May 9 2007 1

Disclosures

• Philip L. McCarthy Jr. BMT Program Roswell Park Cancer Institute, Buffalo, NY– Participated in Dor Pharma acute Graft-versus-Host

Disease (GvHD) Phase III study examining beclomethasone diproprionate (BDP)

– Involved in the design of future large chronic GvHD study

– Asked by BMC Communications Group, LLC if I would speak regarding the RPCI experience with BDP

– Paid for travel myself

May 9 2007 2

Iyer et al Long-Term Use of Oral Beclomethasone Dipropionate (BDP) for the Treatment of Gastrointestinal (GI) Graft-versus-Host Disease (GvHD). Biology of Blood and Marrow Transplantation 11:587-592, 2005 • Investigational New Drug (IND) application for each

patient and cross-referenced originally with Enteron IND• RPCI BMT program interest in BDP use long-term for

chronic GvHD of the GI tract• Used BDP as capsule from Enteron as well as compounded

in corn oil and later in capsules• BDP was used for the treatment of acute and chronic GI

GvHD that was refractory to front line immunosuppressive therapy (calcineurin inhibitor and methylprednisolone 1-2 mg/kg/day or equivalent) or unable to wean or tolerate steroids without a GI GvHD flare

• BDP used as a systemic “steroid-sparing” agent

May 9 2007 3

Characteristic Responders Non-Responders

Median Age (range) 34 (5-51) 46.5 (6-53)

Refractory GvHD

Acute 0 2

Chronic 9 4

BDP Start, Med (range) days after BMT

431 (265-1529) 113 (39-251)

Med Steroid Dose at BDP start

19 (0-88) 113 (5-188)

# Cycles (range)

[28 days]

3 (1-20) 2 (1-5)

Patient Results, Iyer et al BBMT. 11:587-592, 2005

May 9 2007 4

Patient Steroid Dose pre-BDP (mg/d Methylprednisolone (MP) equiv)

Steroid Dose post-BDP (mg/d MP equiv)

% Change in Steroid Dose

1 (CR) 19 0 -100

2 (CR) 88 0 -100

3 (CR) 8 0 -100

1 (PR) 25 5 -79

2 (PR) 10 10 0

3 (PR) 30 0.5 -98

4 (PR) 0 0 NA

5 (PR) 75 75 0

6 (PR) 10 10 0

1 (NR) 113 238 +111

2 (NR) 5 53 +950

3 (NR) 88 463 +428

4 (NR) 138 88 -36

5 (NR) 188 38 -80

6 (NR) 113 113 0

Patient Characteristics, Iyer et al BBMT. 11:587-592 (2005)

May 9 2007 5

BDP use at RPCI

• Pharmacy-compounded at present• We would prefer a standardized formulation that would allow for

upper and lower GI tract exposure• We have used BDP in over 30 GI GvHD patients with a response

(decreased immunosuppression) in approximately 60% of patients• Well tolerated in long-term use• BDP blunts ACTH stimulation test adrenal response but does not have

the systemic effects of standard steroid therapy– Is this due to the liver first pass effect with metabolites that do not result

in symptomatic adrenal suppression?• BDP is the only drug added to steroids for upfront therapy of acute

GvHD that generates a superior outcome. Most immunosuppressive drugs added to steroids result in worse or equivalent outcomes

• BDP is useful therapy for acute GvHD and potentially for chronic GI GvHD (to be studied)