Solid Biosciences announced today plans to move to a higher dose of SGT-001 in IGNITE DMD, their Phase 1/2 clinical trial evaluating SGT-001 microdystrophin gene therapy as a potential treatment for Duchenne.

This decision is based on their initial look at the muscle biopsies from the first three boys who received the starting dose of SGT-001 in the clinical trial. All three boys who received SGT-001 continue to do well, and Solid continues to follow them as part of their study protocol. As for the biopsy data, Solid reported that they were able to see microdystrophin expression across some measures, although it was low. These initial results support moving forward with evaluation of higher doses in the clinical trial.

We appreciate Solid providing this update and are hopeful that this dose escalation will lead to greater microdystrophin expression. We look forward to learning more about this study at PPMD’s Gene Therapy Policy Forum in March.

Solid’s Letter to the Duchenne Community

Dear Duchenne Community,

Today we announced our intention to move to a higher dose of SGT-001 in IGNITE DMD, our Phase I/II clinical trial evaluating SGT-001 microdystrophin gene therapy as a potential treatment for Duchenne. This decision is based on our initial look at the muscle biopsies from the first three boys who received the starting dose of SGT-001 in the clinical trial. You can find the press release here. We wanted to take a moment to share with the Duchenne community what these findings mean and how we are moving forward.

First, we want to let you know that all three boys who received SGT-001 continue to do well, and we are following them per our study protocol. As for the biopsy data, we were able to see microdystrophin expression across some measures, although it was low. These initial results support moving forward with evaluation of higher doses in the clinical trial.

From the beginning, IGNITE DMD was designed as a dose escalation study meaning it is intended to evaluate SGT-001 at a series of progressively higher dose levels. This design allows us to uncover what may work best in boys with Duchenne in a thoughtful way. All the data we have from preclinical studies at different doses of SGT-001 suggest that microdystrophin expression will be greater at higher SGT-001 doses.

We are now working to expedite the planned dose escalation strategy that is outlined in the clinical trial protocol and begin evaluating a higher dose of SGT-001 in IGNITE DMD as soon as possible. Importantly, we have enough drug to do this successfully and without delay.

We believe SGT-001 has the potential to be a transformative therapy for patients with Duchenne, and we remain fully committed to moving forward as rapidly as possible. We are extremely grateful to the patients and families who choose to participate in our clinical efforts, and in all clinical studies aimed at improving the lives of patients with Duchenne.

We have included below some questions and answers that may help clarify this news. We look forward to providing an update soon.

Sincerely,

The Solid Team

Questions and Answers

Why didn’t you see higher dystrophin expression with the initial dose of SGT-001? What gives you confidence that a higher dose will work?

As you might know, IGNITE DMD was designed to evaluate multiple doses of SGT-001. You can see this from the clinical trial design image below. One goal of dose escalation studies with new and innovative technologies is to start with a dose level that maximizes safety while providing the potential for efficacy and then proceed to higher doses in a thoughtful manner to safely achieve maximum efficacy.

To select our starting dose, we studied SGT-001 extensively in preclinical disease models. Now we are able to combine our preclinical understanding of SGT-001 at higher doses with the data we communicated today to support the expectation that a higher dose will result in higher microdystrophin expression.

What are the next steps?

We are actively working with the appropriate groups to enable dose escalation as quickly as possible. With thoughtful planning, we already have the operations and drug supply in place to dose at higher levels without delay. We anticipate this to be a relatively quick process and will provide an update as soon as we can.

Can you update the community on the clinical trial site?

Our partnership with the University of Florida on IGNITE DMD remains strong and we continue to be profoundly thankful for Dr. Barry Byrne and his dedicated team.

What happens with the patients enrolled or waiting to be enrolled in IGNITE DMD?

The boys involved in the study are our number one priority. All activities at the University of Florida will continue as planned. The only change is that future patients may now receive a higher dose of SGT-001.

What does this mean for the boys who have already been dosed?

First and foremost, these boys continue to do well, and the early signals of microdystrophin expression, albeit low, are encouraging. We will continue to follow them per our study protocol to understand potential impact of SGT-001 on disease progression, as well as for long term safety.

Click here to read the full letter.

Read Solid’s Press Release

Solid Biosciences Announces Preliminary SGT-001 Data and Intention to Dose Escalate in IGNITE DMD Clinical Trial for Duchenne Muscular Dystrophy

CAMBRIDGE, Mass., Feb. 07, 2019 (GLOBE NEWSWIRE) — Solid Biosciences (Nasdaq: SLDB) announced today preliminary findings from IGNITE DMD, the Company’s Phase I/II dose-ascending clinical trial evaluating the safety and efficacy of SGT-001 microdystrophin gene transfer for the treatment of Duchenne muscular dystrophy (DMD). Initial three-month biopsy data showed low levels of microdystrophin protein expression. The Company is currently engaging with the appropriate parties to dose escalate as planned and as soon as possible.

“We believe that SGT-001 will be a meaningful treatment for patients with DMD and are confident we have the right approach in place to evaluate its potential at higher doses. We have already begun working to expedite the planned dose escalation strategy outlined in our clinical trial protocol,” said Ilan Ganot, Co-founder, Chief Executive Officer and President of Solid Biosciences. “This strategy is further supported by our scalable manufacturing process, from which we have sufficient drug product available to dose escalate without delay. We have the financial resources to execute on our plan and look forward to communicating additional data later this year.”

Preliminary analyses are based on three-month biopsy data from the first three patients dosed with 5E13 vg/kg of SGT-001, the lowest dose outlined in the study protocol. In one patient, microdystrophin was detected via western blot below the five percent level of quantification of the assay and in approximately 10 percent of fibers via immunofluorescence. There were also signs of co-localization of neuronal nitric oxide synthase (nNOS) and beta-sarcoglycan associated with microdystrophin expression. In the second and third patients, microdystrophin was detected via immunofluorescence at very low levels, but it was undetectable via western blot.

Six patients have been enrolled in IGNITE DMD, three to the active treatment group and three to the delayed treatment control group. The safety profile of SGT-001 remains unchanged and all patients continue to be followed per the study protocol.

“The patients who have received SGT-001 as part of the IGNITE DMD clinical trial are all doing well, and we are encouraged to explore higher doses moving forward,” said Dr. Barry Byrne, M.D., Ph.D., Professor of Pediatrics and principal investigator for IGNITE DMD. “It is extremely important to advance innovative research with the ultimate goal to bring therapies to patients with Duchenne muscular dystrophy.”

As previously disclosed, Solid believes that its existing cash, cash equivalents and available-for-sale securities as of September 30, 2018 will be sufficient to fund its operations through the first quarter of 2020.

Click here to read the full press release.