Both agents attempt to address a relatively unmet need for effective prophylaxis against the CINV that occurs during the period from 24+ to 120 hours after higly-emetogenic chemotherapy is administered (Delayed Phase). Current 5-HT3 antagonists such as Zofran, Aloxi, and Kytril are available in generic forms and provide reasonable efficacy during the Acute Phase (0 to 24 hours after chemotherapy).
This report reviews the underlying rationale for NK-1 therapy, the available phase II rolapitant data and the probability of phase III success, the history of relevant precedents and the probability of regulatory success, and importantly, rolapitant’s ability to compete against Emend in the marketplace.
CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV):
2. Classification of emetic risk and therapy
1. Rationale for use
2. Post-operative nausea and vomiting
3. Phase II trial in CINV
4. Phase III trials
CLINICAL AND REGULATORY DISCUSSION:
1. Will the phase III trials show positive efficacy outcomes?
2. Are there safety concerns?
- Clinical data from the meta-analysis and from Emend seem to confirm a benign profile
- The pharmacology of NK-1 inhibition suggest benefit and risk
- Precedents also suggest some risks
- In summary
3. Will the rolapitant program provide adequate support for approval?
- General considerations
- The Emend precedent
2. Competitive analysis
APPENDIX 1. Risk of emesis with chemotherapeutic agents
APPENDIX 2. ASCO CINV treatment guidelines
APPENDIX 3. Therapy regimens used in rolapitant and Emend trials
APPENDIX 4. Rolapitant phase II CINV trial results: Cycle 1 complete response rates by dose and phase
APPENDIX 5. Treatment-emergent/related adverse events with =2% incidence during the phase II CINV rolapitant trial (all cycles)
APPENDIX 6. Percent of patients with adverse events in the two pivotal oral regimen emend trials combined: cycle 1, hec setting, incidence =3%