Amicus muscles in on Pompe gene therapy chase

As data on Amicus Therapeutics' clinical-stage Pompe disease candidate roll in, the group locks up preclinical gene therapy assets.

Credit Amicus Therapeutics for realising that next-generation enzyme-replacement therapy might soon be eclipsed by a new technology. A gene therapy deal with – who else? – the University of Pennsylvania for projects that could make Galafold and ATT-GAA obsolete in a few years could help keep the company on even terms with rivals like Avrobio and Spark Therapeutics.

The deal will do little to tamp down gene therapy investors' sky-high expectations, as even early-stage developers like Audentes and Crispr Therapeutics carry valuations above $1bn. In a few short weeks Amicus has become one of the bigger players in gene therapy, at least at the preclinical level, having done a similar deal with a spinout of Nationwide Children’s Hospital last month.

Yesterday, Amicus licensed assets aimed at Fabry and Pompe diseases, CDKL5 deficiency and an unnamed metabolic disorder, emerging from Dr James Wilson’s laboratories at the University of Pennsylvania. No terms were disclosed. Last month, Amicus paid $100m up front to buy a gene therapy spinout of Nationwide called Celenex for access to 10 projects in lysosomal storage disorders such as Batten disease (Gene therapy deal-making shows no signs of stopping, September 24, 2018).

The latest deal came in spite of the launch of the Fabry disease drug Galafold in the US and progress for ATT-GAA in Pompe disease; however, Amicus has previously said that, although these agents were a step forward from the current standard of care, it was determined to find a cure for these disorders.

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While an accelerated approval for ATT-GAA on phase II data looks in doubt, the New Jersey-based company last week released updated results from that trial at the World Muscle Society meeting in Mendoza, Argentina, through 18 months.

The long-term data came in 20 patients; 11 of these were ambulatory and switched from enzyme-replacement therapy (ERT), four were non-ambulatory ERT switch patients, and five were ambulatory subjects who had never taken ERT. One of the first cohort dropped out of the trial because of the travel burden.

Of note, the six-minute walk test for the ambulatory patients at 18 months increased for all but one, with one of the 10 remaining switching patients not having had a clinic visit at the time of the data cut.

Body strength endpoints trended positively, along with fatigue scores. Lung function tests were a little more mixed, with ambulatory switch patients’ forced vital capacity stabilising but not improving.

Amicus has added another cohort to the ATB200-02 trial, which will include up to 10 more ERT switch patients; the group hopes that these data, along with results from a natural history study, will be enough for a second attempt at accelerated approval. However, it might need to await the outcomes of a 100-patient phase III trial, due to start this year.

The launch of Galafold and, potentially, AT-GAA would be good news for just about any company, but Amicus seems to be aware that the competitive landscape could quickly shift against its agents, which correct faulty enzymes but require frequent dosing – intravenous infusions in the case of AT-GAA.

The state of competition was made clear in the week leading up to World Muscle, when Avrobio reported phase I data with its gene therapy candidate AVR-RD-01 in Fabry disease. This was seen by investors as disappointing, and Avrobio shares fell 52%.

Gene therapy in lysosomal storage disorders
  Project Company Phase
Pompe disease AAV2/8-LSPhGAA Actus Therapeutics Phase I
  SPK-3006 Spark Therapeutics Preclinical
  AT982 Audentes Preclinical
  AVR-RD-03 Avrobio Preclinical
Fabry disease AVR-RD-01 Avrobio Phase II
  ST-920 Sangamo Preclinical
Source: EvaluatePharma.

Amicus's chief executive, John Crowley, recently told Vantage that his company had an obligation to patients to "obsolete" its own technologies (Amicus’s Pompe disease setback doesn’t dent gene therapy enthusiasm, September 10, 2018).

If the group wants to persist in these rare diseases, advancing a gene therapy is certainly a competitive reality, and Mr Crowlely's team seems to be making an effort to rise to this challenge. Sangamo is also queuing up a gene-editing approach in Fabry disease, with ST-920. In Pompe disease, the competition looks even more keen, with Spark, Avrobio, Audentes and Actus Therapeutics all active.

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