How Can Emerging Augmentation Strategies Be Differentiated to Maximize Uptake in a Mature and Genericized Market?

Unipolar depression, which includes major depressive disorder (MDD), minor depression, and dysthymia, is a highly prevalent psychiatric disorder; we estimate 87.5 million prevalent cases in the seven major pharmaceutical markets by 2023. Treatment-resistant depression (TRD), a subset of the MDD population, is frequently defined as an inadequate response to two trials of major antidepressants from two different drug classes. Atypical antipsychotics—e.g., aripiprazole (Bristol-Myers Squibb/Otsuka Pharmaceutical’s Abilify), a therapy approved for MDD patients who do not adequately respond 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 a limited number of branded agents. Nevertheless, opportunity exists for emerging drugs that can provide efficacy and/or safety in TRD that is comparable to or better than that of atypical antipsychotic augmentation.

Questions Answered in This Report:

  • The percentage of TRD patients who experience remission of depressive symptoms, the percentage of TRD patients who respond to treatment, and the reduction of depressive symptoms in TRD patients are key goals in the treatment of TRD. What are the key primary and secondary clinical trial end points with 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?

  • Greater remission rates in TRD patients and higher treatment response rates in TRD patients are key areas of unmet need for TRD, according to the insights of surveyed U.S. and European psychiatrists. Which therapies in development for TRD, if any, 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. managed care organization pharmacy directors (MCO PDs) seek from new therapies on key clinical attributes for which surveyed physicians indicate there is high unmet need?

  • Delivery burden, risk of significant weight gain as adjunct to antidepressant therapy, and long-term efficacy as adjunct to antidepressant therapy are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new TRD therapies. 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? Based on 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?

  • Based on its clinical profile, vortioxetine (Lundbeck/Takeda Pharmaceutical’s Brintellix) is the current clinical gold standard in our Drug Comparator Model. What attributes do interviewed thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge vortioxetine as the future gold standard in 2018 or 2023?

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 (MADRS score improvement).

- Long-term efficacy as adjunct to antidepressant therapy: % of patients with improved CGI-S score at 52 weeks.

- Time to onset of therapeutic effect.

- Risk of sexual dysfunction as adjunct to antidepressant therapy: % of TRD patients.

- Risk of significant weight gain as adjunct to antidepressant therapy: % of TRD patients experiencing ? 7% increase in weight.

- Delivery burden.

- Price/day.

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

- Effect on depressive symptoms in TRD patients.

- Long-term efficacy in TRD Patients.

- Time to onset of therapeutic effect.

- Risk of weight gain.

Physicians surveyed: 61 U.S. and 30 European psychiatrists.

Payers surveyed: 21 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)

- Vortioxetine (Lundbeck/Takeda Pharmaceutical’s Brintellix)

- Bupropion SR (GlaxoSmithKline’s Wellbutrin SR, generics) + antidepressant

Emerging Therapies

- Brexpiprazole (Lundbeck/Otsuka Pharmaceutical) + antidepressant

- Cariprazine (Actavis/Gedeon Richter/Mitsubishi Tanabe Pharma) + antidepressant

- ALKS-5461 (Alkermes) + antidepressant

- Amitifadine (Euthymics Bioscience)

- Rapastinel (formerly GLYX-13; Naurex)