DecisionBase

April 2013

Depression (Treatment-Resistant)

Introduction:

In the Crowded Antidepressant Market Space, What Are the Remaining Opportunities for New Therapies for TRD?

Unipolar depression, which includes major depressive disorder (MDD), minor depression, and dysthymia, is a highly prevalent psychiatric disorder—we estimate 87 million prevalent cases in the seven major pharmaceutical markets by 2021. Treatment-resistant depression (TRD), a subset of MDD, is frequently defined as an inadequate response to two trials of major antidepressants from two different classes. Atypical antipsychotics—e.g., Abilify (Bristol-Myers Squibb/Otsuka Pharmaceutical’s aripiprazole), a therapy approved for patients who do not respond adequately to antidepressant therapy—are increasingly used to augment antidepressants in TRD treatment. The unipolar depression market, including therapies approved for TRD, is a mature market with few remaining branded agents. Nevertheless, opportunity remains for emerging drugs that can provide efficacy in TRD that is comparable to that of antipsychotic augmentation.

Questions Answered in This Report:

  *   The percentage of TRD patients who respond to treatment, the percentage of TRD patients who experience remission of depressive symptoms, and the reduction of depressive symptoms are key goals in the treatment of treatment-resistant depression. What are the key primary and secondary clinical trial end points by which new therapies are evaluated? How do U.S. and European psychiatrists weight specific efficacy end points and other drug attributes in their prescribing decisions for TRD?

  *   Higher remission rates and greater long-term efficacy on depressive symptoms are key areas of unmet need for treatment-resistant depression, according to surveyed U.S. and European psychiatrists. Which therapies in development for TRD are poised to fulfill these needs? What clinical and/or regulatory challenges must drug developers overcome 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 indicated there is high unmet need?

  *   Risk of significant weight gain and effect on depressive symptoms at six weeks are key drivers of physicians’ prescribing decisions for TRD and/or are the focus of new drug development for TRD. What trade-offs across these and other clinical attributes are U.S. psychiatrists willing to make when considering the use of emerging therapies for the treatment of TRD? Given the trade-offs in price and performance across key drug attributes that U.S. psychiatrists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for TRD?

  *   By 2016, Eli Lilly’s edivoxetine will emerge as the gold-standard therapy in our Drug Comparator Model because its clinical profile is superior to that of the key current TRD therapies we evaluated. On what clinical attributes is edivoxetine, as an adjunctive TRD therapy, most differentiated from its competitors? Which current TRD therapies are at greatest risk of being replaced by edivoxetine?

Scope:

Attributes included in conjoint analysis-based assessment of target product profiles for treatment-resistant depression:

- Effect on depressive symptoms at six weeks as adjunct to antidepressant therapy

- Long-term efficacy as adjunct to antidepressant therapy

- Risk of fatigue as adjunct to antidepressant therapy

- Risk of sexual dysfunction as adjunct to antidepressant therapy

- Risk of significant weight gain as adjunct to antidepressant therapy

- Dosing frequency

- Price per day

Attributes included in assessment of U.S. payers’ receptivity to new therapies for treatment-resistant depression:

- Effect on depressive symptoms in TRD patients

- Risk of weight gain

- Risk of sexual dysfunction

Physicians surveyed: 60 U.S. and 30 European psychiatrists

Payers surveyed: 20 U.S. MCO PDs

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Aripiprazole (Bristol-Myers Squibb/Otsuka Pharmaceutical’s Abilify) + antidepressant

- Quetiapine XR (AstraZeneca’s Seroquel XR/Seroquel XL/Seroquel Prolong/Xeroquel LP, generics) + antidepressant

- Olanzapine/Fluoxetine Combination (OFC; Eli Lilly’s Symbyax, generics)

- Bupropion SR + citalopram (GlaxoSmithKline’s Wellbutrin SR, generics + Forest Laboratories Celexa, generics; Lundbeck’s Cipramil, generics)

- Venlafaxine XR + Mirtazapine (Pfizer’s Effexor XR, generics + Merck & Co.’s Remeron/Remergil/Norset/Rexer/Zispin, generics)

Emerging Therapies

- Edivoxetine (Eli Lilly) + antidepressant

- Vortioxetine (Lundbeck/Takeda Pharmaceuticals’ Brintellix)

- Levomilnacipran (Forest Laboratories/Pierre Fabre)

- Brexpiprazole (Lundbeck/Otsuka) + antidepressant

- Lurasidone (Dainippon Sumitomo Pharma/Sunovion/Takeda’s Latuda)


Search Reports

Mentioned in this report:

  • - AstraZeneca
  • - Bristol-Myers Squibb
  • - Dainippon Sumitomo Pharma
  • - Eli Lilly
  • - Forest Laboratories
  • - GlaxoSmithKline
  • - Janssen
  • - Lundbeck
  • - Merck & Co.
  • - Mitsubishi Tanabe Pharma
  • - Mochida Pharmaceuticals
  • - Organon
  • - Otsuka Pharmaceuticals
  • - Pfizer
  • - Pierre Fabre
  • - Servier
  • - Shionogi & Co.
  • - Sunovion
  • - Takeda Pharmaceuticals
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