RA setbacks for AstraZeneca and Lilly
pharmafile | December 14, 2012 | News story | Research and Development, Sales and Marketing | AstraZeneca, Humira, RA, lilly
AstraZeneca and Eli Lilly have both suffered setbacks in their attempts to push their respective investigational rheumatoid arthritis (RA) treatments forward.
AstraZeneca’s oral drug fostamatinib failed to prove non-inferority in its Phase IIb trial against Abbott’s Humira (adalimumab).
Meanwhile Lilly has decided to stop one of its three Phase III studies of tabalumab, an anti-BAFF monoclonal antibody, in RA as it is not effective enough.
Fostamatinib, the first oral SYK (spleen tyrosine kinase) inhibitor in development as a novel therapeutic approach for RA, is thought to reversibly block signalling in multiple cell types involved in inflammation and tissue degradation in the disease.
But AstraZeneca’s OSKIRA-4 study did not meet its second primary objective because all fostamatinib monotherapy doses were inferior to Humira monotherapy at 24 weeks.
The investigators based that disappointing outcome on the drugs’ DAS28 score, a composite endpoint assessing signs and symptoms of RA.
This is important because it was hoped that fostamatinib, which performed solidly in Phase II, would challenge current blockbusters Humira, Pfizer’s Enbrel and Janssen’s Remicade, all of which are injections or infusions.
The six-month OSKIRA-4 study looked at 280 patients with RA who had either never had a disease-modifying anti-rheumatic drug (DMARD), were intolerant to them or had had an inadequate response to DMARDs.
Fostamatinib did meet its first objective – a statistically significant superior DAS28 score change from baseline compared to placebo at six weeks at 100mg twice-daily and 100mg twice-daily for a month, followed by a 150mg once-daily dose.
But the drug did not achieve this at the 100mg twice-daily dose for a month followed by 100mg once a day.
AstraZeneca licensed fostamatinib from San Francisco-based clinical stage drug development company Rigel in 2010 for an upfront payment of $100 million.
The idea had been to file the drug for approval by US and European regulators in 2013, but the latest results would seem to have raised at least a question mark over its progress.
However, AstraZeneca is bullish about filing in the second half of next year: it is not giving up with fostamatinib, and will push on with the Phase III part of OSKIRA, which is looking at the drug in combination with a DMARD.
Martin Mackay, president of AstraZeneca R&D, said this was “on track to report in the first half of 2013, and would form the basis of regulatory submissions”.
This is a competitive marketplace, with Pfizer’s investigational RA pill tofacitinib, a first-in-class Janus kinase (JAK) inhibitor, also in the mix.
Lilly will incur a fourth-quarter charge of up to $35 million for stopping the FLEX-M study – but insists the decision to abandon it was not down to safety concerns.
Tabalumab (LY2127399) is being investigated for the treatment of patients with moderate-to-severe RA who had an inadequate response to methotrexate therapy.
“The results of this study were unexpected given the data generated in earlier Phase II clinical studies of tabalumab,” admitted Eiry Roberts, vice president of autoimmune product development at Lilly.
The manufacturer is carrying on with tabalumab in two other Phase III RA registration studies as well as an open-label extension study and several smaller studies.
Adam Hill
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