The rheumatoid arthritis field is gearing up for a showdown between two new IL-6-targeting MAbs. Johnson & Johnson and GlaxoSmithKline had hoped to position their contender sirukumab as the best-in-class agent to make up for the fact it will reach the market behind another promising new contender – but this now looks in doubt with new data.
The results from the phase III Sirround-D study, being presented at the Eular meeting in London this week, should be enough for approval – but they fall well short of the impressive efficacy seen in phase II. The scene is set for a fierce battle against Sanofi and Regeneron’s rival agent sarilumab.
J&J and Glaxo are expected to file sirukumab in the third quarter of 2016, but sarilumab could be approved soon after – the Sanofi project has a PDUFA date of October 28.
As well as its head start, sarilumab has another advantage, having outperformed the RA stalwart Humira in a head-to-head trial earlier this year (Sanofi’s sarilumab bests Humira to set up arthritis showdown, 11 March 2016).
Sirukumab is also being tested against Humira in the Sirround-H trial, due to complete in September. EvaluatePharma's sellside consensus pegs sirukumab as the bigger seller, with 2022 revenues of $949m versus $753m for sarilumab – but this could change if the J&J/Glaxo asset does not better AbbVie’s bestseller.
In the meantime, Sirroud-D, which tested sirukumab in 1,670 patients who had failed on DMARDs, was far from a disaster. It met its co-primary endpoints of ACR20 response – a 20% improvement in RA signs and symptoms – and joint damage measured using the van der Heijde-Sharp score. Higher scores on the latter measure indicate greater structural damage.
The study also met all of its secondary endpoints with both sirukumab doses. Major clinical response was defined as the percentage of patients achieving ACR70 for six consecutive months.
|Endpoint||Sirukumab 50mg every 4 weeks||Sirukumab 100mg every 2 weeks||Placebo|
|ACR20 at week 16||54.8%||53.5%||26.4%|
|Change in van der Heijde-Sharp score at 52 weeks||0.50||0.46||3.69|
|HAQ-DI score at week 24||-0.43||-0.46||-0.22|
|ACR50 at week 24||30.2%||33.2%||12.4%|
|DAS28 remission at week 24||26.0%||25.5%||5.6%|
|Major clinical response at week 52||5.4%||9.0%||1.8%|
|Note: *all p<0.001 vs placebo.|
Though decent, the latest results are disappointing after the 83% ACR20 response seen in a phase IIb study of sirukumab. They also fall short of the 56-61% that rival sarilumab reported from the Saril-RA-Target study in November; and the 72% ACR20 response in sarilumab’s trial against Humira.
The usual caveats about across-trial comparisons apply, but J&J/Glaxo’s agent is starting to look mediocre. The companies have already said that the Sirround-H and Sirround-T phase III trials met their primary endpoints, but full data will be eagerly awaited for clues on how the battle will play out.
In the end, J&J and Glaxo might be forced to compete on price – which would be good news for payers, but not so much for the companies.
The first paragraph of this article has been amended to clarify that there are other IL-6 drugs on the market already.