With the High Efficacy Bar That TNF-Alpha Inhibitors Set, What Are the Remaining Areas of Opportunities for Emerging Therapies to Fill?

Nine biologics are approved to treat rheumatoid arthritis (RA), along with an oral kinase inhibitor (tofacitinib [Pfizer/Takeda’s Xeljanz]). Given rheumatologists’ long-standing familiarity with the safety and efficacy profiles of the TNF-α inhibitors, the first of which was approved in 1998, and, increasingly, of abatacept (Bristol-Myers Squibb/Ono Pharmaceutical’s Orencia), rituximab (Biogen Idec/Roche/Chugai/Zenyaku Kogyo’s Rituxan, Roche’s MabThera), and tocilizumab (Roche/Chugai’s RoActemra/Actemra), new agents face challenges in gaining uptake. To help drug developers negotiate the formidable barriers to uptake in this market, this report identifies attributes with the greatest power to sway rheumatologists’ prescribing decisions and the gaps in efficacy and safety of select current and emerging therapies.

Questions Answered in This Report:

  • A drug’s performance on the signs and symptoms of RA, improving physical function, inducing clinical remission, and inhibiting structural damage are efficacy measures that are very important to rheumatologists. 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 each efficacy measure in their prescribing decision for RA?

  • Therapies with greater ability to halt structural damage progression and induce clinical remission are key areas of unmet need in RA, according to surveyed U.S. and European rheumatologists. Which therapies in development for RA 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?

  • A drug’s effect on the signs and symptoms of RA and risk of serious infection are key drivers of physicians’ prescribing decisions for new RA therapies. What trade-offs across these and other clinical attributes (including formulation) are U.S. rheumatologists willing to make when considering the use of emerging therapies for RA? 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 RA?

  • Based on its clinical profile, abatacept is the clinical gold standard in our Drug Comparator Model. What attributes do thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge abatacept as the future gold standard in 2017 or 2022?


Attributes included in conjoint analysis based assessment of target product profiles for RA:

- % of methotrexate-refractory patients achieving an ACR 20 response at six months (adjusted to placebo + methotrexate).

- % of methotrexate-refractory patients achieving an ACR 50 response at six months (adjusted to placebo + methotrexate).

- Mean change (from baseline) in modified TSS score in methotrexate-refractory patients at one year.

- % of methotrexate-refractory patients achieving clinical remission (DAS28 < 2.6)="" at="" six="">

- Rate of serious infections per 100 patient-years (placebo-adjusted).

- Drug formulation.

- Price.

Attributes included in assessment of U.S. payers’ receptivity to new therapies for RA:

- Effect on signs and symptoms of RA (ACR 50 response rate) in methotrexate-refractory patients at six months.

- Effect on progression of structural damage (modified Total Sharp Score [mTSS]) in methotrexate-refractory patients at one year.

- Effect on remission (DAS28 < 2.6)="" in="" methotrexate-refractory="" patients="" at="" six="">

- Associated risk of serious infections (per 100 patient-years).

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:

Current Therapies

- Etanercept (Amgen/Pfizer/Takeda’s Enbrel)

- Tofacitinib (Pfizer/Takeda’s Xeljanz)

- Tocilizumab (Roche/Chugai’s Actemra/RoActemra)

- Abatacept (Bristol-Myers Squibb/Ono Pharmaceutical’s Orencia)

- Rituximab (Biogen Idec/Roche/Chugai/Zenyaku Kogyo’s Rituxan, Roche’s MabThera

Emerging Therapies

- Baricitinib (Eli Lilly/Incyte)

- Sirukumab (Janssen/GlaxoSmithKline)

- Sarilumab (Sanofi/Regeneron)

- Secukinumab (Novartis)

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