Back From The Brink: Genmab's Arzerra Win's CLL Approval And Cash From Partner GSK

Danish biotech set back by an earlier failure in non-Hodgkin's lymphoma plans new studies with a $23 million milestone payment from partner GSK.

Genmab won't have to chance approaching capital markets for funding to conduct additional Phase III studies for its blood cancer drug Arzerra now that the anti-CD20 monoclonal antibody has won FDA approval for treatment of refractory chronic lymphocytic leukemia.

With the approval - Genmab's first - comes a $23 million milestone payment from partner GlaxoSmithKline, and the Danish biotech plans to cash the check immediately. "The invoice is being raised today," Genmab's chief financial officer, David Eatwell, confirmed during an Oct. 27 analyst call.

GSK plans to execute the launch in the next few weeks. For CLL, Arzerra (ofatumumab) is priced at $4.40 per milligram, or $98,120 for a six-month course of therapy, Genmab CEO Lisa Drakeman said. For patients who are low-income, uninsured or underinsured, GSK has added the drug to its Patient Assistance Program. Planned future indications will require a smaller dose, so treatment is likely to cost in the $27,720 to $36,520 range at current pricing levels, certainly "at parity with other treatment options," Drakeman said.

Back from the brink

Genmab also is investigating Arzerra for use in the much larger indication of rituximab-refractory follicular non-Hodgkin's lymphoma. But a disappointing response rate in Phase II testing announced in August meant no milestone payment from GSK, and progress on the indication has been stymied.

The biotech was faced with the possibility of approaching the capital markets for funding. Analysts even went so far as to suggest GSK might opt to buy out its partner in order to advance the drug (Also see "Arzerra Disappoints In NHL, Putting Genmab On Shaky Ground" - Pink Sheet, 24 Aug, 2009.).

Now, with that bullet dodged, Genmab expects to provide details of a head-to-head study comparing Arzerra with standard-of-care rituximab (Genentech/Biogen Idec's Rituxan ) shortly, Drakeman said. The risky and expensive trial is thought to be necessary for gaining approval and subsequent market traction in NHL.

The firm plans to report data from Arzerra trials, including the refractory NHL study, at the American Society of Hematology meeting in New Orleans this December. It also has applied to present data from the failed NHL study as a late-breaking abstract.

Accelerated approval after AC nod

On May 29, FDA's Oncologic Drugs Advisory Committee voted 10-3 that the objective response rate seen in a single-arm Phase II trial of Arzerra was likely to predict clinical benefit and thus support accelerated approval in CLL patients refractory to fludarabine and alemtuzumab (Genzyme's Campath ), which is the labeling Genmab got for the drug (Also see "Murky Response Measures Shouldn’t Block Accelerated Approval Of GSK’s Arzerra, ODAC Says" - Pink Sheet, 29 May, 2009.).

In the study, 42 percent of patients with CLL who were refractory to both the other drugs responded to treatment with Arzerra. They had a median duration of response of 6.5 months.

Ofatumumab is an immunotherapeutic or therapeutic vaccine that triggers the body's immune response to attack cancerous B-cells. The MAb binds to a membrane-proximal small loop epitope on the CD20 molecule on B-cells, a different binding site from other marketed anti-CD20 MAbs, such as Rituxan.

The most common serious adverse reactions were infections, including pneumonia and sepsis, neutropenia and pyrexia. In its release, FDA cautions that the infection danger extends to progressive multifocal leukoencephalopathy, a dangerous brain infection associated with immunosuppressant therapies.

On the call, Genmab Chief Scientific Officer Jan van de Winkel stressed that PML has been associated with only one patient on Arzerra and that the patient was heavily pretreated with chemotherapeutic drugs that affect the number of CD4 T-cells, which are associated with PML.

Accelerated approval based on a surrogate endpoint, in this case objective response rate, is predicated on further study of the drug. Genmab currently is conducting a clinical trial in CLL patients to confirm that the addition of Arzerra to standard chemotherapy delays the progression of the disease.

Other pipeline options

In July, Genmab and GSK announced that Arzerra had met its primary endpoint in a phase III study of patients with rheumatoid arthritis who had an inadequate response to methotrexate. The biologic also is in Phase II against multiple sclerosis.

The RA data "are very robust and also good," van del Winkel said during the call. He said more data would be released at an upcoming rheumatology meeting.

Meanwhile, Genmab's unpartnered HuMax-EGFr antibody zalutumumab is in Phase III studies against head and neck cancer. During the call, Drakeman noted that data anticipated by the end of 2009 will be delayed until possibly first-quarter 2010 because "the patients have obviously lived longer than we expected."

Patient survival in this case is a mixed blessing because the delayed close of the trial means delayed partnering of the drug. However, Drakeman said the company has no immediate plans to raise new funding. "Of course, a biotech executive will never say never on that score," she said, adding that "we have a nice pipeline, and we can potentially put some money to use. But there is no express or immediate plan."

The company will have about $200 million in cash at the end of 2009, Eatwell said, noting Genmab will report earnings again on Nov. 10.

Neither does the firm plan to scale down any current programs. In addition to the GSK partnership and in-house programs, the biotech is engaged with Roche in a number of drug-development projects, including RG1507, in Phase II against several solid tumor cancers.

-Shirley Haley ([email protected])