By: Vania Galarraga, MPH, Engagement ManagerSkin diseases constitute one of the leading causes of health burden worldwide, measured as disability-adjusted life years (DALYs). Among skin diseases, psoriasis (PsO) carries the third-largest disability weight, which translates into health loss and poor quality of life (QoL)1. Globally, approximately 1-8% of the population suffers from PsO2, 3. Among PsO patients, the prevalence of psoriatic arthritis (PsA) is estimated to be between 6% and 41%3.
Anti-TNFs have historically been the biologic of choice to treat PsO and PsA; however, they were not prescribed in many instances, even if the patient was eligible, due to safety concerns. For some time now, several companies have been challenging the anti-TNFs’ leadership in this space. Newer agents have shown improved efficacy in comparison to the anti-TNFs and provide complete or near-complete skin clearance to patients with even severe disease. As newer agents enter the market, patient segmentation will become ever more complex, with multiple options available to treat each indication and several mechanisms of action from which to choose.
To succeed in the PsO and PsA market, biopharmaceutical companies should consider the following questions:
How Are Newer Biologics Changing the Market Dynamics?
- PASI 90 and PASI 100 have become increasingly relevant by showing that patients who achieved PASI 90 with newer agents could have better QoL than those who achieved PASI 754
- Several head-to-head trials now aim to measure PASI 90 (at Weeks 16 and 52) as the primary outcome; this is a shift from the historical trend of measuring PASI 75 as the primary endpoint5, 6, 7
- Companies are using the social stigma around PsO lesions to emphasize that the treatment goal should be complete or near-complete skin clearance
- Recent clinical trial trends indicate that several companies are seeking label extensions in subsets of the PsO patient population, such as those with scalp8 or genital9 involvement
- Anti-IL-23s offer a more convenient dosing regimen (e.g., Q12W10 or Q16W in super-responders11) when compared to anti-TNFs. Head-to-head superiority data of anti-IL-17s and anti-IL-23s against anti-TNFs have been positively received
- Although dermatologists have historically expressed concerns regarding the potential safety implications associated with targeted inhibition of cytokine pathways, a recent publication in JAMA Dermatology12 showed no difference in increased risk of cardiovascular comorbidities between Janssen’s Stelara (ustekinumab) and anti-TNFs
What Roles Do Convenience and Safety Play in the Treatment Paradigm?
- Oral agents such as Celgene’s Otezla (apremilast) provide an attractive option for patients with moderate PsO who might prefer the convenience of an oral therapy before trying an injectable
- In the case of active PsA, the launch of JAK inhibitors, led by Pfizer’s Xeljanz (tofacitinib), has intensified competition. As next-generation JAK inhibitors are approved and their share of voice increases, there could be a considerable treatment paradigm shift that affects prescribing practice and treatment sequencing in PsA and, eventually, PsO. Although there have been some safety concerns around the higher doses, there seems to be growing familiarity and comfort around the safety profile of JAK inhibitors. An effective oral drug with acceptable safety could disrupt the fast-changing marketplace
- Tyk2 inhibitors are also expected to provide an additional oral option. Phase II results of Bristol-Myers Squibb’s BMS-986165 showed the ability of this class to achieve PASI 90 and PASI 10013
What Impact Will Biosimilars Have on the PsO and PsA Market?
- Anti-TNFs are expected to face intense competition from innovator products and anti-TNF biosimilars, particularly in Europe14. In the US, anti-TNF biosimilar competition is not expected to intensify until 2023
- Biosimilars will provide the historically proven safety and efficacy of the anti-TNF class while being more cost-effective, leading to increased access to biologics for patients with severe disease
- As a result of competition, developers of reference anti-TNFs are focused on expanding access to their products by increasing the number of approved indications, enhancing their patient support programs and providing additional discounts
Table 1: Key Considerations for a Successful Drug Launch
Patient Segmentation Will Be Key in the Evolving PsO and PsA Market
Given the breadth of options available to treat PsO and PsA, HCPs are likely to tailor therapy to cater to each patient’s needs. Newer agents (anti-IL-17s and anti-IL-23s) have raised patient and prescriber expectations in PsO due to their ability to achieve complete or near-complete skin clearance. Anti-TNF biosimilars are expected to retain some of their market share, as they are likely to be a more economical option than the novel biologics. JAK inhibitors and other novel oral therapies could lead to a significant shift in the treatment paradigm in a market segment traditionally dominated by injectable biologics. Given the complexity of the market dynamics, understanding the role of patient segmentation is going to be critical for success in the PsO and PsA marketplace.
