Biologics continue to flare up the psoriasis market, indicating opportunities in the larger dermatology space

Psoriasis is a common chronic skin disorder affecting approximately 9.3 million Americans. It is also associated with several comorbidities such as obesity, hypertension, psoriatic arthritis, depression, and diabetes. Psoriasis is characterized by skin flares and inflammation that vary in severity, from minor localized patches to substantial body surface involvement. Around 20% of diagnosed patients have moderate to severe psoriasis. Currently, in the United States, psoriasis is a $5 B market, of which 90% are from drugs targeting moderate to severe psoriasis patients where the skin manifestation affects more than 3% of the body. For such patients, psoriasis is often a debilitating condition impacting their quality of life and psychological well-being. Over the past decade, biologics have altered the landscape in the management of moderate to severe psoriasis by achieving improved skin clearance, control of symptoms and quality of life for hundreds of thousands of individuals affected.

Before the advent of biologics, in 2003, psoriasis was merely a $700 M market in the United States, dominated by systemic therapies such as methotrexate, cyclosporine, and acitretin, which were used when topical therapy was too expensive for extensive psoriasis or when patients were refractory to topical therapy and phototherapy. While these medications are moderately effective, they suppress the entire immune system, requiring clinicians to do routine laboratory monitoring because of increased liver and renal toxicity, hematologic side effects, and myelosuppression. Systemic therapies are also contraindicated in various patient subpopulations, such as pregnant women, nursing mothers and individuals with liver or kidney disease. Thus a huge unmet need existed for therapies that were safe for long-term use, offered efficacy in moderate to severe psoriasis patients, and provided an alternative to patients who were refractory or contraindicated to conventional systemics.

Psoriasis is linked to pathogenesis caused by dysregulation of T-cell-dependent immune response, as well as hyperproliferation of keratinocytes, the predominant cell type on the outer layer of skin. Biologics target the cytokines usually upregulated as a result of the abnormal immune response. Currently, there are six FDA-approved biologics for the treatment of psoriasis belonging to three separate drug classes: TNF-α inhibitors including Humira (adalimumab, AbbVie), Enbrel (etanercept, Amgen), and Remicade (infliximab, Janssen Biotech), the IL-12/23 inhibitor Stelara (ustekinumab, Janssen Biotech), and the IL-17 inhibitors Cosentyx (secukinumab, Novartis) and Taltz (ixekizumab, Elli Lilly). Two biologics, Amevive (alefacept, Astellas Pharma) and Raptiva (efalizumab, Merck Serono), initially approved for psoriasis in 2003 were withdrawn from the market in 2011 and 2009 respectively due to insufficient response in patients on Amevive and safety concerns with Raptiva.

TNF-α inhibitors were the first class of biologics that succeeded in delivering clinical improvements to moderate to severe psoriasis patients while still having manageable safety profiles. Enbrel was the first TNF-α inhibitor to be approved (2004), followed by Remicade (2006) and Humira (2008). Within a span of five years before the next biologic with a new mode of action became available in the United States, the psoriasis market skyrocketed from $700 M (2003) to $2 B (2009). In 2009, biologics accounted for 70% of total sales in psoriasis. This was primarily driven by these agents’ potent efficacy, and increasing physician familiarity and comfort with the use of biologics, which elevated the overall biologic treatment rate. Among the TNF-α inhibitors approved for psoriasis, Remicade is the most effective as measured by PASI 75 response rates at 3 months, while Enbrel is slightly weaker than the rest of the agents in this class. Although Humira was the third TNF-α inhibitor approved for psoriasis in the United States, it quickly gained market share on the strengths of its positive clinical profile, subcutaneous formulation compared with intravenous formulation for Remicade, and more-convenient dosing schedule compared with Enbrel (every other week instead of once or twice weekly). On the safety side, Enbrel is generally considered the safest TNF-α inhibitor, which has helped maintain its preferred first-line biologic position among some dermatologists.

While TNF-α inhibitors offered better treatment outcomes, unmet need still existed because many patients did not respond or lost response over time with TNF-α inhibitors. Stelara, the next generation of biologic, approved in 2009, targets cytokines IL 12/23, which are directly involved in psoriasis pathogenesis. While Stelara’s efficacy is similar to Humira, it has an even more convenient dosing schedule (once every three months). The steady growth in the uptake of Stelara is likely owing to patient and physician preference for the more convenient dosing of Stelara over the TNF-α inhibitors. Since the availability of Stelara in 2009, the total U.S. psoriasis market grew by $3 B during 2009-2014, and Stelara alone earned U.S. sales of $1.3 B in 2014. Stelara’s alternative mechanism of action has contributed to a higher biologics-treated rate, as patients who are contraindicated or intolerant to TNF-α inhibitors, as well as patients who have failed multiple TNF-α inhibitors can now be treated with Stelara. The agent’s premium price over TNF-α inhibitors has also contributed to the growth of the market during 2009-2014, with more and more patients receiving Stelara instead of a TNF-α inhibitor as a first- or second-line biologic.

