OBINUTUZUMAB

The PBAC recommended obinutuzumab for the treatment of patients with active class III or IV lupus nephritis with or without class V (based in ISN/RPS 2003 classification) who are receiving standard therapy with mycophenolate mofetil (MMF) and corticosteroids. 

The PBAC welcomed input from health care professionals and consumer and medical organisations highlighting the high clinical need for effective therapies for lupus nephritis. The PBAC acknowledged the impact of lupus nephritis on young women, First Nations people and individuals of Asian and African ancestry. The PBAC noted that lupus nephritis is not only more prevalent in First Nations people but is also associated with a significantly higher disease burden characterised by more severe disease, increased morbidity and higher mortality rates compared to people who are not of First Nations descent. The input outlined that obinutuzumab is associated with reductions in corticosteroid doses and described the clinical meaningfulness of the potential for reductions in corticosteroid related side effects and harms. 

The PBAC accepted that obinutuzumab was more effective than standard therapy at improving kidney function, such as improved rates of complete kidney recovery when compared with standard therapy alone. However, the REGENCY clinical trial showed that obinutuzumab had higher rates of side effects, including infections and reactions related to administering infusions.

In support of its requested price, the sponsor claimed that obinutuzumab would substantially reduce rates of kidney dialysis, transplants and deaths. However, the PBAC considered some of the assumptions of continued benefit beyond the trial duration for these outcomes were overly optimistic. As such, the PBAC advised obinutuzumab would be represent value for money with a price reduction reflecting more realistic estimates of some of the long term benefits and costs. 

The PBAC considered that revisions were also required to the submission’s financial estimates around the prevalence and assumptions about the number of patients who would start using obinutuzumab. The PBAC considered there was a significant risk that people would use obinutuzumab for a longer duration than estimated by the sponsor. The PBAC therefore advised that a risk sharing arrangement with the sponsor would be required to mitigate this risk.

The PBAC advised that the listing would necessitate a change to another PBS listing for anifrolumab, a medicine that treats systemic lupus erythematosus, to prevent combination use of anifrolumab with obinutuzumab.