The PBS will subsidise rozanolixizumab (Rystiggo) for generalised myasthenia gravis from July, with around 4,900 Australians expected to benefit each year.
The listing gives neurologists a new anti-FcRn option for adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive, according to the TGA-approved Product Information.
Rozanolixizumab works by blocking the neonatal Fc receptor (FcRn), which normally protects IgG from degradation and recycles it back into circulation. By inhibiting that recycling, the drug drives down total IgG, including the pathogenic autoantibodies that underlie gMG. In clinical studies, weekly dosing produced a maximum 73% reduction in total IgG at around three weeks, with levels returning towards baseline about eight weeks after stopping treatment.
Per the PI, the drug is given as a subcutaneous infusion once weekly for a six-week cycle, at a dose tiered by body weight from 280mg to 840mg. Further cycles are then repeated according to symptom recurrence rather than on a fixed schedule. Clinicians must discontinue treatment if a patient shows no response, defined as a fall of at least two points on the MG-ADL scale, after three six-week cycles.
Rapid response in pivotal trial
The PBS listing rests on the phase 3 MG0003 trial, a randomised, placebo-controlled study of 200 patients followed for up to 18 weeks. On the primary endpoint, change in MG-ADL score from baseline to Day 43, the approximately 7mg/kg dose group improved by a mean of 2.586 points more than placebo (95% CI -4.091 to -1.249, p<0.001).
Clinical responders, defined as a two-point or greater improvement in MG-ADL, made up 71.9% of the rozanolixizumab group compared with 31.3% on placebo. Response came quickly: at least 39% of patients showed an MG-ADL improvement as early as Day 8, one week after the first infusion.
Subgroup data suggested similar benefit regardless of antibody status, with MuSK-positive patients recording a 100% MG-ADL responder rate at Day 43 in a small sample of five patients, against 14.3% on placebo. Efficacy also held up in patients aged 65 and over, who made up roughly a quarter of the study population.
Safety signals to watch
Headache, diarrhoea and pyrexia were the most common adverse reactions, with headache reported in 41.4% of treated patients across the pivotal trial versus 19.4% on placebo. The Product Information also flags aseptic meningitis as a risk, reported in 0.5% of patients (1 in 196) in the open-label extension study and listed as “not known” frequency from post-marketing reports. Clinicians are advised to work up any patient presenting with symptoms consistent with the condition according to standard of care.
Immunogenicity is common with repeated cycles. Antidrug antibodies developed in 26.9% of patients after one treatment cycle, rising to 61.4% after five cycles, though the sponsor reports no apparent impact on efficacy or overall safety.
Because rozanolixizumab lowers IgG, the Product Information advises against live or live-attenuated vaccines during treatment, and recommends spacing other IgG-based therapies, including IVIg, at least two weeks from a Rystiggo infusion to avoid reduced efficacy.
PBS restrictions
The listing sits under the Section 100 Highly Specialised Drugs Program for private hospital use, with an authority required and prescribing limited to specialists managing neuromuscular or neuro-inflammatory disorders. PBS restrictions cap subsidised access to three settings: three months of acute treatment for severe gMG, six months of bridging therapy, or continuous treatment for refractory disease, with patients only able to move forward through these phases, not back.
Switching between the three PBS-listed gMG biological agents, ravulizumab, rozanolixizumab and zilucoplan, is permitted when a patient moves between treatment settings, or in the treatment-refractory setting where a patient has tried one biologic without response or with intolerance.
The Department of Health and Aged Care lists a dispensed price of $219,238.80 for an 18-pack authority prescription, with patients paying the standard PBS co-payment of up to $25 per script, or $7.70 for concession card holders. Without the subsidy, the department estimates patients could pay up to $10,000 per pack.
Health Minister Mark Butler, announcing the listing alongside nine other new and expanded PBS entries for July, said the changes would give patients more options and financial relief.
“These medicines will give Australians with cancer and chronic conditions more treatment options to manage their health and provide vital financial relief to Australians battling these conditions,” he said.
Rozanolixizumab is listed under the brand name Rystiggo, sponsored by UCB Pharma and available as a single-use 140mg/mL vial.