Orchard Therapeutics Presents Two-Year Follow-Up Data Versus Historical Control from Registrational Trial of OTL-101 for the Treatment of ADA-SCID
100% Overall Survival and 100% Event Free Survival in Patients Treated with OTL-101 Compared to 88% OS and 56% EvFS with Historical HSCT Overall at 24 months
Biologics License Application Submission Planned for the U.S. in 2020
BOSTON and LONDON,
ADA-SCID is a rare, life-threatening, inherited disease caused by mutations in the ADA gene. Deficiencies of the ADA enzyme leads to dysfunction of cells of the immune system, including B, T and natural killer cells. Patients with ADA-SCID are unable to fight off and frequently succumb to complications from bacterial, viral and fungal infections.
“With some patients in this trial approaching 5 years of follow-up, treatment with OTL-101 continues to be well-tolerated with higher rates of overall and event free survival for patients with ADA-SCID compared to a historical control group of patients receiving hematopoietic stem cell transplants,” said
The reported data are the complete 24 month results from a trial evaluating the safety and efficacy of OTL-101. OTL-101 was administered post-busulfan conditioning in 20 pediatric patients, who lacked a medically eligible donor for bone marrow transplantation. Patients were followed for 24 months post treatment and compared with a historical control cohort of 26 patients with ADA-SCID who underwent hematopoietic stem cell transplant (HSCT), 12 from matched related donors (MRD) and 14 without a MRD. The median age at treatment for patients receiving OTL-101 was 9.0 months and 7.3 months for patients treated with HSCT.
• Treatment with OTL-101 resulted in 100% overall survival (OS) and 100% event free survival (EvFS) at 24 months
- For OS, there was a difference of 12% (95% CI: -5.6, 31.2, p = 0.121) between the patients treated with OTL-101 compared with HSCT overall
- For EvFS, there was a statistically significant difference of 44% (95% CI: 22.8, 65.2, p = 0.001) between the patients treated with OTL-101 compared with HSCT overall
• Genetically modified cells, as indicated by increasing and then sustained vector copy number in both peripheral blood mononuclear cells and granulocytes, were detectable in all patients treated with OTL-101 and were maintained through 24 months post-treatment. A similar pattern was observed in ADA enzyme activity.
• Evidence of immune reconstitution was observed in patients treated with OTL-101
- By 24 months post-treatment, 90% of patients receiving OTL-101 were able to stop immunoglobulin replacement therapy compared with 55% receiving HSCT overall
- Over 24 months, none of the patients treated with OTL-101 restarted enzyme replacement therapy (ERT) after stopping 30 days post-treatment per protocol, whereas three patients in the historical control group received long-term ERT after HSCT and seven required additional rescue HSCT
• Treatment with OTL-101 was well-tolerated and had a positive benefit-risk profile
• There were no deaths or reports of graft-versus-host disease (GvHD) in the patients treated with OTL-101
- In the historical HSCT control group, five acute and three chronic GvHD events were reported, including one death due to GvHD
• Nine out of the 20 patients who received OTL-101 experienced a total of 27 serious adverse events (SAEs)
- The most frequent SAEs were infections and gastrointestinal events
- One SAE of bacteremia was deemed related to treatment with OTL-101 and resolved with antibiotics
- Two cases of immune reconstitution inflammatory syndrome were deemed unrelated to OTL-101 and resolved with corticosteroids
About ADA-SCID and OTL-101
Severe combined immune deficiency due to adenosine deaminase deficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the ADA gene resulting in a lack of, or minimal, immune system development.1-4 The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive, and without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births in
Orchard’s portfolio of autologous, ex vivo, hematopoietic stem cell gene therapies includes Strimvelis, the first such treatment approved by the
Orchard currently has offices in the
This press release contains certain forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as “anticipates,” “believes,” “expects,” “intends,” “projects,” “anticipates,” and “future” or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, Orchard’s expectations regarding timing of discussions with regulatory authorities in the U.S. and the timing of regulatory submissions for approval of its product candidates, including OTL-101; Orchard’s views with respect to the potential for OTL-101 for the treatment of ADA-SCID; its expectations regarding the reporting and outcome of data from its clinical trials, and the regulatory pathway for ADA-SCID. These statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond Orchard’s control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the success, cost, and timing of Orchard’s product development activities and clinical trials, including that prior results, such as safety or durability of effect, observed from prior studies or clinical trials will be replicated or will continue in ongoing or future studies or trials involving Orchard’s product candidates, and Orchard’s ability to obtain and maintain regulatory approval for its product candidates. Orchard undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law. For additional disclosure regarding these and other risks faced by Orchard, see the disclosure contained in Orchard’s public filings with the Securities and Exchange Commission.
1Orphanet. SCID due to ADA deficiency 2Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314. 3Kwan A, et al. JAMA. 2014;312:729-738. 4Sauer AV, et al. Front Immunol. 2012;3:265.
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Source: Orchard Therapeutics Limited