 receptors.

Baricitinib, administered orally once daily, is currently in development. Nicolosi says it will likely compete with Xeljanz and Xeljanz XR (tofacitinib citrate), which are existing products on the market with similar administration and mechanism of action. Baricitinib’s Prescription Drug User Fee Act (PDUFA) date that spells out deadlines by which the FDA must review new drug applications was slated for April at press time.

However, there have been serious safety concerns with baricitinib, which include major cardiovascular events and malignancies that have added some significant hesitation with this product, says Nicolosi. “This could be another option for individuals who had an inadequate response to other treatment options, but I don’t anticipate it having any significant impact on the treatment algorithm for RA,” he says. “Despite the safety concerns, I have read the projected U.S. annual sales for baricitinib could range from $1 billion by 2020 to $2.9 billion by 2025.”

The arrival of sarilumab also has been detained on its journey to the marketplace but in this case, for manufacturing concerns. Its original PDUFA date has come and gone and is now set for mid-2017.

Sirukumab is currently in phase 3 trials and has shown mixed results.

Wei adds that people on JAK inhibitors can also have an increased risk of certain cancers, high cholesterol and triglycerides, liver function abnormalities, kidney dysfunction and a drop in white and red blood cell counts. He expects the newer drugs in the pipeline to be safer.

He says some of his patients who are controlling their RA have chosen to go the non-traditional route of trying herbal remedies to avoid toxicity. “But if they are not in remission or even close, I try to steer them to the conventional route.”

Next: Type 1 diabetes

Type 1 diabetes

Nicolosi says most new products for type 1 diabetes are combinations and repackaging of existing products. Changes are primarily seen in less frequency or oral drugs versus injections.

Glatt

Aaron Glatt, MD, chairman, Department of Medical and Hospital, South Nassau Communities Hospital, Oceanside, New York, agrees that there is limited activity among drugs for type 1 diabetes, saying that most of the new medications are me-too drugs, and those in the pipeline are not expected to be major players.

A procedure in the works described by the American Diabetes Association (ADA)-although experimental-is transplantation of islet cells from a pancreas of a deceased organ donor that are purified, processed, and transferred into another person. “It could be a game-changer,” Glatt says.

Patient testing has started on a stem cell treatment that could offer a cure for type 1 diabetes. The first-of-a-kind treatment reported by the ADA turns stem cells into insulin-producing ones.

Crohn’s disease

RA drugs-Humira, Remicade and Cimzia (certolizumab pegol)-are crossing over as  treatments for Crohn’s disease, as well as plaque psoriasis, Nicolosi says. Although injections such as Humira and Cimzia and an infusion for Remicade can be more expensive than oral drugs, he sees an increase in the use of injectables because they are a more effective option for treating severe Crohn’s and have proved to work better than orals that have been tested and failed in some cases.

It is common to start individuals with Crohn’s taking an immunological agent on a high dose initially (loading dose or starter kit) and then stabilizing them on a lower maintenance dose, Nicolosi says; however, this triggers higher costs. For example, when using Humira, patients typically start treatment taking 160 mg on day one and then 80 mg on day 15. After the initial dose, patients are frequently stabilized on 40 mg every other week as their maintenance dose. 

Ladd

Virginia Ladd, president and executive director of the American Autoimmune Related Diseases Association, is a firm believer in moving away from drugs for Crohn’s and taking a closer look at the human microbiota consisting bacteria, fungi, archaea and viruses, many of them in the gut.

“We need a balance of bacteria in the body so it is important to normalize or regulate them,” she says. “Medications have done that, but microbiome treatment is much less expensive.”

Psoriasis

Stelara (ustekinumab), a monoclonal antibody approved in 2009 for the treatment of plaque psoriasis and approved in 2013 for psoriatic arthritis, set the pace for a new class of drug-interlukin-17 (IL-17) inhibitors. Stelara has since shown effectiveness in treating Crohn’s disease and was approved for that use in 2016.

Three IL-17 receptor drugs for the treatment of plaque psoriasis and/or psoriatic arthritis built upon Stelara have entered the marketplace in the last two years: Cosentyx (secukinumab) in 2015, Taltz (ixekizumab) in 2016 and Siliq (brodalumab) in 2017.  

Both Cosentyx and Siliq are subject to black box warnings; Cosentyx’s availability is restricted through the Risk Evaluation and Mitigation Strategies program (REMS), while Siliq faces a risk mitigation marketing program restriction.

In November 2016, Janssen submitted its application to the FDA for guselkumab, an IL-23, to treat plaque psoriasis.

What is expected to be the biggest game changer or perhaps even a blockbuster in psoriasis-related conditions is Dupixent (dupilumab) for atopic dermatitis (eczema), which is currently in phase 3 trials, Gleason says.

It is expected to be approved by the end of March but will come with a high price tag-$50,000 a year. “It should work better than adding more corticosteroids if patients cannot control their condition,” he says.

Mari Edlin, a frequent contributor to Managed Healthcare Executive, is based in Sonoma, California.