Brand of the Year: Humira

Pharmaceutical Executive | Ben Comer

Despite an already crowded market, everyone is keen on developing new medicines to combat autoimmune diseases, like rheumatoid arthritis (RA), psoriasis and Crohn’s disease. The anti-TNFs – Remicade, Enbrel, and PharmExec’s Brand of the Year, Humira – are the towering giants in the space. Their combined sales exceed the GDP of Afghanistan. Even with patent expiration beginning in early 2017, analysts are predicting that Humira’s sales will surpass Lipitor’s as the top-selling drug ever. For patients, the anti-TNFs can mean the difference between a crippling disability, and a relatively normal existence.

Humira continues to grow, a decade after launch. Abbott reported a global growth rate of 21.1% for Humira, with total sales at $7.9 billion, for 2011. On the earnings call, Abbott execs touted the biologic drug’s breadth of indication, strong long-term safety and outcomes data, including a record of superior clinical efficacy, and a deft managed market performance. Jeffrey Stewart, Abbott’s VP of U.S. proprietary pharmaceuticals, says the fundamental talents at Abbott revolve around anticipating the market, and then executing on strategy. “When you think about the three biggest indications – RA, psoriasis, and Crohn’s – our indication set is the closest match to the market,” says Stewart.
 New indications are in the forecast. At JP Morgan’s 30th Annual Healthcare Conference last month, Thomas Freyman, Abbott’s EVP finance and CFO, described Humira as a “cornerstone” of the proprietary pharma business, one he expects to contribute “strong and sustainable growth” for the new proprietary pharmaceuticals business. (Abbott announced plans to split its drug and medical device products into two separate businesses, more on this in the full-text February feature). Freyman said “low global penetration rates for biologics create a significant opportunity to drive longer-term sustainable growth…we’re focused on expanding the anti-TNF market, and the Humira patient base, as well as improving patient adherence.” Indeed, Humira is “growing faster outside of the U.S., says Barbara Ryan, managing director, Deutsche Bank Securities.

Strength in Numbers

One of the most valuable cards in Humira’s deck is the numbers, in the form of long-term clinical studies. By extending clinical trials, Abbott has been able to link data to safety. “In RA, we’re proud to be able to highlight eight years of showing that the joints are stable, that the joints don’t deteriorate over time,” says Stewart. 

That eight-year period, “unique to Humira,” allows “our representatives to frame out why Humira might be the best option for patients,” according to Stewart. In psoriasis, there have never been head-to-head trials between Amgen/Pfizer’s Enbrel and Johnson & Johnson’s Stelara, but “if you look at the perception among doctors, and you look at the market research, the skin clearance that we see in our pivotal trials – the ability to clear plaque psoriasis from 75% of the body – it’s pretty much universally viewed as very impressive efficacy data,” says Stewart. In 2011, Humira became the new prescription and the total prescription market share leader in dermatology, and gained almost three share points, says Stewart. “The market is rewarding us for our profile and our ability to communicate the Humira data.”

Fear Factor

Like the other anti-TNFs, Humira is not without serious potential side effects. The class carries FDA’s sternest safety warning – the Black Box – which can be hair-raising for patients. Virginia Ladd, president and executive director of the American Autoimmune Related Diseases Association (AARDA), says patients have a real “fear factor” when it comes to the anti-TNFs. “Lymphoma, they hear that, they hear cancer in the advertisements, life-threatening infection, tuberculosis…you have to be pretty brave,” she says. 

Like other drug companies in the space, Ladd says Abbott “does an excellent job [educating patients]; they have websites, they have webinars, and all kinds of things that are patient-friendly and helpful.” However, a forthcoming study from the AARDA suggests that pharmaceutical companies aren’t too high on the list of trustworthy sources for information. Ladd says physicians are partly to blame for this distrust. Symptoms like fatigue and joint pain, and the fact that RA in particular affects women disproportionately, makes the diagnosis process frustrating for many. “Over 40% of the patients surveyed were told that they were chronic complainers or too concerned with their health,” says Ladd, citing the study. When patients do finally receive a diagnosis, and the doctor hands them a script for an anti-TNF, the patients “see the ads, and there’s a level of mistrust to begin with,” says Ladd. Despite that fact that biologics like Humira “represent a real advance in the treatment of autoimmune diseases,” patients don’t always understand the risks of not beginning treatment, even though early diagnosis and drug intervention can prevent crippling and disability. 

