Staff Writer

Despite the lack of major stock-moving news at this year's American Society of Hematology annual meeting, the conference provided plenty of posters, presentations, plenary sessions, exhibits, and company-sponsored events to keep attendees hopping.

Competitors become Companions

Last year's ASH meeting was rife with debate over the role of Millennium's Velcade (bortezomib) and Celgene Corp.'s Revlimid (lenalidomide) in the first-line treatment of multiple myeloma. But this year, Sundar Jagannath, chief of the multiple myeloma program at St. Vincent's Comprehensive Cancer Center in New York, said new data highlighting the benefits of combination treatment made such arguments "somewhat of a moot point."

A Phase I trial of Velcade and Revlimid plus dexamethasone and cyclophosphamide in previously untreated multiple myeloma achieved a 100 percent response, with 36 percent of patients achieving a complete response. And in the relapsed/refractory setting, a Phase II study showed Velcade and Revlimid plus dexamethasone induced an 86 percent response rate in the 63 evaluable patients, with 24 percent achieving a complete response.

Drugs seeking to improve on Velcade and Revlimid also had good ASH data in the relapsed/refractory multiple myeloma setting. Proteolix Inc.'s Velcade-competitor carfilzomib induced a response in 26 percent of the 39 patients in its single-agent Phase II trial, while Celgene's next-generation immunomodulator pomalidomide plus low-dose dexamethasone induced disease improvement or stabilization in 76 percent of patients in a Phase II trial.

Other new agents looked to combine with the current multiple myeloma standards. Keryx Biopharmaceuticals Inc.'s Akt-modulator perifosine (KRX-0401) induced a response in 38 percent of the 72 patients in its Phase I/II Velcade combo trial, while a Phase I Revlimid combo trial achieved a 70 percent response. And Gloucester Pharmaceuticals Inc.'s histone deacetylase (HDAC) inhibitor romidepsin induced a response in 85 percent of the 20 patients in its Phase I/II Velcade combo trial.

Combos May Emerge in Myelofibrosis

In the myelofibrosis field, Stanford Group Co. Analyst Han Li wrote in a research note that Incyte Corp.'s INCB424 is "well ahead of competing JAK2 inhibitors," with pivotal trials expected to begin next year. Phase II data presented at ASH showed the drug improves splenomegaly and a variety of constitutional symptoms.

Earlier in the JAK2 pipeline, Exelixis Inc. said a Phase I study of XL019 showed reductions in spleen size, leukocytosis, anemia and constitutional symptoms in certain patients, while TargeGen Inc. said a Phase I trial of TG101348 demonstrated a dose-dependent reduction in spleen size.

But Jefferies & Co. Inc. analyst Eun Yang said in a research note that while some JAK2 inhibitors can reduce enlarged spleens, most can't improve hematologic parameters. On the other hand, drugs like Celgene's pomalidomide and Eisai Corp.'s Dacogen (decitabine) improve hematologic parameters but not spleen size, Yang wrote. "Given the importance of improving both future studies could potentially involve combination therapy," Yang predicted.

Elsewhere on the Dacogen front, full results presented at ASH from the European Phase III study in myelodysplastic syndromes showed disappointing survival and tolerability. Analysts noted that the data likely will benefit competitor Vidaza (azacitadine, Celgene) as both continue to compete for MDS market share.

No Shortage of Data from the Big Boys

Drugs for non-Hodgkin's lymphoma made a significant showing at ASH - in fact, there was so much data around Rituxan (rituximab, Genentech Inc. and Biogen Idec Inc.) that it was allotted its own section. Yet the biggest Rituxan buzz centered on data not in NHL but in the unapproved indication of chronic lymphocytic leukemia (CLL), where two Phase III trials demonstrated a significant increase in progression-free survival.

Another Rituxan CLL study to garner attention was a Phase II trial of the drug in combination with Cephalon Inc.'s CLL and NHL drug Treanda (bendamustine). The combo resulted in a 77.4 percent response rate in 62 relapsed CLL patients. The Rituxan/Treanda combo also garnered good data in NHL: Cowen and Co. analyst Rachel McMinn pointed to a study showing the combination has "equal efficacy, but better tolerability" than the Rituxan/chemotherapy regimen in first-line indolent NHL.

Revlimid, too, had data in both NHL and CLL. Celgene's NHL-003 study showed a 41 percent response rate in the subset of patients with mantle-cell lymphoma and a 29 percent response rate in the diffuse large-B-cell lymphoma subset, which Robert W. Baird & Co. analyst Christopher Raymond wrote "may help augment Revlimid's NHL uptake."

In CLL, Revlimid showed 52 and 65 percent responses in separate front-line studies, but McMinn noted that the "toxicity still needs watching."

Options for Peripheral T-cell Lymphoma

There may not yet be any treatments approved for peripheral T-cell lymphoma (PTCL), an aggressive subset of non-Hodgkin's lymphoma, but ASH highlighted several nearing the end of the pipeline.

Allos Therapeutics Inc. presented top-line data from a pivotal Phase II trial of pralatrexate (PDX) showing a 27 percent response rate and 11 complete responses in the trial's 109 heavily pretreated PTCL patients. Analysts predicted the data will be sufficient for approval, and the company plans to submit a new drug application in the first half of 2009.

Meanwhile Gloucester, which also has a pivotal PTCL trial underway, presented Phase II data showing that romidepsin induced a 44 percent response rate, with four of 34 evaluable patients classified as complete responders. Additionally, PharmaMar SA said a subset of PTCL patients in its Phase II Aplidin (plitidepsin) study achieved a 36 percent response rate. And Amgen Inc.'s CCR4-targeted antibody, which it licensed from Kyowa Hakko Kogyo Co. Ltd. in a potential $520 million deal earlier this year, was the subject of a Phase I poster showing that the drug induced a complete response in the only PTCL patient in the study.