Over a 12-week period, the safety profile of a subcutaneous formulation of ocrelizumab was consistent with its original intravenous formulation, along with comparable MRI activity in the brain.
Positive findings were announced from the phase 3 OCARINA II trial (NCT05232825), as treatment with ocrelizumab (Ocrevus; Roche), an FDA-approved therapy for multiple sclerosis (MS), met its primary and secondary end points of noninferiority when used in combination with Halyzme Therapeutics ENHANZE drug delivery technology. Roche plans to share additional data from the trial at an upcoming medical meeting and will submit the findings for regulatory approval.1
The global, multicenter study included 236 patients with relapsing MS or progressive MS assessing ocrelizumab with ENHANZE as a twice a year 10-minute subcutaneous injection. All told, after a 12-week treatment period, results showed that efficacy of ocrelizumab co-formulated with ENHANZE, a proprietary recombinant human hyaluronidase enzyme, rHuPH20, was non-inferior to ocrelizumab given by intravenous infusion, as measured by pharmacokinetic levels.
"We are delighted that these positive Phase 3 data for OCREVUS administered subcutaneously with ENHANZE opens up the potential for people living with multiple sclerosis to receive their treatment in just 10 minutes, twice a year," Helen Torley, ChB, MRCP, president and chief executive officer at Halozyme, said in a statement.1 "Regulatory Authority approval of subcutaneous administration of OCREVUS with ENHANZE would create the possibility to administer OCREVUS in additional MS centers without IV infrastructure or with IV capacity constraints."
Secondary end points of the study included maximum serum concentration of ocrelizumab, total number of active, gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, safety, immunogenicity, and biomarker outcomes. Over a 12-week treatment period, ocrelizumab subcutaneous injection was comparable to the intravenous formulation in controlling MRI lesion activity. In addition, the safety profiles for the subcutaneous injection were comparable to that observed with the intravenous formulation.
For the intravenous group, the first dose of ocrelizumab was administered as 2 intravenous infusions given 14 days apart, with subsequent doses administered as subcutaneous injections. Those in the subcutaneous group received their first dose of ocrelizumab as one subcutaneous injection, with all subsequent doses administered the same way. Both groups have a recommended minimum of 22 weeks between subcutaneous doses.
Patients in the study had Expanded Disability Status Scale (EDSS) scores between 0-6.5 at screening, and had neurological stability for at least 30 days prior to both screening and baseline. In addition, individuals with EDSS less than 2 had disease duration from onset of MS symptoms of less than 15 years. For female participants, those without reproductive potential may be included if post-menopausal, unless they had received a hormonal therapy for menopause or if they were considered surgically stable.
Five products have received regulatory approvals in the US and/or global markets as subcutaneous products utilizing the ENHANZE drug delivery technology. They include: daratumumab and hyaluronidase (Darzalez; Janssen), trastuzumab and trastuzumab subcutaneous (Herceptin; Roche), immune globulin infusion 10% (Hyqvia; Takeda Pharmaceuticals), pertuzumb and trastuzumab (Phesgo; Roche), and rituximab (Rituxan; Roche). With the technology, clinicians are able to bypass traditional subcutaneous limitations and rapidly deliver high-dose, high-volume therapeutics to patients who need it in clinic or at home.2