Data Roundup: June 2024 Features Updates from ASCO and in Diabetes, Rare Disease, and more.

Last month, June 2024, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, neurology, rare diseases, and more.

As more and more innovative therapies enter the clinical trial field, more data is accrued every month, buoying excitement in the field and sometimes making or breaking the fates of small biotech companies. Last month delivered promising data updates presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting as well in diabetes, muscular dystrophy, and rare diseases. Our team has highlighted these and other updates below.

Click the read more buttons for more details and information about each update.

Genethon’s Duchenne Muscular Dystrophy Gene Therapy GNT0004 Produces Expression of Microdystrophin in Phase 1/2/3 Trial

June 22, 2024- Genethon’s GNT0004, an investigational recombinant adeno-associated virus (AAV) vector-based gene therapy intended to treated Duchenne muscular dystrophy (DMD), has demonstrated the ability to produce expression of microdystrophin, among other signs of efficacy, in a phase 1/2/3 clinical trial.

“DMD is a rare, X-linked progressive disease caused by mutations in the dystrophin gene, leading to dystrophin deficiency in muscles. The lack of dystrophin in myocytes results in progressive muscle degeneration that manifests primarily as muscle weakness and early death during the second or third decade of life, with the most common cause of death being cardiorespiratory failure," Francesco Muntoni, MD, the principal investigator of the trial and the chair of pediatric neurology at University College London Great Ormond Street Institute of Child Health, and colleagues wrote in their poster.

For the 3 patients who were treated at the higher dose, immunohistochemistry showed that a mean of 54% of muscle fibers (range, 15% to 85%) were expressing microdystrophin, the therapeutic transgene delivered by GNT0004, at 8 weeks posttreatment. Genethon noted that alongside these expression levels, a mean of 1.2 vector genome copies per muscle fiber nuclei (range, 0.4 to 2.5) were observed. Furthermore, at 12 weeks posttreatment for these patients, levels of CPK, a biomarker for muscular destress, had been reduced by a mean of 74% (range, 50% to 87%).

Vertex’s Diabetes Cell Therapy on Track to Meet Endpoint of Eliminating Severe Hypoglycemic Events

June 26, 2024- Data continue to support VX-880's (Vertex Pharmaceuticals) potential to eliminate or reduce the need for insulin use in patients with type 1 diabetes.

“This positive data adds to the growing body of evidence for VX-880’s potential to revolutionize the treatment of type 1 diabetes that would give patients an alternative solution other than exogenously administered insulin. These findings will also support further evaluation of VX-880, and we hope to see this treatment become a pivotal development in type 1 diabetes care," investigator Piotr Witkowski, MD, PhD, Professor of Surgery, Director, Pancreatic and Islet Transplant Program, University of Chicago, Illinois, said in a statement.

All 12 participants that received the full dose had improved glycemic control and achieved ADA-recommended targets for both HbA1c below 7.0% and time-in-range above 70% on continuous glucose monitoring. Most(n = 11) had reduced or no exogenous insulin use at their last visit and all had elimination of severe hypoglycemic events (SHEs) during the evaluation period. All 3 participants who have had at least 1 year of follow-up have met the primary endpoint of no SHEs with HbA1c less than 7.0% and the secondary endpoint of insulin independence. Of 10 participants who completed the Day 180 visit, 7 are no longer using exogenous insulin and 2 had around a 70% reduction in their daily insulin use.

Metastatic Colorectal Cancer CAR-T Therapy GCC19CART Demonstrates Safety and Clinical Activity in US Patients

June 4, 2024- GCC19CART (Innovative Cellular Therapeutics), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy, has demonstrated safety and clinical activity among patients with refractory metastatic colorectal cancerbeing treated in the phase 1 CARAPIA-1 clinical trial (NCT05319314).

“Preliminary results demonstrate that GCC19CART has an acceptable safety profile and meaningful clinical activity in refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented, including from patients treated at DL2," first author Benjamin L. Schlechter, MD, an instructor in medicine at Harvard Medical School and gastrointestinal oncologist at Dana-Farber Cancer Institute, and colleagues wrote.

The overall response rate was 40%, with 2 of 5 patients having achieved a partial response to the CAR-T. One other patient showed stable disease with a partial metabolic response observed on their PET/CT scan. In the 2 other treated patients, progressive disease was observed; although, it was noted that a falling tumor marker suggesting tumor flare was reported in 1 of these patients.

Intellia Successfully Redoses CRISPR Gene Editing Therapy

June 27, 2024- Intellia Therapeutics’ CRISPR editing therapy NTLA-2001 has demonstrated the ability to safely be redosed, according to new data from a phase 1 trial (NCT04601051) evaluating the therapy in patients with transthyretin (ATTR) amyloidosis.

“Today’s data showcase an exciting new platform advancement for Intellia and the field of gene editing. For the first time ever, we demonstrated that redosing with CRISPR, utilizing our proprietary, non-viral LNP-based delivery platform, enabled an additive pharmacodynamic effect on the target protein,” John Leonard, MD, President and Chief Executive Officer, Intellia, said in a statement.

The follow-on data were from the 3 initial patients enrolled in the dose-escalation portion of the phase 1 trial. The patients received 0.1 mg/kg of NTLA-2001, which led to an expected, lower-than-targeted 52% median reduction in serum TTR by day 28. These patients then opted to receive a 55 mg dose after 2 years of observation as according to study protocol. This dose led to the target pharmacodynamic effect and a 90% median reduction in serum TTR by day 28, representing a 95% median reduction from original baseline levels.

Pfizer’s Phase 3 Trial for DMD Gene Therapy Fordadistrogene Movaparvovec Misses the Mark on Primary End Point

June 13, 2024- Pfizer’s phase 3 CIFFREO study (NCT04281485) evaluating fordadistrogene movaparvovec (PF-06939926), an investigational adeno-associated virus (AAV) vector-based gene therapy expressing “minidystrophin”, failed to achieve its primary end point, according to an announcement from the company.

“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped. We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy," Dan Levy, MD, PhD, the development head for DMD at Pfizer, said in a statement.

CIFFREO did not demonstrate improvement in gross motor function on the North Star Ambulatory Assessment for patients treated with the gene therapy in comparison to patients treated with placebo at 1 year posttreatment, the measurement that constituted the trial’s primary end point. Pfizer additionally noted that the trial missed the mark on key secondary end points, with patients treated with fordadistrogene movaparvovec showing no significant difference in the change from baseline on 10-meter run/walk test velocity and time to rise from floor velocity compared to patients who received the placebo.