Several studies on omalizumab (Xolair), currently manufactured by Novartis through a partnership agreement with Genentech, recently presented at the 2017 Annual American Academy of Allergy, Asthma, and Immunology (AAAAI) meeting in Atlanta, Georgia, demonstrated why biologic therapies are considered by many to be the “future” of care.
Omalizumab, an injectable medicine for patients 12 years and older for treating severe-to-persistent allergic asthma not controlled by inhaled corticosteroids (ICS), was approved by the FDA in 2003 only for asthma. The indication was modified several times over the next decade, and included a warning of “slightly higher risk of heart- and brain-adverse events,” which was added in September 2014. While the warnings may have changed, the uses for this flexible biologic drug have clearly only begun to be discovered.
“Despite the availability of omalizumab since 2003, utilization trends have not been previously described,” observed 1 research team, headed by Matthew Rank, MD, a physician at the Mayo Clinic in Scottsdale, Arizona. The team identified 8545 patients who used omalizumab between 2003 and 2015. They excluded certain conditions in order to prevent “censoring based on insurance coverage,” and noted that individuals starting on the biologic peaked in 2005 at 9.56 new users per 100,000 insured people and declined to 5.22/100,000 in 2012. In 2015, that number had climbed back up to 12.13/100,000, although 59% of those users stopped using the drug after less than a year.
The increased usage and relatively short duration of use could be due, in part, to aggressive marketing on the part of Genentech, which forecasters predicted at the end of Q1 2016 would own about 40% of 2016’s “top 10 new drugs in peak projected sales,” in large part due to its biologic and biosimilar research. Back in the 1990s, Genentech “officially committed to oncology” in the words of then-CEO Arthur D. Levinson, PhD, and that decision led the company toward biopharmaceutical research that, including breakthrough treatments for multiple sclerosis and, eventually, to omalizumab, which was a blockbuster drug in 2014. Genentech and Novartis ultimately endured a nasty scandal when whistleblowers accused them of marketing omalizumab directly to healthcare providers for wide-ranging uses instead of the narrow window of use prescribed by the FDA. The fact remains that omalizumab usage spiked and has remained high since.
Perhaps more exciting than the usage study was a study indicating that baseline blood eosinophil levels and asthma exacerbations could be reduced in children with moderate-to-severe allergic asthma through use of omalizumab. This is particularly intriguing since FDA restrictions on using the drug in children under 12 have been problematic for both drug manufacturers and physicians wishing to treat pediatric patients who are not responding to other therapies, including ICS, with omalizumab. The researchers, led by author Stanley Szefler, MD, a physician at the Children’s Hospital in Colorado and a professor at the University of Colorado School of Medicine in Aurora, Colorado, conducted a 24-week inhaled steroid dose-stable phase of a double-blind, randomized, controlled trial in children 6 to 12 years of age with “inadequately controlled, moderate-to-severe, allergic asthma.” They reported, “Clinically significant asthma exacerbation rates were reduced by 31% (P = .007) with omalizumab versus placebo. The study not only demonstrated a pediatric usage that might be beneficial to a younger age group, but also provided a method for physicians to predict how younger patients might respond to the treatment, since children with elevated baseline eosinophil counts ≥300µ showed a “significantly greater response” to the drug compared with placebo, while children with lower baseline eosinophils had “nonsignificant reductions.”
Finally, another group led by Shaun Kilty, MD, a physician in the University of Ottawa Hospital’s Otolaryngology-Head and Neck Surgery, presented evidence that omalizumab treatment “provided significant improvement in every major clinical symptom of chronic rhinosinusitis (CRS),” although the group emphasized that “a well-designed clinical trial is needed to further assess the efficacy and safety” of the treatment. The group evaluated 25 patients diagnosed with CRS and 5 control patients who would have qualified for the study but could not get insurance coverage for the treatment. The patients were treated for a mean duration of 19 months, and 76% had CRS with polyps while 33% had aspirin exacerbated respiratory disease. “The omalizumab therapy provided a mean overall symptom improvement of 69.5%,” Kilty reported, noting that this meant patients who received the omalizumab treatment experienced less facial pain, fewer nasal obstructions, and improvements in rhinorrhea and olfaction, while the control group, which also improved overall, experienced far less improvement.
These 3 studies, in conjunction, clearly demonstrate why biologic and biosimilar drugs represent such promise for pharmaceutical companies and for the fields of asthma, allergy, and immunology. With biologics and monoclonal antibodies (mAbs) in particular making up nearly a fifth of the asthma pipeline alone, according to business intelligence firm GBI Research, these drugs often represent new options to patients with the most sensitive immune systems who have high levels of intolerance for many of the more “traditional” pharmaceutical options. One GBI analyst observed of the firm’s data, “Drug developers are looking to follow the example of Xolair by developing highly-targeted biologics and mAbs aimed at specific patient subtypes with the hope of benefiting previously underserved patients and generating strong revenues.” Another benefit of this strategy is that biologics often target pathogenesis that is relevant to multiple conditions, thereby opening up new uses for drugs in the future, as is currently the case with omalizumab.