BioWorld Today Correspondent

Genmab A/S passed its most significant milestone to date by obtaining its first drug approval, for ofatumumab (Arzerra) as a therapy for patients with chronic lymphocytic leukemia (CLL) who are refractory to fludarabine and alemtuzumab (Campath).

The approval triggered a milestone payment of DKK116 million (US$23.1 million) from its development partner, London-based GlaxoSmithKline plc.

The FDA granted Genmab, of Copenhagen, Denmark, and GSK accelerated approval, based on a Phase III trial in which 42 percent of double-refractory CLL patients responded to therapy, with a median duration of response of 6.5 months.

The approval contained no surprises, Genmab CEO Lisa Drakeman told BioWorld Today. "It's exactly as discussed at the cancer advisory meeting this summer," she said. The FDA's Oncology Advisory Committee (ODAC) voted 10-3 in favor of approving the drug in double-refractory patients in late May.

"We assume the approval does not allow for use in patients refractory to fludarabine but ineligible for alemtuzumab, and is thus a somewhat smaller patient population than originally envisaged," Richard Parkes, senior analyst at PiperJaffray, in London, wrote in a research note.

One case of the brain infection progressive multifocal leukoencephalopathy (PML) was reported during the development program, but that has not been unambiguously attributed to the drug. The FDA label does not contain a black-box warning on PML, Drakeman said, although a press release issued by the agency stated: "The most serious side effects of Arzerra are increased chance of infections, including progressive multifocal leukoencephalopathy, a brain infection that is generally fatal."

Ofatumumab, an anti-CD20 monoclonal antibody, will become available to CLL patients in the coming weeks. It does not come cheap. At a cost of $4.40 per milligram, a six-month course of therapy, involving 22,300 milligrams of drug, will cost $98,120, Drakeman said on a conference call Tuesday.

GSK is putting in place a patient-assistance program for low-income or underinsured patients. Other indications for which the two companies are seeking approval - such as non-Hodgkins lymphoma (NHL) and rheumatoid arthritis - will be less expensive, with total costs ranging from $27,720 to $36,520.

Neither of those additional programs has a straightforward path to approval, however. In NHL patients refractory to another anti-CD20 antibody, rituximab (Rituxan), ofatumumab achieved a response rate of 11 percent in a Phase III study. "While the response rate was not what we were looking for, the overall data are not unlike other data in other refractory cancer indications with other products," Drakeman said.

In rheumatoid arthritis, a large-scale safety study is required for approval, but the compound's competitive profile vs. TNF-alpha inhibitors has been questioned.

Shares in Genmab (COPENHAGEN:GEN) closed at DKK142.75 Tuesday, up DKK5.75, or 4.2 percent, having peaked during early trading at DKK149. "We do not expect this to be sustained until Genmab can deliver a clear strategy for expanding on Arzerra's initial limited indication within a reasonable time frame," Parkes wrote. Until then the stock is "more attractive" in the DKK100 to DKK120 range, he stated.

The additional milestone payment takes Genmab's total milestone income from its alliance with GSK to DKK868 million (US$172.6 million). The total potential value of the deal is around DKK12 billion, including an up-front payment of DKK1.085 million, which Genmab is recognizing over a five-year period.