Researchers Detail Favorable Zevalin Data At ASH, But Also Medicare Concern
The Pink Sheet Daily. 2007 Dec 17, J. Salodof MacNeil, G. Twachtman
ATLANTA - No sooner did Medicare announce it will cap funding for two approved radioimmunotherapies than an international phase III trial is reporting that one of them, Zevalin, can prolong progression-free survival by two years in relapsed follicular non-Hodgkin's lymphoma.
The Medicare reimbursement change would apply to both Zevalin and Bexxar.
According to data presented during the American Society of Hematology's Dec. 8-11 annual meeting, patients given first-line consolidation therapy with Zevalin (90Y-ibritumomab tiuxetan) have so far achieved a median progression-free survival of 37 months compared with 13.5 months in a control group that had no further treatment after achieving a complete or partial response with first-line therapy (P less than .001).
Overall survival data are not yet mature, Anton Hagenbeek, study investigator and professor of hematology at University Medical Center Utrecht/HOVON in the Netherlands, said during a press briefing at ASH to discuss the results.
The Zevalin First-Line Indolent Trial enrolled 414 patients who had responded to various first-line therapies for relapsed follicular non-Hodgkin's lymphoma at 77 centers in 12 European countries and Canada. A total of 208 patients were randomized to a consolidation regimen of rituximab (Biogen Idec's Rituxan) and Zevalin, while 206 received standard therapy, which is no further treatment, Hagenbeek said.
Other favorable findings in the Zevalin arm include at approximately 2.5 years of follow-up: a 77 percent rate of conversion from partial responses after induction therapy to complete responses, a complete remission rate of 87 percent, and a molecular remission rate of 97 percent.
Hagenbeek described the consolidation regimen as well tolerated with no unexpected toxicities and noted that the conversion rate was the same regardless of the first-line therapy received before the patient was randomized.
Bayer Schering Pharma AG in Germany sponsored the trial. It has exclusive worldwide rights to Zevalin except in the U.S. Biogen Idec had been marketing Zevalin in the U.S. under a collaboration with Bayer; Cell Therapeutics in August signed an agreement to acquire those rights from Biogen Idec.
CTI said at that time it plans to initiate two clinical trials evaluating the use of Zevalin in front-line lymphoma settings to drive revenues of the product. The company purchased the rights to the radioimmunotherapy for $10 million in cash upfront and an additional $20 million in milestone payments if the product receives approval for a first-line indication in NHL, as well as royalties on sales.
CTI projects Zevalin could reach a positive cash flow position in 2010 and that peak sales of the drug could reach $250 million in the 2012 to 2014 timeframe, the company said in August. The deal is expected to close around year's end.
Zevalin is indicated for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed forms of B-cell NHL, including patients with rituximab-refractory follicular NHL. A competing radioimmunotherapy agent, GlaxoSmithKline's Bexxar (tositumomab), has a similar indication.
Treatment Given In Limited Number Of Facilities
Despite favorable clinical trials, both radioimmunotherapies are considered underused by practitioners. Each combines a monoclonal antibody to an antigen expressed on cancer cells with radiation, thereby enhancing the effects of radiation and immunotherapy. Both therapies must be given in a hospital with nuclear medicine capabilities. As a result, only a limited number of facilities, typically in academic centers, can deliver these therapies.
This can create a logistical roadblock to treating more patients with the drug. Lymphoma Research Foundation Chairman Oliver Press explained "there is a transfer of care and treatment that has to happen" from a general oncologist to a nuclear medicine physician or a radiation oncologist.
"That, for a variety of reasons, is awkward and time-consuming, and some are afraid they are going to lose their patient," Press said in an interview with "The Pink Sheet" after the ASH meeting.
Press also chairs the Fred Hutchison Cancer Research Center in Seattle.
Medicare Reimbursement Cap Set For 2008
As of Jan. 1, 2008, Medicare will set hospital payments at approximately $21,850 for Zevalin and $16,200 for Bexxar, which are administered only once.
The policy is contained in rules published Nov. 27 to update Medicare Part B reimbursement for hospital outpatient departments. Certain therapies, such as Zevalin and Bexxar, are reimbursed outside of the standard average sales price plus 5 percent amounts for hospital outpatient departments ("The Pink Sheet" Nov. 5, 2007, p. 32).
In 2007, the drugs were reimbursed based on claims data submitted by individual hospitals for the acquisition, handling and preparation of the radioimmunotherapies. As a result, there is no single flat rate for 2007 to compare with the 2008 payment ceiling, but many individual providers say they face cuts under the 2008 policy.
When asked about the Medicare decision, Hagenbeek said he is "a believer in coming up with good data" that can convince payers to invest in health care treatments. "I am happy that I work in Europe," he added.
The ASH press conference moderator, Jane Winter, a professor of medicine at Northwestern University in Chicago, said she had just learned that the new Medicare rates would be $10,000 less than it costs her hospital to provide radioimmunotherapy to lymphoma patients.
GSK said it submitted data to CMS showing that Bexxar's acquisition cost was $26,780.
"Just at the time that data are emerging to show this is highly effective, we are being cut off at the knees," Winter said, emphasizing that the treatments might not be offered at nonprofit hospitals such as Northwestern, because such facilities cannot afford to lose $10,000 for each patient treated.
Winter said the cost is attributable largely to the extensive technical support required and not the price of the agents themselves. "When you are dealing with radioisotopes, you don't want to cut your technical support," she said.
In the long term, the cost of alternative consolidation treatments could prove more expensive than the radioimmunotherapies, Winter added in an interview. "It's absolutely going to be cheaper" to administer radioimmunotherapies, she said, noting that FIT patients required no further treatments during the additional two years of progression-free survival, and comparing one-time treatment with Zevalin or Bexxar to an estimated $40,000 for just four weeks of rituximab.
But while clinicians, medical societies and manufacturers have been vocal on the subject, hospitals appear to have been quiet on the subject.
"One of our problems has been that hospitals have not been ... [vocal that] this is an issue for them," said Denise Merlino, coding advisor for the Society of Nuclear Medicine. "If they don't complain about being underpaid, then we have a tougher fight. It is kind of hard to get something fixed when it's only the societies that are complaining about it."
Advocacy Groups Target CMS
Lymphoma advocacy groups are already organizing to fight the increase, according to Winter, who noted that she had conducted a number of Zevalin studies sponsored by Biogen. Although NHL is the fifth most common cancer, she observed that advocates "just don't have the clout of the colorectal cancer and breast cancer lobbies."
"We were hoping this study would give a real boost for use of radioimmunotherapy," she said.
Press sees the greatest potential for change coming from working with CMS on the issue, even though there has been a concerted effort to raise awareness of the issue in Congress.
"I have a feeling this issue will get lost in that larger push" to develop comprehensive Medicare reform legislation in Congress, Press said. "I haven't heard anyone who is terribly optimistic that that's going to be the most effective approach."
In the meantime, Press said the current strategy is to continue to pressure CMS into revisiting the reimbursement-setting methodology.
[Editor's note: Parts of this story were reported from the ASH meeting in Atlanta by Jane Salodof MacNeil, Senior Editor, Elsevier Global Medical News]
oncologystat.com |
