WFH 2018 – Spark keeps its haemophilia B gene therapy edge, for now

Spark Therapeutics already looked to have the advantage over its rival Uniqure in the battle of the haemophilia B gene therapy projects. Data presented at the World Federation of Hemophilia meeting in Glasgow, UK, have done nothing to change the status quo – but Spark might not be in the driving seat for much longer.

Uniqure has a trick up its sleeve. It plans to start a phase III trial this year with AMT-061, a new candidate using the Padua factor IX variant – this is already employed by Spark’s SPK-9001 and might account for that project’s higher FIX activity versus Uniqure’s older contender, AMT-060. With Spark’s partner Pfizer taking over the reins for phase III, the fight over the haemophilia B gene therapy space can only intensify.

Padua patent?

It is unclear whether skirmishes could yet break out over intellectual property. Uniqure said last year that it had acquired a patent family broadly covering the Padua variant from its inventor, Professor Paolo Simioni, who is now serving as an advisor to the company.

“Regarding the IP, we hold a very strong position,” a Uniqure spokesperson told EP Vantage today.

But Katherine High, head of R&D at Spark, seemed sceptical, telling EP Vantage that “several different groups have claimed IP for the Padua variant”, including Baxalta for the now-abandoned BAX 335.

She went on to question whether any such patents would be valid: “The Padua variant was described as a naturally occurring variant. So I guess the question is whether that can be protected and, if so, whose patent is dominant? The IP situation is somewhat confused.”

Ms High declined to say whether Spark held patents covering the variant, but this now appears to be Pfizer’s problem. “We’ll have to rely on our colleagues at Pfizer to sort that out with the other players in the field.”

As for how Uniqure is able to take AMT-061 straight into phase III based on phase I/II data with AMT-060, the company said the FDA and EMA had agreed to this because of similarities between the two molecules. “AMT-061 and AMT-060 are identical in structure apart from two nucleotide substitutions in the coding sequence for FIX,” the spokesperson said.

Spark’ll FIX it

Based on the data available so far, Uniqure has a way to go to catch up with Spark.

SPK-9001’s ongoing phase I/II trial previously found mean FIX activity of 34% in the first 10 patients treated with SPK-9001; these data were published in the New England Journal of Medicine in December. This compares with mean FIX activity of 4.8% and 7.2%, in the low and high-dose cohort respectively, from the most recent analysis of AMT-060’s phase I/II study.

The new development for Spark, presented at the WFH congress today, involved data from four patients receiving SPK-9001 manufactured using an “enhanced” process that is more easily scalable and could be suitable for commercialisation, Ms High explained.

The results appear to show comparable outcomes based on FIX activity. Spark noted that in the three patients treated with SPK-9001 produced using this process, and who reached 12 weeks' follow-up or more, steady-state FIX activity levels were 38-55%.

However, these numbers should be approached with caution, as only one of the patients has been followed for a year, and the remaining data are relatively early.

Spark plans to complete the transfer of SPK-9001 to Pfizer this summer, and the bigger company will then take SPK-9001 into phase III. Details about the trial are scant, but it seems likely that Pfizer would want to use the enhanced manufacturing process.

As for when phase III might begin, this could be on the cards by the end of 2018, Spark’s Ms High said: “We’ve manufactured a lot of vector for them, which we expect to deliver in the third quarter of this year. I would assume that means it won’t be too much longer until they [start].”

While Spark seems to be winning the haemophilia B gene therapy battle for now, Uniqure will be hoping to turn the tables in phase III. Data – as well as hints about how any patent tussle might turn out – will be needed to crown the eventual winner.

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