Pharmion Preps For MDS Competition; Vidaza Dosing Under Study

Pharmion is testing more convenient dosing schedules for its myelodysplastic syndromes drug Vidaza (azacitidine) ahead of potential market entry of competitors in the fall.

The company expects studies evaluating three alternative Vidaza dosing schedules will be completed by year-end, CEO Patrick Mahaffy said May 17 at the Banc of America Securities Conference in Las Vegas.

Pharmion's MDS therapy is labeled for a first-cycle treatment of 75 mg/m² subcutaneously for seven days. The company is testing what could be marketed as a more convenient dosing regimen: a "drug holiday" over the weekend.

Most physicians have already adopted that schedule, according to Pharmion.

"What we've seen is the majority of physicians, if not the vast majority of physicians, using it five days in a row, taking the weekend off, and then Monday, Tuesday," Mahaffy said. "One of our studies is looking at the regimen, making sure that that's appropriate and that the data would be reasonable."

Pharmion is also studying a 10-day schedule at a lower dose (50 mg/m²), with a break over the weekend. A third option would be most convenient for the patient and physician: a five-day schedule at 75-100 mg/m².

Since Vidaza's May 2004 approval, Pharmion has enjoyed the product's status as the only drug treatment approved for MDS. Vidaza posted sales of $47.1 mil. in 2004, representing approximately 36% of Pharmion's total revenue.

Pharmion licensed azacitidine from Pharmacia (now Pfizer) in June 2001 and used proceeds from its initial public offering to fund pivotal studies (¹ (Also see "Pharmion IPO To Fund Vidaza Accelerated Approval For Bone Marrow Disorder" - Pink Sheet, 1 Sep, 2003.), p. 24). Pharmion pays Pfizer a royalty equal to 20% of Vidaza sales.

Two competitors to Vidaza could be approved by FDA this fall: MGI's Dacogen (decitabine) and Celgene's Revlimid (lenalidomide, formerly Revimid ).

The Dacogen NDA has a PDUFA date of Sept. 1, and Revlimid's estimated user fee deadline is Oct. 8.

Dacogen demonstrated superior efficacy in one arm of an uncontrolled trial conducted at the University of Texas M.D. Anderson Cancer Center. Results were presented during the May 13-17 American Society of Clinical Oncology's annual meeting.

Preliminary results show a complete response rate of 47% when Dacogen is given as a 20 mg/m² I.V. over one hour daily for five days; 24% when given 10mg/m² I.V. over one hour daily for 10 days; and 29% when given 10 mg/m² subcutaneously twice daily for five days.

Dacogen's dosing regimen in the NDA is a three-hour, 15 mg/m² infusion administered three times a day for three days (² (Also see "MGI Dacogen Dosing Strategy Will Consider Reimbursement, Convenience" - Pink Sheet, 7 Mar, 2005.), p. 31).

Results from the M.D. Anderson study indicate greater Dacogen efficacy with the five-day dosing schedule. In the pivotal trial submitted with the NDA, Dacogen demonstrated a 9% complete response rate and a 17% overall response rate when added to supportive care. Vidaza has a 15.7% overall response rate in labeling.

Pharmion's Mahaffy questioned the M.D. Anderson data during the Banc of America conference. "Single institution studies are never widely accepted or believed by practicing physicians, even after you duplicate it in another large study," he said. In addition, "the side effect profile for this was serious."

"We know how to counter-detail with that type of data," he declared.

During a same-day presentation at the Banc of America conference, MGI CEO Lonnie Moulder defended the data. "The work done at M.D. Anderson fits what we see in other trials."

The five-day I.V. infusion is the "most tolerated way to give the drug," which means "patients will get the drug on time and they'll get the full dose of the drug," he said. Furthermore, "this regimen actually has a pharmacologic basis for being a better regimen."

Based on the user fee deadlines, Revlimid is likely to be approved after Dacogen. Revlimid has shown particular efficacy among the MDS subpopulations of patients with the chromosome 5q31.1 deletion.