The latest wave of biologics is the IL-17 inhibitors with the first-in-class, Cosentyx (secukinumab, Novartis) launching in 2015 followed by Taltz (ixekizumab, Eli Lilly) in early 2016. These drugs specifically target IL-17, a cytokine involved directly in skin inflammation. IL-17 inhibitors are highly efficacious and offer clinical improvements on stringent end points such as PASI 90 and PASI 100 (total skin clearance) over previous therapies. Initially these drugs will be reserved for patients who fail TNF-α inhibitors and/or Stelara. A small proportion of biologic-naïve patients may receive IL-17 inhibitors because they are intolerant/contraindicated to other biologic drug classes, but the overall biologics treated rate will largely remain steady since these newer drugs will generally replace existing biologics in the market. According to an interviewed French dermatologist, “Patient’s expectations are recalibrated with efficacy improvements. Ten years ago patients were happy with methotrexate and then with anti-TNF-α therapy but now with new drugs they expect further improvements in end results.” Since these new drugs offer efficacy improvements, they also charge premium price, which will be a major driver for growth in sales in the psoriasis market in the next few years.  We expect that the psoriasis market will grow from $5 B in 2014 to $9 B in 2024. The biologics market will become increasingly crowded in the next 10 years, with the entry of yet another new class of biologics, IL-23 targeting drugs; Merck & Co’s tildrakizumab, the first-in-class, is expected to launch in 2017. Thus, the psoriasis biologics market will become more competitive with many drug classes competing for the same moderate to severe patient population.

According to U.S. dermatologists surveyed by DRG, several dermatological conditions that were traditionally not primary targets for drug developers, including atopic dermatitis, hidradenitis suppurativa, and chronic urticarial, have a higher unmet need than moderate to severe psoriasis. Immune and inflammatory pathways play a key role in these dermatological conditions, and several biologics initially developed to treat autoimmune diseases such as psoriasis, rheumatoid arthritis, and allergic asthma have proven effective in some of these dermatological diseases. Recently, Humira was approved for moderate to severe form of hidradenitis suppurativa. Likewise, chronic idiopathic urticaria, a form of chronic urticaria caused by an autoimmune reaction, saw the approval of Xolair, a biologic that reduces an IgE-sensitized allergic immune response in asthma. Atopic dermatitis, a common skin condition, currently has an underserved severe patient population, which is similar to the unmet need that existed in psoriasis before the entry of biologics. Given the similarities such as underserved subpopulations and lack of efficacious long-term therapies between the psoriasis market over a decade ago and the atopic dermatitis market now, continued success of biologics in psoriasis may imply untapped opportunities and huge commercial potential for biologics in atopic dermatitis (see DRG blog post on “launch of targeted therapies will revolutionize the atopic dermatitis treatment”). Drug developers have awakened to this knowledge and a number of biologics are in development, with Regeneron/Sanofi’s IL-4 inhibitor, dupilumab, likely becoming available as early as 2017.

Dupilumab will have a significant first-to-market advantage since the next wave of biologics for atopic dermatitis, IL-13 inhibitors, AstraZeneca/LEO Pharma’s tralokinumab and Roche’s lebrikizumab are not expected to make launches before 2020. In psoriasis, the first biologics, TNF-α inhibitors as a drug class revolutionized treatment of the disease, and subsequent biologics drug classes, IL12/23 and IL-17s have contributed to incremental growth of market size. Given the demonstrated efficacy and safety profile of dupilumab as well as physician enthusiasm towards the agent, we can assume that the drug will experience rapid uptake and exponentially expand the dollar value of the atopic dermatitis market before launch of subsequent biologics. Clinical data for tralokinumab and lebrikizumab are limited, therefore it is too early to predict the extent of impact of these IL-13 inhibitors on the atopic dermatitis market. Since these two agents target the same patient population as dupilumab in clinical trials, if approved, they will likely be used primarily in patients who have failed or are contraindicated to dupilumab, thus will contribute to incremental growth of the market, like what Stelara and the IL-17 inhibitors have contributed to the psoriasis market. Overall, since the entry of biologics in psoriasis, the market has grown manifolds and has seen many waves of biologics that till date continue to fuel its growth. The future competitive landscape and potential size of the atopic dermatitis biologics market have to be determined by multiple factors, among which the efficacy and safety profile of each biologic in pivotal clinical trials, exact time of launch, pricing and reimbursement negotiations with payers, and physician and patient engagement will all play important roles.

 

Sources:

  1. For further detailed analyses on the Psoriasis market based on primary research with key opinion leaders please see: DRG’s Psoriasis Disease Landscape and Forecast
  2.  For further detailed analyses on the Unmet Needs in the Psoriasis market based on primary research please see: DRG’s Psoriasis Unmet Need
  3. For further detailed analyses on the Atopic Dermatitis market based on primary research with key opinion leaders please see: DRG’s Atopic Dermatitis Landscape and Forecast  

 

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