Jefferies (schat ONCE hoger/beter/alles in)
uniQure N.V. (QURE): Incremental Update on AMT-060 at WFH; High-Dose Data Expected at ASH
Rating BUY
Price Target $28.00
Price $7.14
Bloomberg NASDAQ: QURE
Key Takeaway
Updated AMT-060 low-dose data for hemophilia B at WFH shows stable/durable FIX activity (mean activity of 5.4% at 26-39wk f/u [n=5]), not compelling vs. ONCE's SPK-9001; awaiting high-dose data at ASH. We view commercial potential for hemophilia B gene therapy as quite low given small pt population (~1/5 of hemophilia A) & convenience of long-acting rhFIX. For hemophilia A, QURE expects to select a lead by YE17, ~1-2 yrs behind BMRN & ONCE.
Updated data for gene therapy AMT-060 in hemophilia B at WFH showed maintained FIX expression of <2.0%-7.2% at 26-39wks f/u (vs. <2.0%-6.9% at 6mo at EHA). Updated low-dose cohort data from Ph1/2 trial of AMT-060 (5x1012 gc/kg; n=5) presented at the World Federation of Hemophilia (WFH) showed FIX expression of <2.0%/2.9%/4.7%/6.6%/7.2% at 26/26/39/39/39 wks; see Chart 1 on pg. 2 for more details. As previously reported, 4/5 pts were able to discontinue prophylactic rFIX; the fifth pt (FIX level <2%) had a trend toward fewer bleeds. Two SAEs have been reported - one pt with a mild, transient, asymptomatic ALT elevation at ~10 wks post-tx which resolved following 8wks of tapering prednisolone doses and the other pt with self-limiting fever in the first 24 hrs after dosing.
Earlier this week, competitor ONCE's hemophilia B gene therapy candidate SPK-9001 showed sustained steady-state FIX levels of ~20%-44% in 4 pts at 12-31wks f/u (vs. ~26%-41% at 7-26wks previously). Spark Therapeutics' (ONCE, Hold)/Pfizer's (PFE, Buy) Ph1 trial of SPK-9001 evaluates a 5x1011 vg/kg dose (~1/10th of AMT-060 low dose). There continues to be no observed elevations in liver enzymes, thus no need for steroids. One FIX concentrate infusion was required for a suspected ankle bleed 2 days post-tx, but otherwise none of the pts received FIX concentrate infusion.
AMT-060 high-dose data on track for ASH on 12/3-12/6/16. All pts have been dosed in the AMT-060 high-dose cohort (2x1013 gc/kg, 4x the low-dose; n=5) as of 5/31/16. However, QURE does not seem to expect ~4x higher FIX levels (vs. low dose). Non-human primate (NHP) data showed dose-dependent increases in FIX levels, but not in a linear manner. Even with potential ~2x increases in FIX levels at the high dose, AMT-060 would still not be as compelling as competitor's data. While FIX levels >5% of normal are clinically meaningful (considered a mild phenotype per International Society on Thrombosis and Haemostasis guidelines), hemophilia experts seem to have a higher bar for gene therapy (e.g., from ~5-25% to up to ~50-60%) given concerns about long-term safety & current availability of effective treatment options.
In hemophilia A, competitive hurdles are also high based on BMRN's Ph1/2 data; QURE to select a lead candidate by YE17 (vs. prior YE16/early-2017).QURE is evaluating candidates in preclinical studies and now expects to identify a lead by YE17. Recall that Ph1/2 data of BioMarin's (BMRN, Buy) gene therapy BMN 270 for hemophilia A showed FVIII expression of over 200% of normal at a dose of 6x1013vg/kg. ONCE is to initiate a Ph1/2 trial of SPK-8011 for hemophilia A in ~2H16 with potential data in 1H17.