- Hay RJ, Johns NE, Williams HC. et al. The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions. Journal of Investigative Dermatology. 2014; 134(6):1527–1534.
- Parisi R, Symmons DP, Griffiths CE, et al. Global Epidemiology of Psoriasis: A Systematic Review of Incidence and Prevalence. Journal of Investigative Dermatology. 2013; 133(2):377–385
- Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheumatic Diseases Clinics of North America. 2015; 41(4):545–568.
- Novartis. Novartis new data reinforces superiority of Cosentyx® versus Stelara® in achieving skin clearance for psoriasis patients. Press Release, January 16, 2018. https://www.pharma.us.novartis.com/news/media-releases/novartis-new-data-reinforces-superiority-cosentyxr-versus-stelarar-achieving (accessed June 2019).
- Eli Lilly. New Head-to-Head Data Shows Significantly Higher Response Rates for Lilly’s Taltz® (ixekizumab) Compared to Stelara® (ustekinumab) in Patients with Moderate-to-Severe Plaque Psoriasis. Press Release, March 4, 2017. https://investor.lilly.com/news-releases/news-release-details/new-head-head-data-shows-significantly-higher-response-rates (accessed June 2019).
- US National Library of Medicine. Risankizumab Versus Secukinumab for Subjects With Moderate to Severe Plaque Psoriasis. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03478787?term=Psoriasis+Area+and+Severity+Index+%28PASI%29+90&cond=Psoriasis&rank=7 (accessed May 2019).
- US National Library of Medicine. Study of Secukinumab Compared to Ustekinumab in Subjects With Plaque Psoriasis (CLARITY). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02826603 (accessed May 2019).
- US National Library of Medicine. Efficacy and Safety of Subcutaneous Secukinumab in Adults With Moderate to Severe Scalp Psoriasis (SCALP). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02267135?term=Secukinumab&cond=Scalp+Psoriasis&rank=1; A Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis of the Scalp (STYLE) https://clinicaltrials.gov/ct2/show/NCT03123471?term=apremilast&cond=Scalp+Psoriasis&rank=2 (accessed May 2019).
- US National Library of Medicine. A Study of Ixekizumab (LY2439821) in Participants With Moderate-to-Severe Genital Psoriasis (IXORA-Q). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02718898?term=ixekizumab&cond=genital+psoriasis&rank=1 (accessed May 2019).
- AbbVie. AbbVie Expands Immunology Portfolio in the U.S. with FDA Approval of SKYRIZI™ (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis. Press Release, April 23, 2019. https://news.abbvie.com/news/press-releases/abbvie-expands-immunology-portfolio-in-us-with-fda-approval-skyrizi-risankizumab-rzaa-for-moderate-to-severe-plaque-psoriasis.htm (accessed May 2019).
- US National Library of Medicine. A Study to Evaluate Further Therapeutic Strategies With Guselkumab in Participants With Moderate-to-Severe Plaque-Type Psoriasis (GUIDE). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03818035 (accessed May 2019).
- Lee MP, Desai RJ, Jin Y, et al. Association of Ustekinumab vs TNF Inhibitor Therapy With Risk of Atrial Fibrillation and Cardiovascular Events in Patients With Psoriasis or Psoriatic Arthritis. JAMA Dermatology. 2019; 155(6):700–707.
- Kim P, Kenneth G, Diamant T, et. al. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. New England Journal of Medicine. 2018; 379:1313-1321
- IQVIA. Advancing Biosimilar Sustainability in Europe: A Multi-Stakeholder Assessment. Institute Report. https://www.iqvia.com/institute/reports/advancing-biosimilar-sustainability-in-europe (accessed May 2019).