AstraZeneca is developing an investigative anti-eosinophil monoclonal antibody benralizumab that can be administered subcutaneously in an at-home setting.
Drug development in the severe asthma space mirrors an industrywide move toward high-dollar targeted drugs, but so far progress is proving divisive. On one side, patients and physicians are basking in the glow of new life-altering solutions. On the other, innovation has given rise to payer blockades and out-of-reach price tags.
Patients with mild to moderate forms of the disease are relatively well served by current treatment options. However, there is a growing need for treatments that achieve control in those with severe asthma. While just less than 20% of patients with asthma have severe and uncontrolled forms, costs associated with hospitalizations due to acute exacerbations are responsible for roughly 75% of the $56 billion annual cost of asthma in the U.S.
Monoclonal antibodies designed to target the cells and pathways that cause asthma-associated allergic inflammation, including IL-5 inhibitors, are angling to upset the long-held small molecule approach to severe forms of the disease. “Biologic therapies provide us a way to not only treat the symptoms of the disease, but also the underlying disease itself,” explains Pamela Karas, U.S. respiratory biologics marketing lead at AstraZeneca.
Xolair (omalizumab), co-promoted by Genentech and Novartis, was the first biologic to snag approval for moderate to severe persistent allergic asthma in patients aged 12 and older. More than a decade later, Teva won FDA approval for Cinqair (reslizumab) to treat severe asthma with eosinophilic inflammation, just months after GlaxoSmithKline’s Nucala (mepolizumab) was approved in the same space. For patients with severe asthma, these treatments work in unison with other medications to maintain adequate control of the disease.
WHO HAS THE EDGE?
With minimal differences in safety and efficacy, market share is still somewhat up for grabs. However, many analysts say GlaxoSmithKline’s subcutaneous formulation and its roughly six-month head start gave the company an edge over Teva.
Either way, it’d be wise to keep an eye on expanded indications for Xolair as well as late-stage market challengers from AstraZeneca, Sanofi/Regeneron, and Novartis. While small molecules currently account for 98% of the products available in the asthma space, GBI Research found the pipeline consists of 12% mAbs and 17% non-mAb biologics.
The industry is beginning to recognize that hard-to-treat asthma patients have different needs that cannot be met by conventional treatments alone. As such, late-stage biologics manufacturers are pursuing two fundamental strategies to establish a commercial foothold. Companies are investing in unbranded efforts to highlight the acute need to treat more severely afflicted patients as well as attempting to capitalize on unique mechanisms of action (MOAs) to position products as innovators in individualized care.
“Biologics are working. The shots are well tolerated and patient satisfaction is high,” explains Dr. Bernard Kinane, chief of the pediatric pulmonary unit at Massachusetts General Hospital, who refers to the new treatment option as a quantum leap in asthma care.
With monthly in-office administration of biologics, physicians have noted improvements in disease management. “Inhalers are often used incorrectly at home, which limits their effectiveness. Also, the patient burden is significant, requiring several doses a day,” Kinane adds.
However, payers aren’t always reading from the same manual. “Drug manufacturers are pushing for targeted drugs, but they’ll have a tough time convincing payers,” notes Andrew Lyle, director of business development at specialty pharmacy Curexa Pharmacy.
Theoretically, using biomarker levels to identify the patients most likely to respond to treatment gives patients and payers greater confidence in deciding the most appropriate treatment. Alas, payers don’t necessarily agree.
“For payers, it’s a double-edged sword because it addresses the patient subpopulation that disproportionately drives the cost of asthma care but also provides pricing power to the manufacturer,” says Trinity Partners’ engagement manager Steve Yonish.
While Teva’s head of global respiratory medicines, Sven Dethlefs, acknowledges that economics drives some choices, he insists it’s not the only factor. “Look at oncology. The payers are more and more interested in the rationale for prescribing a particular therapy and are moving away from the trial-and-error patient-selection approach,” he explains.
