Celgene, Pharmion Plummet On Positive Velcade Data

Washington Editor

While new study data for their multiple myeloma therapies was positive for Millennium Pharmaceuticals Inc., Celgene Corp. and Pharmion Corp., the later two firms took a hit Monday on Wall Street.

Shares of Cambridge, Mass.-based Millennium (NASDAQ:MLNM) rose 92 cents, or 6 percent, to close at $15.99, while shares of Summit, N.J.-based Celgene (NASDAQ:CELG) plummeted 14.3 percent, or $8.18, to close at $49.18.

Shares of Boulder, Colo.-based Pharmion (NASDAQ:PHRM), which is being acquired by Celgene in a $2.9 billion deal, fell $3.35, or 5.3 percent to close at $60.32.

The study results of Millennium's Velcade, Celgene's Revlimid and Pharmion's thalidomide were presented at this year's American Society of Hematology (ASH) meeting in Atlanta.

Revlimid (lenalidomide), an analogue of thalidomide, is approved in the U.S. as a treatment for multiple myeloma in combination with dexamethasone for patients who have received at least one prior therapy and a certain anemia-related condition. The drug also is approved in the European Union and Switzerland.

Under its acquisition of Pharmion, Celgene will reacquire the worldwide rights to thalidomide, which is sold by Celgene in the U.S. under the brand name Thalomid as a therapy for moderate-to-severe erythema nodosum leprosum, a painful skin condition associated with leprosy, and multiple myeloma. (See BioWorld Today, Nov. 20, 2007.)

Pharmion's marketing authorization application with the European Medicines Agency (EMEA) for thalidomide as a therapy for untreated multiple myeloma is pending.

The firm also submitted an application to the EMEA in January to market thalidomide in combination with melphalan and prednisone as a first-line treatment of patients with untreated multiple myeloma, age 65 years or older or ineligible for high-dose chemotherapy.

Pharmion's thalidomide product is approved in Australia, New Zealand, Turkey, Israel, South Korea and Thailand for the treatment of multiple myeloma after the failure of standard therapies.

Millennium's Velcade (bortezomib) is approved in the U.S. for the treatment of patients with multiple myeloma who have received at least one prior therapy. It also is indicated for the treatment of patients with mantel-cell lymphoma who have received at least one prior therapy. In the European Union, Velcade is approved for patients with multiple myeloma after first relapse.

Millennium is co-developing Velcade with Johnson & Johnson Pharmaceutical Research and Development LLC.

Interim results from a 256 patient, multicenter, randomized Phase III clinical trial of Velcade combined with thalidomide and dexamethasone (the VCTD arm) showed a fourfold increase in complete remission for patients with previously untreated multiple myeloma compared with thalidomide and dexamethasone alone (the TD arm), the current standard of care in the U.S.

As induction therapy prior to stem cell transplantation, the VcTD arm demonstrated a complete remission rate of 36 percent compared with 9 percent in the TD arm, investigators reported. Following transplantation, the VcTD arm demonstrated a complete remission rate of 57 percent compared with 28 percent in the TD arm. Successful stem cell mobilization occurred in more than 90 percent of patients in both arms, researchers reported.

Results from a 482 patient, multicenter, randomized Phase III clinical trial comparing Velcade and dexamethasone (the VcD arm) with vincristine, adriamycin and dexamethasone (the VAD arm) demonstrated that patients in the VcD arm had a complete remission rate of 21 percent compared with 8 percent with VAD. Of the 404 patients who proceeded to stem cell transplantation, the VcD arm demonstrated a post-transplantation complete remission rate of 41 percent compared with 29 percent of patients in the VAD arm.

Also reported at ASH were results of a Phase III trial evaluating the combination therapy of Revlimid and dexamethasone in patients with newly diagnosed multiple myeloma that showed patients given the treatment regimen had superior response rates and progression-free survival compared with those who received dexamethasone alone.

Overall response rate in patients receiving Revlimid and dexamethasone was 85.3 percent with 22.1 percent of patients achieving complete responses compared with 51.3 percent and 3.8 percent, respectively in the dexamethasone only group. In addition, estimated one year progression-free survival was 77 percent in patients who received the combined therapy compared with 55 percent who received dexamethasone alone.

Investigators reported that the one-year overall survival rates in both arms of the study are among the highest ever reported, 93 percent and 91 percent, influenced by the fact that patients in the dexamethasone-only arm crossed over and received Revlimid and dexamethasone, at the time of progression or when the study was halted.

Pharmion reported that final data from a 232 patient, randomized, double-blind, placebo-controlled Phase III trial demonstrating the addition of thalidomide to standard treatment of melphalan-prednisone (the MP-T arm) improved survival by 17.6 months in patients 75 or older with newly diagnosed multiple myeloma compared with melphalan-prednisone (the MP-placebo arm) alone.

The median overall survival in the MP-T arm was 45.3 months compared with 27.7 months for patients in the MP-placebo arm. Median progression-free survival was significantly higher in the MP-T arm, 24.1 months, compared with 19 months for the MP-placebo arm, investigators reported.

Pharmion also presented results from a Phase III multicenter, international, randomized study of Vidaza (azacitidine for injection) in the treatment of patients with higher-risk myelodysplastic syndromes (MDS).

Results showed that Vidaza provides a significant survival benefit compared with conventional care regimens (CCR) in higher-risk MDS patients. The median overall survival advantage for Vidaza-treated patients compared with CCR-treated patients was 9.4 months.

Also at ASH, Pharmion and Montreal-based MethylGene Inc. reported data from two ongoing Phase II studies with MGCD0103, the companies' novel, isotype-selective histone deacetylase inhibitor, as a single agent in the treatment of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).

Results from the first trial suggested that single-agent MGCD0103 showed significant antitumor activity in relapsed/refractory classical HL and is well tolerated, with dose modifications used as necessary to manage toxicities. An 85-mg dose is continuing to be evaluated in this patient population.

Of the 21 evaluable patients who received the 110-mg starting dose, 38 percent showed objective responses of two complete responses and six partial responses. The overall disease control rate was 43 percent, researchers said. Tumor reductions were observed in 86 percent of patients who had CT scans and 57 percent of the patients experienced tumor shrinkages greater than 30 percent.

Results from the second study suggested that single-agent MGCD0103 demonstrated significant anticancer activity in relapsed and refractory NHL and has a manageable side effect profile.

The ASH conference continues Tuesday. n