Pharmion Corp.'s value soared 47.8 percent Thursday after the FDA issued full approval of Vidaza, the firm's orphan drug for myelodysplastic syndromes (MDS).
Vidaza was cleared for five MDS subtypes including refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation and chronic myelomonocytic leukemia, the company said.
Vidaza, which belongs to a class of drugs in development known as hypomethylating or demethylating agents, is believed to work by restoring normal growth and differentiation of bone marrow cells.
Pharmion's stock (NASDAQ:PHRM) jumped $12.91 Thursday to close at $39.91.
Patrick Mahaffy, president and CEO of Boulder, Colo.-based Pharmion, told BioWorld Today the company expects to launch Vidaza (azacitidine for injectable suspension) July 1 without seeking a partner.
Meanwhile, the "full approval" status of Vidaza is of particular interest to The Street because Pharmion submitted its new drug application under Subpart H (accelerated approval), which permits drug approval based on either evidence from adequate and well-controlled studies of the drug's effects on a surrogate endpoint that reasonably suggest clinical benefits, or on the drug's effect on a clinical endpoint other than survival, provided the company agrees to a confirmatory study. Pharmion does not have to complete its Phase III/IV confirmatory study under full-approval rules.
"This is a very surprising approval, a very surprising move by the FDA," Elemer Piros, senior biotechnology analyst with Rodman & Renshaw Inc. in New York, told BioWorld Today. "For this particular disease, it appears that the FDA has set the bar very low and [demonstrated] that it really wanted to provide a treatment for MDS patients."
Piros' comments reference Pharmion's Phase III study of 191 patients with all five types of MDS. The overall response rate was 15.7 percent in Vidaza-treated patients who didn't have acute myelogenous leukemia, or AML (16.2 percent for all Vidaza-randomized patients, including AML), compared to zero percent in the observation group (p<0.0001). Responses occurred in all five subtypes of MDS, as well as in patients determined to have a baseline diagnosis of AML, the company said. (See BioWorld Today, Dec. 30, 2003.)
Mahaffy said the mean and median duration of responses in the Phase III were 330 and 530 days, respectively.
"Vidaza can have a real benefit," he said. "In the high-risk MDS population, the average survival without therapy is less than one year, so we believe this could be a very important drug."
The FDA described MDS as a collection of disorders in which the bone marrow does not function normally and not enough normal blood cells are made. MDS might develop following treatment with drugs or radiation therapy for other diseases, or it might develop without any known cause. Some forms of MDS can progress to AML, a type of cancer in which too many white blood cells are made.
The NDA was based on an ongoing Phase III/IV confirmatory trial, an open-label, controlled Phase III trial, as well as two supportive Phase II trials. (The Cancer and Leukemia Group B conducted the Phase II and III studies, which were sponsored by the National Cancer Institute.)
Piros said many people are skeptical about whether the Phase III/IV ever will be completed because it will be difficult to enroll.
Mahaffy, however, told BioWorld Today the firm is committed to completing the study, yet he would not comment on how many patients have been enrolled.
The 350-patient confirmatory trial is designed to compare the effect of Vidaza vs. conventional-care options on survival in patients with high-risk MDS. The study is examining survival outcomes as well as secondary endpoints, and is being conducted mostly in Europe and Australia.
Piros expects Vidaza to cost about $32,000 per patient per year in the U.S. The estimated worldwide market is roughly $1.3 billion per year, including about $900 million in U.S. sales.
However, Piros cautioned that Pharmion will have to share the market with SuperGen Inc., the Dublin, Calif.-based firm developing an MDS candidate called Dacogen (decitabine). Piros expects SuperGen to begin filing its application in the next 30 to 40 days and to complete the application sometime in September. Under the best of circumstances, Dacogen could win approval in February or March. (While Dacogen and Vidaza are in the same class of drugs, they are different chemical entities, therefore each can maintain orphan status.)
Also, Celgene Corp., of Warren, N.J., has a Phase II MDS candidate called Revimid. Piros said Revimid would work best as a complementary product to Dacogen and Vidaza.
Pharmion acquired worldwide rights to Vidaza in an agreement with Pharmacia Corp., now part of Pfizer Inc., of New York. Pfizer will receive royalties on Vidaza's sales, Mahaffy said, adding that the company expects to seek approval in Europe during the second half of this year. Pharmion will not bring on a partner there, either.
In other business this week, Pharmion said it plans to provide additional clinical data and resubmit its application with the European Medicines Evaluation Agency for the use of Thalidomide Pharmion 50 mg to treat patients with multiple myeloma. The company is targeting a resubmission with additional clinical data from ongoing studies in both relapsed/refractory and newly diagnosed patients.
The company's guidance for its share of Thalidomide Pharmion sales in 2004 is $51 million to $56 million for named-patient and compassionate use, updated from previous guidance of $38 million to $43 million. Pharmion maintains its application in Europe for the use of Thalidomide Pharmion in the treatment of cutaneous manifestations of erythema nodosum leprosum, a condition associated with leprosy.
Thalidomide Pharmion is approved in New Zealand and Australia. Pharmion shares certain rights to the product with Celgene.