New data Spark haemophilia B gene therapy battle

UniQure’s haemophilia B gene therapy candidate AMT-060 was already looking second-best compared with Spark Therapeutics’ rival project SPK-9001. New data have done nothing to close the gap – if anything, they have made it wider.

UniQure and Spark are both near the front of the race to develop a haemophilia B cure, one of gene therapy’s most active areas (see tables below). But while the companies could steal a march on Baxalta’s BAX 335, development of which seems to have stalled with Shire’s takeover, at the moment Spark looks like the one to beat.

FIX it

Broadly positive data from a phase I/II study were not enough to save UniQure’s stock, which dropped 16% on June 13, the first trading day after its presentation at the European Hematology Association meeting. The group’s share price is down 41% from the beginning of the year.

While AMT-060 was on the face of it a success – four out of the five treated patients did not require prophylactic factor IX (FIX) infusions, and all of them ended up with less severe disease than at baseline – it fell short on the amount of FIX activity, which should correlate with blood-clotting ability.

Before treatment At six months post AMT-060
Patient FIX activity Haemophilia phenotype Prophylactic FIX infusions? FIX activity Haemophilia phenotype Prophylactic FIX infusions?
1 <1% Severe Yes 6.3% Mild No
2 <1% Severe Yes 5.4% Mild No
3 <1% Severe Yes <2.0% Moderate Yes
4 1.5% Moderate-severe Yes 6.2% Mild No
5 <1% Severe Yes 2.9% Moderate No

Spark’s SPK-9001, meanwhile, had a much more impressive 27-35% range of FIX activity in four patients in its phase I/II study – even better than the 16-30% that the company had previously disclosed (EHA preview – First blood for Spark, May 20, 2016).

UniQure will hope for more convincing results from the high-dose cohort of the same trial, which is expected to report initial data by the end of 2016.

This is not a given, however. Spark’s therapy is administered at a lower dose than UniQure’s, but seems to lead to a stronger response. The answer could lie in Spark’s approach – while UniQure’s product encodes wild-type FIX, Spark’s employs a mutated version called Padua FIX. The Padua variant is thought to result in higher FIX activity and therefore improved blood clotting.

Spark’s success could therefore be a negative not only for UniQure but also for other groups developing wild-type products, including Dimension Therapeutics.

But caution is needed with such small patient numbers, and FIX activity might not be the be-all and end-all – it is thought that only around 5-10% activity is required to spur a therapeutic effect.

Even so, Spark seems to have the advantage for now. If it can replicate its impressive results in phase III in more patients its product could become the haemophilia B gene therapy of choice.

Haemophilia B gene therapy pipeline
Company Project Mechanism Notes Trial details
Baxalta (Shire) BAX 335 AAV8-Padua FIX Phase III to start 2016 NCT01687608
UniQure/Chiesi AMT-060 AAV5-wild-type FIX Low-dose phase I/II data presented at EHA; high-dose data H2 2016 NCT02396342
Spark/Pfizer SPK-9001 Bio-engineered AAV-Padua FIX Low-dose phase I/II data presented at EHA NCT02484092
Dimension Therapeutics/ Regenxbio DTX101 AAVrh10-wild-type FIX Initial phase I/II data due H2 2016 NCT02618915
Sangamo Biosciences SB-FIX In vivo protein replacement using zinc finger nucleases Phase I trial started in 2016 NCT02695160
Freeline Therapeutics Haemophilia B Gene Therapy Self-complementary AAV8 FIX Claims to have been studied in human trials Unknown

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

Share This Article