The race to treat Duchenne muscular dystrophy with gene therapy, a one-time, potentially long-lasting treatment, is being closely watched. But new data from Solid Biosciences cast doubt on whether the Cambridge, MA, company can keep pace with the current leader, Sarepta Therapeutics.
Solid (NASDAQ: SLDB) this morning is disclosing the first results from the first three Duchenne patients in a study known as IGNITE DMD, an early-stage trial testing its experimental gene therapy, SGT-001. To be clear, the results are early—from biopsies taken three months after treatment—and at just the lowest dose of the gene therapy Solid plans to test.
But the results have fallen short of expectations. Solid says just one of the three patients treated so far has produced detectable levels of micro-dystrophin—a smaller version of dystrophin, the muscle-protecting protein that Duchenne patients lack. And that patient produced less than 5 percent of normal levels of micro-dystrophin, Solid said in a statement.
The results “are lower than what we had hoped based on our preclinical research, but we are confident that we will see higher expression at higher doses,” a company spokesperson told Xconomy. Still, the company is encouraged to see “signals of micro-dystrophin expression” at its lowest dose.
Solid shares plummeted 65 percent, to $7.42 apiece, in midday trading on Thursday.
To put the numbers in context, last week Leerink analyst Joseph Schwartz, in a research note, wrote that micro-dystrophin expression levels lower than 10 percent after three months would be a disappointment. In June 2018, Sarepta (NASDAQ: SRPT) reported that its gene therapy—which is designed to work the same way as Solid’s SGT-001—helped the first three patients it treated produce an average of either 38.2 percent or 53.7 percent, as measured by two different diagnostic tests, of normal levels of micro-dystrophin after three months.
Those numbers got better over time, and Sarepta reported indications—albeit, rife with caveats—that those expression levels might be leading to an actual benefit for patients. Sarepta has begun the first of the two final studies it will need to win FDA approval of its gene therapy, placing it ahead of Solid and Pfizer (NYSE: PFE), the third company developing a Duchenne gene therapy. Pfizer has yet to report human data.
It’s important to note that the gene therapy dose Sarepta has tested and is taking forward is four times higher than the one Solid has used. Solid picked its initial dose hoping it would prove effective for patients of all ages, without risking any safety problems, its spokesperson says. It is “engaging with the appropriate groups” to try to test higher doses as quickly as possible. The company has the drug supply and manufacturing capabilities to produce higher doses “without delay,” and plans to share more data later this year, the spokesperson said.
But that strategy comes with caution. Last year, the FDA halted testing of Solid’s gene therapy after a patient’s platelet and blood cell counts dropped dangerously low. Solid was ultimately cleared to resume testing, but had to amend its trial protocol to give patients steroids in the initial weeks following treatment, and make the expensive Alexion Pharmaceuticals (NASDAQ: ALXN) drug eculizumab (Soliris) available if there were signs of an immune reaction.
The good news, so far, is that Solid hasn’t seen any other safety problems arise in the three patients. Based on that and Solid’s preclinical work, “we believe we’ll be able to dose escalate successfully,” its spokesperson said.
But it’s still an open question whether issues will emerge as it cranks up the dose to try to keep pace with Sarepta, or how long it will take to produce a competitive result. Schwartz wrote last week that a less than 10 percent expression level of micro-dystrophin “neither meets management expectations nor does it provide reassurance” that the next dose tested would be comparable to what Sarepta’s rival gene therapy has produced so far. More likely, a “third or fourth dose” might be necessary to compete with Sarepta under such a scenario, which would “greatly bolster investor fears of dose-dependent toxicity issues,” Schwartz wrote.
“We believe this calls into question whether the [technical] differences” with Solid’s gene therapy will prevent it from producing the type of results Sarepta has, RBC Capital Markets analyst Brian Abrahams wrote in a note Thursday morning. “This should help reaffirm [Sarepta’s] potential leadership position in the space.”
Duchenne afflicts some 300,000 boys worldwide, puts them in wheelchairs by their teenage years, and typically kills them at a young age from lung or heart problems. The only available treatments are steroids and, for a subgroup of patients, another product from Sarepta called eteplirsen (Exondys 51). These treatments can slow progression but do not change the course of the disease. Gene therapy, ideally, could do that.