Ash 2017 – Mavoric sends Poteligeo US bound at last
Kyowa Hakko Kirin’s anti-CCR4 drug Poteligeo has recorded negligible sales in the niche indication for which it has been sold in Japan since 2012. This could be about to change if results of the Mavoric study, presented at Ash on Sunday, are anything to go by.
Presenters said Mavoric was the first pivotal cutaneous T-cell lymphoma trial to use progression-free survival as primary endpoint – a measure on which Poteligeo easily beat Merck & Co’s Zolinza. Stanford University’s Dr Youn Kim said Poteligeo had already been filed with the US FDA – importantly, in patients irrespective of CCR4 expression – and this could become its first approved use in the West.
This would be in contrast to the situation in Japan, where Poteligeo is available for relapsed or refractory adult T-cell leukaemia-lymphoma that specifically is CCR4-positive. Sales of the drug, which contains the active ingredient mogamulizumab, totalled just $18m last year.
Mavoric was said to have read out positively in April, but Kyowa had kept full data back until now. The trial has already been used to support a Japanese application to eliminate the need to test patients’ CCR4 expression, filed just two weeks ago.
2018 US approval?
In the US, “we hope [the drug] will be approved early next year”, Dr Kim told Sunday’s Ash press conference.
CCR4 is a chemokine receptor expressed on certain immune system cells, and its activation is thought to help malignant cells evade an immune response. But Dr Kim played down the importance of testing for it as a prerequisite of treatment for cutaneous T-cell lymphoma (CTCL), stating: “CCR4 is very consistently expressed in this population.”
Mavoric enrolled 186 subjects into a Poteligeo arm, while another 186 received Zolinza, Merck’s HDAC inhibitor, indicated for cutaneous manifestations of 3rd-line CTCL, as control.
Importantly, CCR4 expression was not an inclusion criterion for enrolment. Intriguingly, progressing Zolinza patients were allowed to cross over to Poteligeo treatment, but not the other way around.
Median PFS was 7.7 months for patients treated to progression with Poteligeo, versus 3.1 months for those on Zolinza, with risk of progression cut by 47%, to a high level of statistical significance (p<0.0001). Overall response rate was 28.0% versus 4.8% for Zolinza, which Dr Kim called “highly superior”.
However, this rate was lower than the 37% seen in an earlier US phase I/II trial in CTCL. Adverse effects seen most frequently in patients treated with Poteligeo were drug rash and infusion-related reactions, such as chills and flushing, which were said to be manageable and consistent with previous reports.
Poteligeo has a curious history; in 2014 Kyowa struck a deal over it with Pfizer, though this did not extend beyond an agreement to work together on a clinical trial in combination with the US firm’s CD137 MAb PF-05082566 (Ditched marketed drug gets second big pharma endorsement, September 30, 2014).
Back in 2008 Amgen had licensed Western right to the project for non-oncology indications, and had run trials in patients with asthma. However, that deal was canned a couple of years ago.
The Mavoric data could generate partnering interest, and the trial’s inclusion by Ash in the meeting’s press programme will not harm Kyowa’s case either. However, if Poteligeo’s use does not extend beyond CTCL the Japanese group might do just as well to keep global rights to the drug for itself.
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