Sangamo’s stock price Soars 52% in pre-market hours on hemophilia A trial results

Sangamo’s Stock Price Soars

Sangamo Therapeutics’ (SGMO) stock soared more than 52% in pre-market trading following the announcement with Pfizer (PFE), of interim data from Phase 1/2 Alta study evaluating the firm’s gene therapy product SB-525 for severe hemophilia A. 

The Product, SB-525

SB-525 comprises a recombinant adeno-associated virus serotype 6 vector (AAV6) encoding the complementary deoxyribonucleic acid for B domain deleted human FVIII. The SB-525 vector cassette was designed to optimize both the vector manufacturing yield and liver-specific FVIII protein expression. The SB-525 transcriptional cassette incorporates multi-factorial modifications to the liver-specific promoter module, FVIII transgene, synthetic polyadenylation signal and vector backbone sequence.

Longer-term follow-up data will be presented at an upcoming scientific meeting. Per the SMC recommendation and study protocol, the fourth cohort will be expanded by up to five patients. Patient enrollment is underway.

Data & Statistics for SB-525

Data indicate that SB-525 was generally well-tolerated and demonstrated a dose-dependent increase in Factor VIII (FVIII) levels across the four dosage cohorts. Based on the positive results the Safety Monitoring Committee (SMC) recommended cohort expansion at a higher dose.

According to Edward Conner, MD, Chief Medical Officer of Sangamo, the interim data from the first eight patients with hemophilia A who are treated with SB-525 gene therapy in the Alta study are encouraging and demonstrate: a dose-dependent relationship, evidence of sustained factor levels and low variability, both within each patient and within each cohort. Dr. Conner added, “These interim results suggest that SB-525 may be well-tolerated and may prove to have the predictability and sustained treatment effect that can bring clinical benefit in patients with hemophilia A. We need to continue observing how the data mature and how additional patients in the expansion cohort respond to SB-525. We look forward to working with Pfizer to potentially advance SB-525 into a registrational study.”

The Phase 1/2 interim data patients demonstrated a dose-dependent increase in FVIII levels. The increase in FVIII is clinically relevant.  

At week 6, post infusion, the two fourth dose cohort patients reached 140% and 94% of normal (as measured by one-stage clotting assay) and 93% and 65% (as measured by chromogenic assay, normal range is 50%-150%).

 A dose-dependent reduction in the use of Factor VIII replacement therapy was also observed. Patients  in the highest dose cohort did not require replacement therapy after initial use of prophylactic factor and experiencing no bleeding events to date.

SB-525 was generally well-tolerated with one patient (treated with the 3e13 vg/kg dose) reporting a treatment-related serious adverse event of hypotension and fever, which occurred following vector infusion and resolved with treatment within 24 hours of completion of vector infusion.

Patients in the Alta study were not treated with prophylactic steroids. No treatment-related serious adverse events and no alanine transaminase (ALT) elevations requiring more than seven days of corticosteroid treatment were observed in the first three cohorts.

One patient in the fourth cohort experienced an ALT elevation (>1.5x ULN) at week four that required a tapering course of oral steroids. The patient did not have any associated loss of Factor VIII activity or ALT elevations seven weeks following initiation of the steroid therapy (five weeks post vector infusion). The same patient in the fourth cohort experienced the aforementioned serious adverse event.

A Word from a Study Ivestigator

Barbara Konkle, MD, Bloodworks Northwest and Professor of Medicine at University of Washington and investigator of the Alta study, said, “The interim results with SB-525 gene therapy for patients with severe hemophilia A are early but very promising. It will be important to observe additional patients and for a longer follow-up duration to determine whether these positive interim findings are recapitulated and sustained.”

The Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 in up to 20 adult patients with severe hemophilia A. The U.S. Food and Drug Administration has granted Orphan Drug and Fast Track designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

Sangamo/Pfizer Collaboration

In addition to the partnership for the development and commercialization of gene therapies for hemophilia A, Sangamo and Pfizer are also collaborating on the development of gene therapies for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) using Sangamo’s proprietary zinc finger protein transcription-factor technology.

Prohost Observations

Sangamo’s news is promising and encouraging. It is about a gene therapy with improved Adeno-associated viral vector coming out of a gene-editing firm whose problem was that it took a long time to reach its goals. Recently; however, many emerging signs began to demonstrate that the firm is on its way to bringing to the clinic potent, safe and effective products which act at the root-cause of diseases, i.e., the genes.   

More news has been announced today in addition to a conference call that we will be evaluating and maybe publishing in the Prohost Letter or in separate articles. Regarding the long time taken by Sangamo to realize its goals we remind that many top-tier biotech firms, generating billions of dollars, have taken a long time before their products reach the clinic. One of them is Regeneron, which is currently considered one of the most successful large biotech firms.

We are Happy to hear the good news from Sangamo and continue to believe in it since we added it to the Prohost Portfolio way back in 2011.

Indeed, it is encouraging news.

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