The immune globulin class has experienced frequent supply issues over the years, with a differing array of brands being available at any given moment. That unpredictability led to inconsistency in the use of products, which in turn contributed to the perception that the therapies are interchangeable. But while they may be similar, there are definitely differences among the agents.

Although the immune globulin market in the U.S. has “been mostly stable among large manufacturers the last two years,…supply issues have not been fully addressed,” says Melinda Haren, director of access strategies at The Zitter Group.

“This is a very, very undifferentiated market,” explains Haren. “Most prescriptions say, ‘IG’” rather than specifying a certain brand. The reason why, she says, was because of shortages (SPN 6/07, p. 1). So if a physician wrote “IG” instead of a brand, there was “no need to rewrite the script or redo paperwork” as would be needed if a brand was specified but wasn’t available.

“Payers have been unaware until fairly recently” of the IG market dynamics, Haren says. “They know IG is expensive, and they know the majority of use is off-label. From their perspective, there is no difference among agents.” However, “this is not actually true, but because these manufacturers have been fairly small, they have not had the opportunity or ability to do a lot of education with payers.”

Immune globulin is a blood plasma derivative, so its production depends upon plasma collection. “The manufacturing process for creating and purifying immune globulin is different” among the products, explains Stephen Cichy, president and CEO of Monarch Specialty Group, LLC. “Stabilizing agents used as adjuvants are all unique and different by brand,” although all of them are doing the same thing, which is helping stabilize the immune globulin that is delivering a protein that naturally occurs in the body.

As an analogy, Cichy compares the immune globulin class to soup. There are a lot of New England clam chowders available, for instance, and “all essentially use the same ingredients, but there are subtle differences among the brands.” The 10 approved products now available are different in terms of aspects such as their half-life, IgA content, sodium content and osmolarity, he says.

“All immune globulins are manufactured through a process where proteins are produced, refined and delivered through a special biologic process,” explains Cichy. “Any disruption to the manufacturing process and the supply chain…could be potentially disruptive” to the immune globulin marketplace.

Threat of Shortages Limited Contracting

According to Haren, that threat of disruption to the immune globulin supply has historically hampered manufacturers’ willingness to differentiate themselves from their competitors. But about 12 to 18 months ago, that began to change, as companies began approaching payers to assure them that their supply was stable and that they could be trusted to be able to provide the product.

However, Haren says, “in my opinion, they didn’t provide adequate support and education” about the immune globulin market. Manufacturers, she explains, can provide only a certain amount of immune globulin — they “can’t double that [manufacturing] capacity.” And there can be “a great deal of difficulty” in getting people to donate blood.

So potentially these firms may get a contract that they are not able to fulfill. But for some of the smaller manufacturers, “maybe the risk is worth it” because they rationalize that “the only way I will get market share is if payers force their members to get my drug. I’ll cross that [supply] bridge when I come to it,” she says.

“The majority of immune globulin in today’s marketplace is purchased through allotment” of the product to payers, Cichy notes. Companies are “granted access to products based on their dispensing history.…In any economic or manufacturing downturn, larger distributors are likely to be the first to gain access to product based on their dispensing status.”

Payers also need to understand that while many of the immune globulins are approved for the same indications, there are additional uses that maybe only one or two may have. But with relatively low usage of the products, there “doesn’t seem to be a solid understanding among immunologists” of the differences in immune globulin indications, says Haren. “A large immunology practice probably has 10 people” on immune globulin. The providers, she says, have “always had supply issues, so they’ve always prescribed ‘IG,’” rather than specifying a particular brand. And with most payers not having any utilization management of the agents, there often aren’t any edits in place to make sure a therapy is approved for the prescribed indication. In addition, off-label use of the product is widespread.

With such a small patient population, it’s hard to really determine how the products compare. And “if the immune globulin doesn’t work, the side effects are essentially the same” as those of many of the conditions that it’s being prescribed to treat, she says. “So is the drug not working, or is the disease getting worse?”

For payers, “the message they hear is that the supply line is stable,” says Haren. And plans are faced with the fact that “there is no place else to save money on the pharmacy side anymore.” A plan that signs a contract for a specific immune globulin that offers a 5% discount for preferring that brand potentially could “sometimes save upwards of $1 million or $2 million per year.” So if implementing such a program doesn’t impact quality, why not do it?

Payers want to approach the immune globulin class like they do the rheumatoid arthritis and multiple sclerosis therapeutic classes, Haren says — “very crowded marketplaces with limited” clinical differentiations. “But in this particular case, patients could end up suffering.”

What Happens if Shortage Recurs?

Although there is the potential for a market disruption to occur anytime, some payers may not have a process in place to deal with such a situation. “Payers in general don’t have contingency plans for something like that, especially with such a small patient population,” Haren says. “They wouldn’t have made the choice in the first place [to prefer a product] if they thought there was a risk” of a shortage occurring. “They’re trying to provide care to everyone” and keep costs down. “In this atmosphere, every dollar counts. At some point, we do not have unlimited resources and unlimited dollars.”

Prime Therapeutics LLC “will not contract with a company if they can’t guarantee we will get supply,” says Patrick Gleason, Pharm.D., the PBM’s director of clinical outcomes assessment. “Our contract guarantees supply.”

Stockpiling product, however, in hopes of maintaining supply is one response that should not be taken, maintains Amy Clarke, a clinical program manager at Diplomat. Because immune globulin “is a short shelf-life product,” hoarding is not a good approach. Instead, payers need to “prepare patients and physicians” for a potential disruption. “This is a volatile product. They may need to look at alternative products should a shortage occur.”

Updating the allotment method for the product also would be helpful, contends Hetty Lima, vice president of specialty infusion and rare diseases at Diplomat Specialty Pharmacy. If “grams of immune globulin would follow the patient, so the grams are attached to the patient and not the specialty pharmacy, we’d be in a much better spot.”

A strong pipeline could bring more options to the marketplace, notes Lima. The class, she says, has “tremendous growth potential. The pipeline is rich with new products and new devices to administer them.” Among these are prefilled patch pumps, which can be applied like a nicotine patch.

But because the agents are manufactured from human blood, obviously the amount of product varies. In addition, the supply could take a hit depending on whether the therapies prove useful in and gain approval for some additional indications.

The product is being studied as a potential treatment for Alzheimer’s disease, and if that condition is added to the label, “that will drive demand in the U.S. four-fold,” maintains Lima. “You’re going to see shortages developing. You only have as much immune globulin as you have people donating blood.”

She also points out the fact that some companies have closed some of their locations. So perhaps signs of the “beginnings of a constrained supply again” may already be appearing.

© 2012 by Atlantic Information Services, Inc. All Rights Reserved.

Learn about immune globulins and other specialty therapies in the drug pipeline in the Aug. 29 webinar Payer Strategies to Manage High-Cost Specialty Drugs Expected to Hit the Market Soon. Diplomat Specialty Pharmacy’s Atheer Kaddis, Pharm.D., and Bill Sullivan of Specialty Pharmacy Solutions will discuss the pipeline in light of emerging trends within the evolving specialty pharmacy space. Visit http://aishealth.com/marketplace/webinars to learn more.