# Presentation: 267439

## PULMINIQTM(cyclosporine, USP) Inhalation SolutionBenefit-Risk/Conclusions

- Stephen Dilly, MD, PhD
- Chief Medical OfficerChiron | BioPharmaceuticals

## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

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## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

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## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

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## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

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## The Case for Approval of CyIS  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS, but some outstanding questions remain
- 	Approval of CyIS is warranted, with appropriate postapproval commitment

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## Postapproval Questions

- Outstanding questions
- How to give CyIS
- Duration of therapy
- Practical considerations of delivery
- Increase precision of survival benefit
- Survival, rejection, lung function
- Optimization of treatment regimen
- Further exploration of safety profile
- Detection of low-frequency safety signals

## Postapproval Commitment

- Open-label, multinational study using contemporary prospective matched controls
- 250 patients treated with CyIS
- 300 mg CyIS or maximum tolerated dose (MTD), prolonged treatment (5 years)
- Placebo control not appropriate or necessary
- > 1000 matched controls from UNOS database
- Contemporaneous controls receiving standard-of-care without CyIS
- Efficacy endpoints
- Primary: chronic rejection-free survival
- Secondary: all-cause mortality and change in FEV1
- Safety endpoints
- Infections requiring hospitalization, renal dysfunction, malignancy

## Conclusion  

- Lung transplant is a small, well-defined population
- Significant unmet need in lung transplantation
- Strong evidence for benefit
- Sound scientific rationale for CyIS
- Robust survival advantage
- Small risk of harm
- 	Lung transplant patients will live longer with CyIS
- 	Outstanding questions **can be addressed** with a postapproval study
- 	**Approval of CyIS is appropriate now**

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