Gene therapy results look less than Solid

Solid Biosciences’ muscular dystrophy gene therapy fails to hit the company’s own target, let alone a benchmark set by Sarepta.

For Solid Biosciences the good news today was that there was no repeat of a toxicity problem with SGT-001 that had triggered last year’s clinical hold and threatened to scupper the group’s Nasdaq flotation. And that was more or less where it ended.

The keenly awaited first results from a phase I Duchenne muscular dystrophy trial have shown vanishingly small evidence of activity backing SGT-001, the group’s gene therapy, sending shares crashing 70% while its rival Sarepta climbed 7%. Solid has now put its faith in higher dosing – something it assures investors it can do “without delay”.

For now, however, the markets have little hope to cling to. In just one patient given SGT-001, a gene therapy coding for microdystrophin, detectable microdystrophin levels were below 5% when using Western blot analysis, or 10% using immunofluorescence.

Analysis of this trial, known as ignite-DMD, related to the first three subjects dosed, another three having received placebo control and able to switch to the active cohort after 12 months. Unfortunately for Solid, the other two active arm subjects had undetectable microdystrophin via Western blot, and “very low levels” by immunofluorescence.

At last month’s JP Morgan conference Solid had set 10% expression levels as a minimum for SGT-001 (Solid guns for Sarepta, January 22, 2019). Even worse, Sarepta’s competing gene therapy, rAAVrh74.MHCK7.micro-dystrophin, triggered microdystrophin expression of 74-96% in the first three children dosed, though these measurements were taken using different methods.

Not apples to apples

There are other reasons why the read-across between the competing gene therapies is not straightforward. For one thing Sarepta’s trial enrols children, while Solid’s is recruiting ambulatory children and non-ambulatory adolescents, who are clearly in a more advanced state of DMD.

Equally importantly, the Ignite-DMD data relate only to SGT-001’s lowest dose, 5x1013vg/kg. rAAVrh74.MHCK7.micro-dystrophin has been dosed severalfold higher, at 2x1014vg/kg.

Sure enough, while Solid’s JP Morgan pitch played up the 10% bar for efficacy, today the group’s attention switched to how much scope there still was in Ignite-DMD to dose-escalate and thus, presumably, to elicit higher microdystrophin expression. On an analyst call the company said the next subject would be dosed higher; it had previously planned to start dose escalation from patient five.

Still, even if Solid can immediately dose-escalate, whether it can do so safely could continue to trouble investors. Last year’s clinical hold concerned decreased platelet count and evidence of complement activation in the first subject given 5x1013vg/kg, and at one point Solid was forbidden from dosing any higher.

As such, investors must now hope that Solid’s plan to manage the toxicity with steroids and Alexion’s Soliris is effective. The group today insisted that SGT-001’s safety profile was unchanged. It also said it had $145m in the bank, a sum that should sustain it until the end of the first quarter of 2020.

This is at least something, as the company’s chances of raising cash at this morning’s collapsed valuation are negligible.

Share This Article