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Darcee Strube offers an overview of the key issues and progress made in dermatology biologics.
Biologics have gained a foothold in dermatology, and growth in this area has been fueled by improving clinical outcomes. The dermatology market is expected to grow to $33.7 billion by 2022, and 37 percent of drugs currently in the pipeline are biologics, according to one 2016 report.
Nearing approval, Merck’s monoclonal antibody tildrakizumab is currently in review with the U.S. Food and Drug Administration (FDA) and could become the 12th approved biologic therapy for moderate to severe plaque psoriasis. Other biotechs are charting new territory: In March 2017, the FDA-approved Regeneron’s dupilumab (Dupixent) as the first biologic to treat atopic dermatitis. Biologics have been approved to treat other indications such as hidradenitis suppurativa, urticaria, and have been used off label to treat alopecia areata.
To be a prominent player in the market for dermatologic therapies, companies developing biologics must successfully navigate a series of significant challenges, including patient compliance, medication costs, and patient safety. What follows is an overview of these key issues and progress made.
Biologics are typically a third-line treatment option for patients who have not responded sufficiently to topicals and/or phototherapy. However, issues with patient compliance may prevent patients from receiving the full benefits of therapy. Patient compliance is impacted by how drug regimens are administered, e.g., a self-administered injection vs. in-clinic intravenous infusions. Frequency, dosage, need for monitoring, and safety concerns can also influence overall compliance. Noncompliance with treatment regimens may lead to adverse effects such as the formation of anti-drug antibodies.
To help ensure patient compliance for dermatology treatments, patient advocacy groups recommend a focus on goal setting. The National Psoriasis Foundation’s “Treat 2 Target” program provides a set of treatment goals for patients to use with their providers. The goals, published online in the Journal of the American Academy of Dermatology in November 2016, include doctor visits at three and six months after initial diagnosis or the start of new treatment to monitor progress with a target of one percent or less of psoriasis covering the body. The foundation also provides a treatment comparison chart to help patients and physicians make informed decisions regarding options.
Biologics can be more effective than topical therapies because they address underlying disease and inflammatory mechanisms rather than merely the symptoms. This has led to noteworthy improvements in patient outcomes, as outlined in a 2014 study which examined quality of life and mental health in psoriasis patients comparing biologic treatments to other modalities. The study concluded that patients treated with biologics saw a 52.2 percent decrease in General Health Questionnaire (GHQ-30) scores, as compared to a 24 percent and 17 percent decrease among systemic and topical treatments, respectively. This data suggests biologics may lead to better outcomes for some psoriasis patients. Valeant Pharmaceutical’s brodalumab (Siliq) is reportedly the first product to demonstrate 100 percent improvement in the psoriasis area and severity index (PASI 100) as a primary endpoint in clinical trial Furthermore, biologics have the potential to improve patient quality of life beyond the actual treatment paradigm, including lower levels of anxiety, social dysfunction, sleep disturbance and somatic symptoms.
However, the cost of biologics is rising, and they are typically more expensive than oral systemic therapies. Yet there is some positive news: A study published in the British Journal of Dermatology found biologics that treat moderate to severe plaque psoriasis reduces costs associated with major changes in the pattern of healthcare delivery, reduces the number of inpatient admissions by more than half and reduces the mean number of inpatient days by more than 75 percent. This suggests the higher cost of biologics may be offset by reductions in hospital stays-typically for infectious disease-and improved patient outcomes.
Compared to small-molecule systemic therapies, biologics are usually associated with fewer adverse events because they tend to focus on specific processes and do not have sweeping effects throughout the whole body.
Adverse events can be experienced, however, and those that do occur can be severe, as exemplified by two FDA-approved treatments for plaque psoriasis. Merck’s efalizumab (Raptiva), prior to withdrawal from the US market in 2009, had a boxed warning that highlighted the risk of bacterial sepsis, viral meningitis, invasive fungal disease, progressive multifocal leukoencephalopathy (PML), and other infections. Additionally, Valeant’s brodalumab has a boxed warning for increased risk of suicidal behavior and is only available through a restricted program.
Due to these rare but potentially serious side effects, patient safety is a major consideration in biologics trials compared to studies of other dermatologic agents. Now, the level of oversight is greater, safety monitoring is more frequent, and safety teams, usually small for dermatology studies, have become much larger. In clinical trials, detailed inclusion/exclusion criteria are strictly enforced to protect patients.
While further research is needed, dermatology patients and physicians still welcome the overall benefits and safety profiles of biologic treatments. Patients are experiencing greater skin clearance and quality of life than ever before. As pharma continues to navigate compliance, cost, and safety with care, it is fair to expect the sector to advance and grow for many years to come.
For more information, visit NovellaClinical.com/dermatology
Darcee Strube is Senior Vice President, Dermatology Division, Novella Clinical.