New Data Spark Hemophilia B Gene Therapy Battle

| About: uniQure N.V. (QURE)
This article is now exclusive for PRO subscribers.

UniQure’s hemophilia B gene therapy candidate AMT-060 was already looking second-best compared with Spark Therapeutics’ (NASDAQ:ONCE) 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 hemophilia 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

hemophilia phenotype

Prophylactic FIX infusions?

FIX activity

hemophilia 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 hemophilia B gene therapy of choice.

hemophilia 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

hemophilia B Gene Therapy

Self-complementary AAV8 FIX

Claims to have been studied in human trials

Unknown