Biological therapies have revolutionized treatment of many autoimmune diseases spanning the therapeutic areas of rheumatology, dermatology, and gastroenterology. In dermatology, despite a need for efficacious therapies in many indications including psoriasis, atopic dermatitis, and scleroderma, drug developers have mainly focused their efforts on the lucrative psoriasis market. In the past decade, the psoriasis market has seen approval of numerous biologics offering greater efficacy in achieving skin clearance and improving patients’ quality of life than topical agents and conventional systemic therapies. In 2015, biologics sales accounted for 80% of the total psoriasis sales in the combined market of the United States and the EU5 countries (France, Germany, Italy, Spain, and the United Kingdom)1.
The multibillion-dollar psoriasis biologics market is dominated by the leading TNF-alpha inhibitors, Amgen/Pfizer’s Enbrel and AbbVie’s Humira, and by Janssen’s IL-12/23 inhibitor Stelara—agents representing the first wave of psoriasis biologics (approved between 2004 and 2009). However, a major hurdle to accessing biological therapies is the cost of treatment. This dictates that they are typically reserved for patients who are contraindicated to or inadequately respond to comparatively low-cost topical or conventional systemic agents. In the United States, for the top three biologics in psoriasis, the cost of one-year induction and maintenance treatment in 2014 was highest for Stelara ($53,339), followed by Enbrel ($46,395) then Humira ($39,041)2. With the burgeoning use of biologics in psoriasis and the entry of a new wave of biological agents led by the IL-17 inhibitors, the burden of healthcare costs is growing, and gaining optimal pricing and reimbursement (P&R) and favorable formulary positioning is increasingly difficult in the cost-constrained EU5 countries as well as in the United States, which is becoming more and more sensitive to high drug prices.
Atopic dermatitis, on the other hand, is traditionally a low-cost, highly genericized market. The mainstays of therapy are topical corticosteroids and topical calcineurin inhibitors. Patients who cannot be controlled with topical treatments can be treated with systemic immunomodulators such as cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil. In the United States, all the systemic immunomodulators are used off-label for atopic dermatitis, whereas in Europe, cyclosporine is approved for the indication. Since the mainstream treatments are inexpensive, payers in the major markets have not had much motivation to implement prescribing restrictions in this market. But this serene state of affairs is doomed to change with the imminent market penetration of premium-priced biologics. The first biological treatment for atopic dermatitis, Sanofi/Regeneron’s IL-4/13 inhibitor Dupixent, has already launched in the United States, and is expected to receive approval in Europe in 2018. In the next few years, the biologics space will potentially pullulate with the expected approvals of AstraZeneca/Leo Pharma’s IL-13 inhibitor tralokinumab, Roche’s IL-13 inhibitor lebrikizumab, and Chugai/Galderma’s IL-31 inhibitor nemolizumab in many major markets. Atopic dermatitis drug developers would be prudent, therefore, to learn from the market access challenges faced by the more established psoriasis biologics market, particularly in EU5 where typically emphasis is placed on not only a drug’s improvement over current standard of care, but also its impact on national, regional, and local healthcare budgets.
In the United States, according to the Institute for Clinical and Economic Review (ICER), the top three psoriasis biologics are cost effective. The costs per additional QALY (Quality-adjusted life-year) for these three biologics are: Stelara: $129,904 per QALY; Humira: $108,040 per QALY; and Enbrel: $117,769 per QALY, all of which are below payers’ willingness-to-pay threshold of $150,000 per QALY3. For the atopic dermatitis biologic Dupixent, the ICER’s draft guidance using an estimated price of $30,000 for one year of treatment has projected Dupixent to be cost-effective in patients with moderate to severe atopic dermatitis, with an estimated cost per additional QALY of $97,600; therefore, also below the commonly-cited willingness-to-pay threshold4. The actual list price of Dupixent, $37,000 per year, falls close to the ICER’s estimated price of $30,000 per year. Based on the list price, many market analysts hail that Dupixent is priced responsibly considering the company could have pursued a higher price point similar to that of the latest biologics in the psoriasis market. Express Scripts has included Dupixent on its National Preferred Formulary, and have praised the company for engaging with them early to ensure access to relevant patients5. With positive payer sentiments, Dupixent would likely be readily available to patients and may not be subject to such exhaustive step therapy and prior authorization requirements as those for some of the later psoriasis biologics that typically limit access to innovative treatments.
