With a new No. 1, Avrobio hopes to get investors back on gene therapy bandwagon

It’s been a year since Avrobio suffered a blow to its gene therapy ambitions with the failure of a Fabry disease program. Now, the biotech is ready to reintroduce itself to investors with a small positive data set for its new No. 1 priority and the go-ahead from the FDA to advance the clinical program in a rare disease.

Avrobio will preview its new course Wednesday morning, showcasing data from five patients with Gaucher disease two years after receiving the gene therapy AVR-RD-02 in the phase 1/2 Guard1 trial. It’s a small interim data set, but, for the first time, Avrobio is presenting evidence of improvement in a patient with the more severe type 3 form of the disease.

The five patients, four with type 1 and one pediatric case with type 3, saw stabilization of multiple clinically relevant measures for the lysosomal disorder. For the type 3 patient, Avrobio said the data show a complete biochemical correction, meaning both enzyme activity and substrate levels normalized after treatment with AVR-RD-02.

Avrobio found sustained engraftment, which is a sign of the gene therapy taking in a patient, at 14 weeks and two years post treatment.  

Gaucher disease is characterized by the accumulation of fatty substances in the body, which can lead to a grossly enlarged spleen and liver. It’s typically treated with enzyme replacement therapy, but patients still have a shortened life span and experience debilitating symptoms, according to Avrobio. Type 3 is more severe and progressive, tends to be resistant to treatment and comes with neurological symptoms.

The small data set was enough to convince U.S. and U.K. regulators that it’s time for a phase 2/3. Avrobio met with the FDA and the U.K. Medicines and Healthcare products Regulatory Agency recently and was given the okay to advance the trial for AVR-RD-02 in the more severe Gaucher subtype.

The company expects to get this off the ground in the second half of 2023 with about 40 patients who will be randomized to receive standard of care or the gene therapy. The main goal will be measures of impaired coordination, breathing ability and liver and spleen volume, while a secondary goal will look at substrate levels in the cerebrospinal fluid to determine the gene therapy’s impact in the central nervous system.

All this news could help bring investors back online after Avrobio was forced to ax a Fabry disease therapy last year due to lackluster data. Mizuho Securities said in a Dec. 5 note before the data were issued that the Gaucher update, if positive, will help “reinvigorate interest in the stock.” The Gaucher program has become Avrobio’s new No. 1 priority, according to the analyst firm.

The new data are the first to highlight Avrobio’s plato gene therapy vector again since the Fabry flop, so investors will be eyeing the engraftment data closely, Mizuho said. Since the Fabry data were variable on engraftment, investors were worried that the entire gene therapy program might be problematic. Strong engraftment data “could help to restore faith in the company's platform,” according to Mizuho.

One piece that may be missing is later-stage advancement on type 1. Mizuho said investors would be closely watching for clinical advancement for both types. Avrobio only had news to share about type 3 in the Wednesday morning release. The type 1 indication would represent a “multi-billion dollar sales opportunity,” according to Mizuho, while type 3 would be a much smaller patient population.

While the phase 2/3 gets underway in type 3, Avrobio will continue enrolling the phase 1/2 for type 1 patients, a spokesperson confirmed to Fierce Biotech. So far, four patients have been dosed and six are enrolled, with space for up to 16 patients.

If Avrobio were to get the Gaucher disease gene therapy onto the market, Mizuho said it would be a first. While ERT is the standard of care for type 1 patients, no treatments are approved specifically for the more severe type 3, meaning the company would be addressing a high unmet need.

The total patient population is about 20,000 globally, of which 5% are type 3, according to Mizuho. About half of type 1 patients are well controlled on ERT, meaning the addressable population that may consider gene therapy is about 8,000.

Competitors in the space include Eli Lilly and Prevail Therapeutics, and Freeline Therapeutics, but Avrobio is the only gene therapy candidate “in the horizon,” Mizuho said.

Mizuho estimates that the wholesale acquisition cost for AVR-RD-02 would be $2.3 million, which is about five years’ worth of ERT. That means Avrobio would not need a huge market share to generate billions in sales, according to the analysts.

Avrobio will host an update on the Gaucher program Wednesday at 8 a.m. ET. The company's shares were trading up just under 6% in pre-market trading to 89 cents, compared to a prior close of 84 cents.