Orchard Plans OTL-200 European Launch, FDA BLA Strategy

Orchard Therapeutics released its plans for 2021, which included the launch of OTL-200 (Libmeldy) in Europe for patients with metachromatic leukodystrophy (MLD). In the United States, the company expects to complete additional interactions with the FDA by mid-2021 to determine the path to a biologics license application (BLA) filing for OTL-200.

OTL-200 is manufactured from hematopoietic stem and progenitor cells (HSPC) transduced with a lentiviral vector to encode the ARSA gene. In January, the therapy received a Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA, which is expected to expedite the BLA process. OTL-200 was approved by the European Commission in December 2020 for early onset MLD.

In addition to these milestones, Orchard highlighted success from earlier in the year, including new data released at the 2021 WORLDSymposium for its autologous hematopoietic stem cell gene therapies OTL-203 and OTL-201. Moreover, the company noted that $150 million in additional funding that was previously announced is expected to support the company's operations until 2023.

“It is gratifying to witness the positive momentum Orchard has already established in early 2021, driven by solid execution," Frank Thomas, president and chief operating officer, said in a release. "Our compelling data in neurodegenerative disorders at the WORLDSymposium and successful completion of the $150 million financing exemplify this recent progress and showcase a growing appreciation for the potential of HSC gene therapy. We look forward to continuing our work in the year ahead and delivering further benefit for patients and our shareholders."

Proof-of-concept results for OTL-203 in patients with MPS-I Hurler syndrome (MPS-IH) were presented at the WORLDSympsium meeting in February. Data were available for 8 patients treated with the gene therapy, with follow-up reaching 1.5 years in some cases. All patients showed stable cognitive performance post-treatment, including longitudinal growth that was within age-appropriate reference ranges. Motor function was also found to stabilize with OTL-203 and there was improved range of motion in all patients.

Enzyme replacement therapy (ERT) was discontinued prior to the study and no patients had needed to restart the treatments following OTL-203. Overall, the gene therapy was well tolerated and IDUA antibodies present at baseline from ERT were no longer identifiable in all 8 patients at 2 months.

Based on these proof-of-concept data, Orchard is planning the launch of a registration-enabling study for OTL-203 in MPS-IH by the end of 2021. The company will be meeting with the FDA and European Medicines Agency (EMA) before the end of the year to identify an optimal path forward for OTL-203.

“For the majority of patients with MPS-I Hurler, existing therapeutic options such as enzyme replacement therapy and HSCT often fail to adequately address the disease’s impact on cognition, motor skills, and growth,” investigator Bernhard Gentner, MD, at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), said in a statement when the data were released. “With follow-up data showing stable cognitive performance and normal longitudinal growth in multiple patients treated with OTL-203, we are encouraged by the potential for HSC gene therapy to correct a wide spectrum of multisystemic manifestations of the disease and bring clinically meaningful benefit to patients.”

Additional proof-of-concept findings were presented at the WORLDSymposium for OTL-201 in patients with mucopolysaccharidosis type IIIA (MPS-IIIA, or Sanfilippo syndrome). In these early biomarker results for 3 patients, SGSH enzyme expression was seen on leukocytes and CD15+ cells increased from undetectable at baseline to greater than normal levels at 3 months. Moreover, urinary GAG levels declined to the normal range for the first 2 patients with assessable data. There were no treatment-related serious adverse events observed in the study.

“With a growing body of clinical data demonstrating cognitive and motor function within the normal range in multiple conditions, the potential for HSC gene therapy to make a durable impact in devastating disorders of the central nervous system has never been so compelling," Bobby Gaspar, MD, PhD, chief executive officer of Orchard, said in a statement when the data were released.

In January 2021, Orchard announced an exclusive agreement with GenPharm Services and GEN to facilitate access to OTL-200 in qualified treatment centers in Saudi Arabia, Kuwait, UAE, Qatar, Bahrain, Oman, and Turkey. Moreover, in March 2021, the company entered a multi-year alliance with Be The Match BioTherapies, to further support the European launch of OTL-200. Be The Match BioTherapies had supported therapy development through the clinical trials for the gene therapy.

“HSC gene therapies are personalized medicines that require precision to harvest a patient’s cells, transfer the cells to a lab for genetic modification and then return the gene-corrected cells back to a qualified treatment center to infuse into the patient,” Braden Parker, chief commercial officer of Orchard, said in a statement. “As we move into the launch phase for Libmeldy in Europe, we are pleased to continue our collaboration with Be The Match BioTherapies to help enable us to maintain the efficient, high-quality supply chain necessary to deliver Libmeldy to MLD patients in need.”

In addition to these therapies, Orchard also announced plans to submit a marketing authorization application to the EMA or OTL-103 in Wiskott-Aldrich syndrome (WAS) by the end of 2021. It also plans to submit a BLA for the medication by the end of 2022. However, pivotal data for the agent are still pending.