In an Increasingly Generic Market, Replete with Well-Established Oral Therapies, What Drug Development Opportunities Remain?

In 2012, painful diabetic neuropathy (PDN) affected more than 7.4 million people in the major pharmaceutical markets under study (United States, France, Germany, Italy, Spain, United Kingdom, and Japan); due to an aging population and increases in obesity and type 2 diabetes, this market is expected to grow to more than 9.5 million by 2022. In addition to offering a rather large treatable patient population, PDN has and will continue to serve as a gateway indication into the broader, more-lucrative neuropathic pain (NP) market. No available therapies for PDN, and NP in general, can fully alleviate patients’ pain; interviewed experts report that, despite the availability of a large array of therapies from multiple drug classes, physicians are at best able to achieve 50% pain relief in 50% of their PDN patients with any single therapy. The limited efficacy and tolerability of currently available therapies translate into a high level of unmet need and potential opportunity for novel agents. However, emerging pain therapies will enter a market that contains many well-established, relatively inexpensive early-line therapies and will encounter a growing generics presence. As a result, emerging therapies attempting to attain premium pricing in this market will need to offer substantial improvements in efficacy, safety, and/or delivery over currently available therapies to achieve commercial success.

Questions Answered in This Report:

  • A drug’s performance on at least eight efficacy end points, including patient responder rate (as measured by the percentage of patients with ≥ 30% or ≥ 50% reduction from baseline in pain intensity), is important for drug approval and physician use. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European neurologists weight efficacy measures and other drug attributes in their prescribing decisions for PDN?

  • Pregabalin (Pfizer’s Lyrica) is the 2012 major-market sales leader for PDN. What weaknesses exist in its profile that would allow emerging therapies to gain a foothold in the market? Have emerging therapies demonstrated strengths on the attributes that surveyed neurologists indicate are the most important in their prescribing decisions? Which emerging therapies will offer the clinical improvements over currently available therapies that surveyed MCO PDs seek from new therapies?

  • Reduction in pain intensity and patient responder rate are key drivers of physicians’ prescribing decisions for new PDN therapies. What trade-offs across these and other clinical attributes are U.S. neurologists willing to make when considering the use of emerging therapies for the treatment of PDN? Based on the trade-offs in price and performance across key drug attributes that U.S. neurologists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for PDN?

  • By 2017, Acorda Therapeutics’ capsaicin topical solution (NP-1998) will emerge as the gold-standard therapy in our Drug Comparator Model because of its superior clinical profile over that of the key current therapies we evaluated. On what clinical attributes is capsaicin topical solution most differentiated from its competitors? Which current therapies are at greatest risk of being replaced by capsaicin topical solution, and to what extent do surveyed U.S. neurologists anticipate prescribing the agent in combination with available therapies?


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

- Reduction in 11-point pain intensity score.

- Percentage of patients achieving ≥ 50% reduction in pain intensity score.

- Percentage of patients reporting “much improved” or “very much improved” on the Patient Global Impression of Change (PGIC) scale.

- Incidence of weight gain; percentage of patients reporting a gain of 7% or more over baseline.

- Dosing frequency.

- Dosage formulation.

- Price/day.

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

- Patient responder rate (percentage of patients achieving a ≥ 50% reduction in pain).

- Effect on global outcomes (percentage of patients reporting “much improved” or “very much improved” on the PGIC scale).

- Delivery characteristics.

- Average weight change (pounds [lbs] lost or gained).

Physicians surveyed: 62 U.S. and 30 European neurologists.

Payers surveyed: 20 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Pregabalin (Pfizer’s Lyrica)

- Gabapentin (Pfizer’s Neurontin, generics)

- Duloxetine (Eli Lilly/Shionogi’s Cymbalta/Xeristar, generics)

- 5% lidocaine patch (Endo’s Lidoderm, Grünenthal’s Versatis, generics)

- Tapentadol ER (Janssen’s Nucynta ER, Grünenthal’s Palexia SR)

Emerging Therapies

- Pregabalin CR (Pfizer)

- Capsaicin topical solution (Acorda Therapeutics’ NP-1998)

- Clonidine topical gel (BioDelivery Sciences)

- XEN-402 (topical) (Teva/Xenon)

- Eslicarbazepine acetate (Bial)