In the EU5, obtaining European marketing authorization is just the first step in the long process of achieving market access. Health technology assessments (HTA) and P&R negotiations represent key additional challenges. Successful navigation of the market access and reimbursement environment at multiple levels—national, regional, and local—is crucial for a drug’s success. Demonstration of robust efficacy is a requisite for novel psoriasis agents, with increasing importance placed on careful clinical trial design with appropriate active comparators, specifically the standard of care biologics Humira, Enbrel, or Stelara; placebo-controlled studies are no longer sufficient for securing optimal market access in this competitive space. Additionally, in all EU5 countries, but especially in the United Kingdom, demonstration of cost-effectiveness continues to be essential for national-level HTAs. For example, Celgene’s Otezla, an oral PDE4-inhibitor, which only boasts moderate efficacy in psoriasis, has faced notable challenges in gaining favorable market access across the EU5. After receiving EU approval for psoriasis in January 2015, the United Kingdom’s National Institute for Health and Care Excellence (NICE) initially rejected Otezla because it was too expensive to pass the threshold for cost-effectiveness. Only after resubmission with a patient access scheme (PAS) lowering the cost of the drug, did Otezla receive a positive recommendation from NICE, in November 2016, facilitating National Health Service (NHS) funding6.
In the cost-conscious EU5 market, Dupixent manufacturers may consider applying some of the strategies that the psoriasis biologics manufacturers have found successful. Dupixent has already proven its effectiveness in underserved moderate to severe atopic dermatitis patients, and meeting this unmet need paves the way for favorable HTA in countries such as Germany, France and Italy that score on improvement over existing therapies in the disease area and, in Italy especially on innovation. Use of an appropriate active comparator in clinical trials has become a standard approach in psoriasis trials for emerging biologics and an important requirement for favorable HTA recommendations. While this is not yet standard practice in atopic dermatitis, developers of the upcoming biologics for this indication should start thinking about appropriate comparators and use them to differentiate themselves from the competition.
In Germany, Novartis’s psoriasis biologic Cosentyx was found to offer no added first-line benefit over existing biologics, with the lack of direct comparative studies highlighted alongside the inadequate duration of indirect comparisons. However, within the moderate to severe psoriasis population refractory to conventional systemic agents, an additional benefit was determined and significant added benefit in those previously treated with biologics6. Thus for Dupixent, focusing on an underserved subpopulation, the moderate to severe refractory atopic dermatitis patients, and proving cost effectiveness in this subpopulation could be a fruitful strategy7. Already in the United Kingdom, the Early Access to Medicines Scheme (EAMS), recognizing the burden of severe atopic dermatitis, has granted early access to Dupixent, prior to EMA marketing authorization of the drug 8.
Market access challenges represent significant barriers to optimal uptake of premium-priced biologics. If not addressed strategically, these can lead to the drug being relegated to later-lines of treatment with limited patient share. Therefore, considerable attention must be paid to identifying levers including a demonstration of cost-effectiveness in overall patient care, targeting a highly underserved patient population, improving the standard of care, and responsible pricing, with consideration of managed entry schemes in the EU5. Such strategies can provide a unique competitive advantage for the innovator drug and result in favorable P&R negotiations in Europe and formulary positioning in the United States.
- 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
- Feldman, S. R., The cost of biologics for psoriasis is increasing. Drugs context. 2014, 3:212266.
- Hefferman, M. P., Rising costs of biologics: are patients getting enough “bang for the bucks”? Controversies and difficult questions concerning biologic therapeutics session. American Academy of Dermatology Annual Meeting; 2017, Orlando, S046.
- ICER, Dupilumab and Crisaborole for atopic dermatitis: effectiveness and value, Draft Evidence Report, March 24, 2017.
- The Center for Biosimilars, Strong Early Launch for New Eczema Drug Dupilumab, Despite Price, press release, May 11, 2017.
- Secukinumab in psoriasis: now indication of added benefit for certain patients. IQWIG, press release, November 11, 2015.
- For further detailed analyses on the atopic dermatitis, access and reimbursement (EU5) based on primary research please see: DRG’s Atopic Dermatitis, Access and Reimbursement, EU5
- UK patients granted early access to Sanofi’s innovative dermatology treatment dupilumab by MHRA. Sanofi, press release, March 14, 2017.