Eli Lilly discontinues Gaucher type 1 gene therapy trial from Prevail buyout

USA—Eli Lilly has discontinued another clinical trial involving a gene therapy it acquired through its US$1 billion purchase of Prevail Therapeutics, further shrinking the assets it inherited from the biotech.

Lilly disclosed the decision as part of its second-quarter results, removing a phase 1/2 study of LY3884961 in Gaucher disease type 1 (GD1) from its pipeline.

The move leaves the company pursuing the GBA1 gene therapy only in Parkinson’s disease.

Prevail had two leading gene therapy programmes when Lilly agreed to acquire the biotech for US$ 1 billion in late 2020.

However, Lilly discontinued the frontotemporal dementia candidate LY3884963 in February, making LY3884961 its remaining lead asset from the acquisition.

Lilly narrows Gaucher gene therapy programme

The discontinued GD1 study was designed to assess the safety and tolerability of up to three doses of LY3884961 in approximately 15 adults with peripheral manifestations of the inherited lysosomal storage disorder.

Gaucher disease type 1 results from mutations in the GBA1 gene that reduce the activity of an enzyme required to break down certain fatty substances in cells.

Gene therapy developers are investigating whether replacing or modifying the defective gene can address the underlying cause of the disease rather than treating its symptoms.

A Lilly spokesperson told Fierce Pharma that the GD1 programme “did not meet our high internal bar for success” and was therefore removed from the pipeline.

The company said it had observed no safety signal and would continue developing LY3884961 for Parkinson’s disease through the Propel trial.

The decision follows several setbacks for the gene therapy since Lilly acquired Prevail.

In the third quarter of 2022, Lilly recorded a US$206.5 million charge, primarily reflecting changes to the estimated launch timing of the therapy.

Then, in the first quarter of 2024, Lilly ended development of LY3884961 in Gaucher disease type 2 (GD2), another form of the disorder.

With the latest decision, the company has now abandoned development of the asset in both GD1 and GD2.

Lilly retains a small gene therapy pipeline

Despite the setbacks, Lilly continues to advance several genetic medicine programmes.

In addition to the Parkinson’s disease programme, the company is conducting phase 1/2 trials of gene therapies targeting otoferlin gene-mediated hearing loss and vestibular schwannoma, a tumour that develops on the nerve responsible for balance and hearing.

Lilly acquired both hearing-related programmes through its US$487million  acquisition of Akouos in 2022.

The withdrawal of LY3884961 from GD1 also changes the competitive landscape for gene therapies targeting the disease.

Spur Therapeutics, formed through the merger of Freeline Therapeutics and SwanBio, is conducting a phase 3 trial of its GBA1 gene therapy in GD1.

Meanwhile, Lingyi Biotech is enrolling patients in a phase 1/2 study of its own candidate, while researchers at Sanofi published findings on their lead GD1 gene therapy candidate, SS3-GBA1, late last year.