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Perhaps there are lessons to be learned from Xolair. A long time passed between its 2003 approval and the addition of chronic idiopathic urticaria to its list of indications in 2014 and the expanded asthma age range in 2016.
“Xolair was breaking down barriers and narrowing the disease state far before everyone else,” Lyle notes. “But it was so early to market that people didn’t know what to do.”
As it stands, asthma biologics are not popular with formularies. Even when they are covered, they’re subject to a long list of requirements. And with some asthma biologics costing patients roughly $30,000 annually, manufacturers are focusing on cost-effectiveness studies to prove their value.
“These drugs will no doubt gain better formulary placement once cost studies come out,” Lyle predicts. “Asthma biologics could follow in the footsteps of what Gilead accomplished in the hepatitis C market: Pay upfront to save money in the long run.”
HCPS IN PLAY
The market has room for more biologics if manufacturers can better justify why their products deserve to be added to the arsenal of HCP treatments. “Companies may not find key positioning if they cannot combine science and clinical outcomes with the ability to identify the right patient pool,” Dethlefs explains.
Targeting asthma subtypes can help products entering the pipeline stand out from competitors. For example, marketed IL-5 inhibitors Cinqair and Nucala take aim at eosinophils, but Sanofi/Regeneron’s dupilumab — in trials for uncontrolled persistent asthma — targets the messenger proteins of the eosinophils, not the eosinophils themselves.
Others are making early investments in the interleukin-33 (IL-33) pathway, a protein that affects inflammation. GlaxoSmithKline acquired global rights to Johnson & Johnson’s Phase I biologic CNTO 7160, and Genentech struck a similar deal with Amgen, while AnaptysBio has an early competitor in the works.
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AstraZeneca’s investigative anti-eosinophil monoclonal antibody benralizumab is attracting attention for its ability to be administered subcutaneously in an at-home setting.
“The first product to offer patients the ability to self-administer at home could drive separation from the pack,” Yonish notes.
Kinane takes this thinking one step further, predicting that biologics will eventually become oral medications. In response to demand, Novartis is investigating an oral DP2 receptor antagonist, fevipiprant, for patients with severe asthma stratified by blood eosinophils (see Clinical Corner, below).
GlaxoSmithKline’s asthma.com is a patient disease-education resource replete with an asthma control test and a self-care kit to advance the knowledge of all asthma patients.
In the meantime, manufacturers must conduct biologic profiling to produce a more personalized approach to asthma. “We need to identify the targets,” Kinane continues.
And a big part of that is educating the masses. “The communications goal of having physicians and patients associate severe asthma with either allergic or eosinophilic status is prominent in many current campaigns,” Yonish says.
Teva focuses much of its marketing for Cinqair on the HCP audience. “HCPs need to understand the biomarker and the patient-selection process and have confidence in the drug itself,” Dethlefs explains. “Because it’s a new drug in a new paradigm, we talk about the science first.”
GlaxoSmithKline’s asthma.com is a patient disease-education resource replete with an asthma control test and a self-care kit to advance the knowledge of all asthma patients. GSK also has a plan for capturing patients who don’t just stumble upon the site with a Google search.
“We’re operating in an increasingly digitally savvy world,” says Gene Rhie, head of U.S. marketing for GlaxoSmithKline’s asthma therapeutic area. “Social media, branded product websites, and disease- education resources are all part of an ecosystem that helps us connect with the patient journey,” he explains.
Marketers are aiming to carve out a point of differentiation with brand recognition. For instance, GSK’s campaign for Nucala sported the tagline, “A lot of people have asthma. But my asthma is different.” The website introduces patients to the potential cause of severe asthma and discusses the use of a blood test to determine eligibility for the biologic.
Marketers are excelling at uncovering the information and tools patients lack in their quest to feel better.
“Manufacturers have focused on developing a deep understanding of the patient journey and the many obstacles these asthma patients face,” explains Jerry Lee, VP/group director of science and medicine, Digitas Health.