“WF - SGMO: Hem A Update, Emerging Best-In-Class (Outperform PT 34)
We are reiterating our OUTPERFORM rating on shares of Sangamo
Therapeutics (SGMO) following data update for its hemophilia A gene
therapy, SB-525, with partner Pfizer (PFE). Overall data suggest
stable Factor VIII activity in the normal range between weeks 19-24
for the highest dose cohort and well above the 68% level mean level
from competitor Biomarin (BMRN) at 24 weeks. With Biomarin data
suggesting waning efficacy from 64% to 36% between 12 months
and 24 months, additional follow up will be important but at this
stage data appear best-in-class, in our view, and supportive of
significant upside potential given Pfizer investment in late stage
development and manufacturing.
? Sangamo Therapeutics (SGMO) and partner Pfizer (PFE) reported
over the weekend updated data from the phase 1/2 Alta study of
their gene therapy product candidate SB-525 in hemophilia A at the
International Society on Thrombosis and Haemostasis (ISTH)
meeting, and also announced that FDA has granted SB-525 the
RMAT (regenerative medicine advanced therapy) designation.
? The Alta study treated 10 patients at four dose levels (9E11, 2E12,
1E13, and 3E13 vg/kg). The highest dose cohort has treated 4
patients, including 2 patients (P7 and P8) for whom initial data were
reported in April 2019, and two new patients (P9 and P10). The
factor VIII (FVIII) levels in P7 and P8 remained in normal range
(measured by a chromogenic assay) at 24 and 19 weeks of follow-
up, respectively. The two new patients, P9 and P10, had 6 and 4
weeks of follow-up, respectively, and they demonstrated rapid FVIII
increase kinetics that appear consistent with P7 and P8 at similar
time points (though with slightly lower starting levels). SGMO noted
that, after the data cut-off for the ISTH presentation, P9 reached
normal FVIII levels at week 7. Overall, it was noted that patients in
the highest dose cohort reached normal FVIII levels (50-150%)
within 5-7 weeks of treatment, with sustained FVIII levels and no
bleeding episodes and no factor replacement use. SGMO also
reported that the two patients treated in the second highest dose
cohort (1E13 vg/kg) have demonstrated durability of FVIII levels
through weeks 52 and 32, respectively.
? SB-525 was described as generally well tolerated. Patients in the
Alta study were not treated with prophylactic steroids. There was
one case of treatment-related SAE as previously reported
(hypotension and fever 6 hours after SB-525 infusion), and no
similar hypotension event was observed in the three subsequent
patients dosed. ALT and AST elevation occurred in 30% and 10% of
patients, respectively, though no patients experienced ALT elevation
associated with loss of FVIII expression. In the highest dose cohort,
2 patients experienced Grade 1 ALT elevation (above 1.5x baseline)
managed with a tapering course of oral steroids.
? SGMO expects to treat the 5th patient (P11) in the 3E13 vg/kg dose cohort soon, and SGMO and PFE are working on plans to advance SB-525 to a registrational study. PFE is to assume responsibility for SB-525 late-stage development and manufacturing, and transfer of the SB-525 manufacturing process from SGMO to PFE has been initiated.
? SGMO announced that, based on data from the Alta study, the FDA has granted RMAT designation for SB-525 to treat severe hemophilia A. RMAT designation, granted to regenerative medicine therapies with preliminary clinical evidence indicating the potential to address an unmet medical need with a serious condition, includes all the benefits of fast track and breakthrough therapy designation programs, including early interactions with FDA.”
