Upcoming events: Sirukumab and serelaxin face phase III readouts

Welcome to your weekly digest of approaching regulatory and clinical readouts. GlaxoSmithKline and Johnson & Johnson will soon report the first phase III results with their rheumatoid arthritis (RA) hopeful sirukumab, while Novartis is getting another shot with its heart failure candidate serelaxin.

Sirukumab has promise as a best-in-class IL-6 MAb if phase II results are anything to go by. Meanwhile, the recombinant hormone serelaxin looks likely to have a tougher time of it in the Relax-AHF2 study, which became the main focus after an FDA advisory panel knocked it back last year.

Sirround sound

The first phase III study of sirukumab to read out should be Sirround-H, which is comparing the project against Humira. The primary endpoints are change from baseline in the DAS28 score and the percentage of patients with an ACR50 response – a 50% improvement in RA signs and symptoms.

Results from Sirround-T are due not long after. This study is comparing sirukumab with placebo in patients who do not respond to or are intolerant of anti-TNF therapy and has a primary endpoint of ACR20, the proportion of patients with a 20% improvement in disease.

If it comes close to the 83% ACR20 rate seen in phase IIb approval should be a given – and will make sirukumab a formidable competitor to Roche’s Actemra, the only anti-IL-6 approved for RA. Actemra’s label cites ACR20 responses across five trials of between 48% and 70%.

But sirukumab will not have long to establish itself before RA biosimilar competition kicks in – Actemra is due to come off patent in 2019, while AbbVie’s anti-TNF agent Humira is facing expiry in December 2016.

Another potential rival is Sanofi’s sarilumab, which should beat sirukumab to the market with a US filing expected before the end of the year. However, when it comes to efficacy sarilumab has disappointed in pivotal trials, with an ACR20 of only 56-61% (Why Sanofi’s arthritis biologicals lead could be short-lived, May 21, 2015). 

Therefore if sirukumab can outdo sarilumab in phase III there might be an upgrade to the former’s 2020 consensus sales forecast, which currently stands at $461m. Any improved performance might come from the fact that Actemra and sarilumab target the IL-6 receptor, while sirukumab targets the IL-6 cytokine itself.

As well as the aforementioned pivotal trials, sirukumab is also being studied in Sirround-D in patients who have failed on DMARDs, and Sirround-LTE, a long-term trial.

Second shot for serelaxin

Serelaxin was once one of Novartis’s big heart failure hopes but it has been eclipsed by Entresto, which was approved this year.

The company is ploughing on with serelaxin in spite of a mixed bag of results from the previous phase III Relax-AHF study – which intriguingly found a 37% reduction in cardiovascular death, albeit it in a retrospective analysis (Serelaxin data judged incomplete as FDA panel sends it back, March 28, 2014). 

While the ongoing Relax-AHF2 trial is not due to report until 2016, interim results are expected by the end of this year. But analysts are not getting too excited, and some doubt that it can meet its primary endpoint of time to cardiovascular death during the 180-day follow-up period.

Bank of America Merrill Lynch and Leerink both believe that interim success is unlikely, but the former expects a positive result when full data are reported towards the end of 2016. Leerink, on the other hand, is becoming increasingly sceptical about the final read-out “given management’s lack of conviction” at a recent analyst event.

If interim results are unexpectedly positive approval should be relatively straightforward, given that serelaxin already has breakthrough therapy designation.

But even if Novartis has to wait another year this would not be the end of the world if this still meant eventual approval of a drug with peak sales of $1.8bn, as the Bank of America Merrill Lynch analysts forecast.

This is small fry compared with Entresto, which is expected to bring in $5.4bn in 2020, according to EvaluatePharma consensus. But after spending so much time and money on serelaxin, Novartis will not want another setback.

To contact the writer of this story email Madeleine Armstrong in London at [email protected] or follow  @medtech_ma on Twitter