Cost Conundrum

Even with insurance, access to Humira requires a “very rigorous” prior authorization process, says Stewart. To expedite the process, Abbott created a “reimbursement hub that enables doctors and patients to call and find out if a given insurance benefit will cover Humira,” Stewart says. Even so, a growing number of insurance plans have substituted flat-rate co-pays with co-insurance, which requires the patient to pony up a percentage of the total cost. Stewart estimates that 20% to 25% of commercial plans now use co-insurance, leaving patients on the hook for a larger chunk of the cost. 

To help patients hurdle the cost barrier, Abbott’s Humira Protection Plan offers financial assistance to those who need it. If a patient is employed and has a prescription drug benefit, Abbott can “reduce your co-pay to $5 a month,” according to the program website. Unemployed and/or uninsured patients may also be able to get the drug at no cost, through the Abbott Patient Assistance Foundation, assuming they meet the requirements. 

By law, Abbott can’t assist patients under Medicare Part D, and the brand’s market share is lower under classic Part D. “We’ve hypothesized that a lot of that is due to the varying incentives of a medically reimbursed infusion,” which is covered under Medicare Part B, and “which often has no co-pay immediately and then is very likely to hit the donut hole,” says Stewart. The financial incentives for physicians around medically reimbursed agents, particularly infusion versus subcutaneous injection, and the corresponding Medicare benefits, contain “a lot of sensitivities,” says Stewart

New Indications

Six new indications are on the docket for Humira: hidrandenitis suppurativa (a fulminating inflammatory skin disease); uveitis (an eye inflammation that can lead to permanent vision loss); axial and peripheral spondyloarthropathies, or SpA (two indications covering a group of wide-ranging inflammatory diseases); ulcerative colitis (an inflammatory bowel disease); and pediatric Crohn’s disease. The FDA is expected to weigh in on the ulcerative colitis indication this year, although “we wonder to what extent it’s already being used off-label,” says Deutsche’s Ryan. The new indications represent a “substantial opportunity” for Humira, and “a lot of relief for patients,” says Stewart. 

Stewart is cool on the next-generation JAK inhibitor class, of which Pfizer’s tofacitinib is the closest to market. Regarding the twice-a-day JAK inhibitor, Stewart says there isn’t anything new in terms of safety and efficacy. “If you look at the data, the market has moved beyond [American College of Rheumatology] scores”—which measure change in RA symptoms—“and it’s really focusing now on radiographic inhibition, and there’s some interesting data” related to tofacitinib dosing and radiographic inhibition, says Stewart. While other marketed products nip at the heels of Humira, and newcomers hope to pick away at Humira’s share, Abbott will focus on managing its competition, at least until the patent expiries set in. Stewart says Humira has “strong patent protection through early 2017 in the U.S., and early 2018 in Europe,” in addition to “numerous process patents that extend well beyond that time frame.”

Origins

Abbott CEO Miles White was something of a soothsayer when it came to Humira. When Abbott announced that it would acquire BASF’s pharmaceutical business, known as Knoll, in December 2000, Abbott’s stated goal was to “broaden its global infrastructure, acquire late-stage and marketed products, increase its pharmaceutical R&D spending significantly, and access leading monoclonal antibody technologies,” according to the issued press release at the time. 

The last goal was the crucial one; Knoll’s monoclonal antibody, called D2E7, would become Humira. In the release, White said the acquisition would help to build Abbott’s footprint in Europe and Japan, and called D2E7 a “high-potential product.” High potential indeed, considering Abbott paid $6.9 billion for BASF/Knoll, and Humira earned nearly $8 billion last year alone. 

The acquisition has had no small impact on the pharma sector and its direction, and hundreds of thousands of patients with severe autoimmune diseases have used Humira to improve their quality of life. As biologic drugs become increasingly prescribed and used, education for physicians—but especially patients—will be critical. In 2011, Humira sales grew in all of the “big three” indications, due in no small part to patient communications, says Stewart. “We were really able to talk to the consumer like never before in 2011 … there was significant push in disease awareness, mass-media campaigns, and branded Humira commercials.” Given the low penetration rates, it makes sense to reach out to patients with educational messaging. “I’m very proud of the way we’ve handled that, and I think it has aided both patients and the performance of the brand,” he said.