- Homology Medicines on Tuesday disclosed the first clinical data for its experimental gene therapy treatment for phenylketonuria, or PKU, announcing interim results from the first three patients treated.
- While too early to conclude much about the treatment's benefit, Homology's readout marks a step forward for clinical research on the rare inherited disorder, a focus for several other drug developers as well.
- The first two participants on a low dose did not see a reduction in an amino acid that builds up in the bodies of those with PKU. A third saw an early but more pronounced effect from treatment. Shares in the biotech fell in post-market trading.
Rare disease drugmaker BioMarin sells two therapies for PKU, a metabolic disease caused by a genetic inability to break down an amino acid found in protein-containing foods and artificial sweeteners.
But, like many inherited diseases with clear genetic roots, the condition is newly a target for gene therapy biotechs like Homology.
Tuesday's update includes data from the first three adults with PKU treated with Homology's gene therapy, known as HMI-102.
Two patients received the lowest dose, while one received a higher dose. Homology is not providing the exact dose levels, citing competitive reasons. A fourth patient received the higher dose after Dec. 2, the cut-off for compiling results, Seymour said.
While the trial will track these patients for one year, this first glimpse included data on only the first few months following treatment of the three patients.
Both trial participants on the low dose did not experience a reduction in phenylalanine, or Phe, the critical amino acid in PKU. Over time, high levels of Phe can lead to intellectual disabilities and brain damage.
Homology is more optimistic about the third patient, who saw a reduction in Phe and a corresponding increase in tyrosine, another amino acid that is typically at lower levels in PKU patients, after receiving the higher dose.
Homology's Phase 1/2 trial is still in initial stages, with the potential to increase dosing in the future. Albert Seymour, the biotech's chief scientific officer, said in a Tuesday interview that decisions on dose escalation are likely to be made when more data is available in a planned mid-2020 update.
Seymour said this small amount of data gives him confidence that HMI-102 successfully delivers the PAH gene into cells. For the two patients on the low dose, the company measured vector copy numbers in the blood, which is evidence the therapy is present, he said.
Reduced Phe and increased tyrosine in the third patient also suggest HMI-102's activity. After four weeks, Phe levels declined by 48% compared to baseline, while tyrosine levels rose by 85%.
By comparison, BioMarin's Palynziq (pegvaliase) showed a roughly 62% reduction in Phe levels among patients treated with a 20 mg once daily dose of the enzyme substitution therapy.
Without data from more patients over a longer time period, Homology's therapy will be hard to assess. Next year could prove critical, though, as BioMarin is preparing to start a Phase 1/2 study of its own PKU gene therapy early in 2020.
Sangamo Therapeutics, meanwhile, announced on Tuesday plans to begin clinical study of a PKU gene therapy in 2021.
"We do feel we are considerably ahead of all the competition in the gene therapy space," Seymour said, referring to the PKU work from BioMarin and Sangamo.
Other approaches are getting attention, too. Rubius Therapeutics, Synlogic and Codexis have PKU therapies in clinical testing, while Moderna and Agios Pharmaceuticals have both said they are doing preclinical research on the disorder.