Freeline Goes All in on Gaucher Disease


The company’s pipeline is down to 1 remaining clinical-stage program that is enrolling in its first-in-human trial.

Freeline Therapeutics is deprioritizing FLT190, its gene therapy program for Fabry disease in favor of FLT201 for Gaucher disease. The company also announced that it would be cutting 30% of its workforce.1

“While we remain encouraged by the data on FLT190 in Fabry disease, we have paused its development and are further streamlining the organization to extend our cash runway and focus on FLT201 in Gaucher disease,” Michael Parini, chief executive officer, Freeline,said in a statement.1 “I want to extend my sincere gratitude to all of our colleagues for their dedication and their contributions to Freeline, as well as to the investigators and patients who have participated in and supported the development of FLT190.”

FLT190 uses an AAVS3 capsid and is intended to deliver a functional copy of GLA. It is being evaluated in the phase 1/2 MARVEL-1 clinical trial (NCT04040049), which only dosed the first patient in its second cohort in October 2022.2 Early data from the trial has demonstrated a potential dose-dependent increase in α-Gal A levels in the plasma, with 1 of the 2 treated patients having durable α-Gal A levels sustained for up to 2 years. The therapy was well-tolerated, despite a case of transient transaminitis.

“We believe FLT190 has the potential to be a life-changing therapy for people with Fabry disease by providing durable enzyme activity above the normal range with a 1-time treatment, and we are excited to have initiated this cohort in MARVEL-1,” Pamela Foulds, MD, chief medical officer, Freeline said in a statement about the new data.2 “We have multiple trial sites now open across five countries with more expected to open by year-end. We look forward to reporting updated safety and efficacy data in the first half of next year.”

READ MORE: Gaucher Disease HSC Gene Therapy Demonstrates Efficacy and Safety in Phase 1/2 Trial

The announcement comes after a similar update in November 2022, when Freeline announced that it would be deprioritizing its hemophilia B gene therapy program, FLT180a.3 Data from the phase 1/2 B-AMAZE trial (NCT03369444) and its long-term follow-up study (NCT03641703) presented in 2022 showed that 9 out of 10 patients (90%) dosed with FLT180 had sustained FIX activity at a median follow-up of 27.2 (range, 19.1-42.4) months.4 As of the last follow-up, 5 patients (50%) had FIX levels in the normal range (51-78), 3 (30%) had levels ranging from 23-43% of normal. One patient (10%) in the high-dose cohort had 260% normal FIX activity. Mean annualized bleeding rate (ABR) across all patients decreased from 2.93 events per year (range, 0-7.33) at baseline to 0.71 events per year (range, 0-1.7) after treatment and mean annualized FIX consumption per patient decreased from 226,026 IU per year (range, 83,263-423,333) at baseline to 9,723 IU per year (0-95,532).

“The B-AMAZE long-term data continue to support our confidence that a single dose of FLT180a could protect people with hemophilia B from bleeding and the need for lifelong FIX replacement through durable expression of FIX at protective levels,” Foulds said in an earlier statement.4

FLT201 delivers an engineered glucocerebrosidase (GCase) transgene and is set to be evaluated in the phase 1/2 GALILEO-1 clinical trial (NCT05324943) which is currently screening patients with Gaucher disease type 1. Initial data from the first cohort of the trial is expected in the third quarter of 2023.1 FLT201 has so far demonstrated an ability to yield high GCase expression and GCase uptake and clearance of harmful substrates in low doses in preclinical models.

1. Freeline Reports Full Year 2022 Financial Results and Provides Corporate Update. News release. April 4, 2023.
2. Freeline initiates dosing of second cohort in MARVEL-1 trial of FLT190 gene therapy candidate for people with Fabry disease. News release. Freeline Therapeutics Holdings plc. October 4, 2022.
3. Freeline Reports Third Quarter 2022 Financial Results and Corporate Update. News release. Freeline Therapeutics. November 15, 2022.
4. Chowdary P, Shapiro S, Makris M, et al. Phase 1–2 trial of AAVS3 gene therapy in patients with hemophilia B. N Engl J Med. 2022; 387:237-247 doi: 10.1056/NEJMoa2119913
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