Introduction:Opportunity Awaits Therapies Offering Improvements in Efficacy and Safety over Currently Available TNF-Alpha Inhibitors
The availability of tumor necrosis factor alpha (TNF-α) inhibitors as therapeutic options has revolutionized the treatment of psoriatic arthritis (PsA). The TNF-α inhibitors have set a high clinical standard (e.g., excellent efficacy in both peripheral and axial PsA, low risk of organ toxicity) that is challenging for emerging therapies to surpass. However, unmet needs exist for improvements in various efficacy, safety and tolerability, and delivery attributes. A number of therapies, including those that will offer improvements over the TNF-α inhibitors on delivery or safety, are in late-stage development for PsA; however, based on the current trial data for these agents, significant opportunity remains for new drugs that offer efficacy that surpasses that of the TNF-α inhibitors.
Questions Answered in This Report:
Reduction of signs and symptoms of peripheral disease, inhibition of structural damage progression, and psoriatic plaque clearance are key goals in the treatment of PsA. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European rheumatologists weight specific efficacy end points and other drug attributes in their prescribing decisions for PsA?
Therapies offering a greater reduction in the signs and symptoms of axial disease, a greater ability to halt progression of structural damage, and a lower risk of serious infections represent key areas of unmet need for PsA according to the insights of surveyed U.S. and European rheumatologists. Which therapies in development for PsA are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome in order to capitalize on these areas of unmet need? What degree of improvement over currently available therapies do surveyed U.S. MCO PDs seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?
Effect on peripheral disease and effect on skin are key drivers of physicians’ prescribing decisions and are the focus of drug development for new PsA therapies. What trade-offs across these and other clinical attributes are U.S. rheumatologists willing to make when considering the use of emerging therapies for the treatment of PsA? Based on the trade-offs in price and performance across key drug attributes that U.S. rheumatologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for PsA?
Despite the potential launch of several emerging therapies in the PsA market over the next ten years, adalimumab (AbbVie/Eisai’s Humira) and certolizumab pegol (UCB/Astellas Pharma’s Cimzia) will remain the gold-standard therapies in our Drug Comparator Model. On what clinical attributes are adalimumab and certolizumab pegol most differentiated from their competitors? What are the weaknesses of these therapies on which emerging therapies can capitalize? Which emerging therapies, if any, pose the greatest threat to adalimumab and certolizumab pegol as well as the other key current therapies?
Attributes included in conjoint analysis based assessment of target product profiles for PsA:
- Effect on peripheral disease—ACR 20 response at 6 months (% of patients, placebo-adjusted).
- Effect on axial disease—ASAS 20 response at 6 months (% of patients, placebo-adjusted).
- Effect on skin—PASI 75 response at 6 months (% of patients, placebo-adjusted).
- Risk of liver toxicity (% of patients with alanine transaminase [ALT] levels >3x the upper level of normal [ULN], placebo-adjusted).
- Rate of serious infections (per 100 patient-years, placebo-adjusted).
- Delivery burden (drug formulation and dosing).
Attributes included in assessment of U.S. payers’ receptivity to new therapies for PsA:
- Effect on signs and symptoms of arthritis (ACR 20 response at 6 months).
- Effect on skin (PASI 75 response at 6 months).
- Rate of serious infections (per 100 patient-years).
- Formulation and dosing frequency.
Physicians surveyed: 60 U.S. and 30 European rheumatologists.
Payers surveyed: 20 U.S. MCO PDs.
Comprehensive List of Therapies Included in Our Research and Modeling:
- Etanercept (Amgen/Pfizer/Takeda Pharmaceutical’s Enbrel)
- Adalimumab (AbbVie/Eisai’s Humira)
- Infliximab (Janssen Biotech/Merck/Mitsubishi Tanabe Pharma’s Remicade)
- Ustekinumab (Janssen Biotech’s Stelara)
- Certolizumab pegol (UCB/Astellas Pharma’s Cimzia)
- Methotrexate (Dava Pharmaceuticals’ Rheumatrex, generics)
- Apremilast (Celgene’s Otezla)
- Tofacitinib (Pfizer/Takeda Pharmaceutical’s Xeljanz)
- Secukinumab (Novartis)
- Abatacept (Bristol-Myers Squibb/Ono Pharmaceutical’s Orencia)