Roche on Thursday announced the first results from the late-stage CLL11 study, showing that GA101 in combination with chemotherapy demonstrated a significant 86 percent reduction in the risk of disease progression, relapse or death in elderly patients with chronic lymphocytic leukaemia (CLL). The company noted that based on the data, marketing applications have been filed in Europe and the US, where the FDA has granted the drug, also known as obinutuzumab, breakthrough therapy status.
The trial randomised 781 previously untreated elderly people with CLL and comorbidities to receive either GA101 or MabThera (rituximab), also known as Rituxan, both in combination with chemotherapy, or chemotherapy alone. Results of an analysis that included 589 patients showed that median progression-free survival (PFS) was 23 months for patients who received GA101 plus chemotherapy, compared to 10.9 months in those given chemotherapy alone. Further data demonstrated that the overall response rate was 75.5 percent for GA101 plus chemotherapy, versus 30.2 percent for chemotherapy alone, while 22.2 percent who received Roche's experimental drug had a complete response, compared to no patients receiving chemotherapy alone.
The company noted that data showing the actual survival benefit will not be available for some time. Lead investigator Valentin Goede added "we have to wait for longer follow-up to comment on duration of control of the disease." However, he said "these are encouraging results," suggesting that PFS for GA101 was likely to improve.
Another arm of the trial, for which data will not be available until late this year or in 2014, is comparing GA101 directly with MabThera. Results showed that those given MabThera plus chemotherapy had a median PFS of 15.7 months, an overall response rate of 65.9 percent and 8.3 percent of patients had a complete response. "After the data are presented at [the ASCO meeting] we’ll have a new view of the potency of this drug," remarked Niko Andre, Roche’s global head of medical affairs.
Deutsche Bank analyst Tim Race said that "in theory [GA101 is] a smarter-designed version of Rituxan." However, he noted that "the problem is that Rituxan is a brilliant drug, and being better than a brilliant drug is always difficult." Combined global sales of MabThera and Rituxan, which Roche markets with Biogen Idec, reached 6.7 billion Swiss francs ($7 billion) last year. However, patents on the drug expire in Europe at the end of this year and in the US in 2018 and Roche is hoping that GA101 will help the company fend off competition from biosimilar versions of MabThera (for related analysis, read ViewPoints: Roche CEO Schwan – Biosimilars part of pharma's "contract with society").
Goede noted that in the CLL11 study, GA101 had a far higher incidence of neutropenia than either MabThera or chemotherapy alone. Results showed that 34 percent of patients taking the experimental drug developed neutropenia, versus 25 percent and 15 percent of those given MabThera and chemotherapy alone, respectively. However, Goede said the safety profile of GA101 was acceptable because the neutropenia did not lead to infections or fever.
Infusion-related reactions were also seen with the first dose of GA101, which were not seen with chemotherapy. Researchers said this was managed by splitting the first dose of the drug over two days. Goede indicated that there had been a similar issue in early clinical trials of MabThera, adding "this is a problem that can be fixed." Roche is also investigating GA101 in patients with non-Hodgkin’s lymphoma.
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