28 April 2020 - Has Novo Nordisk shot itself in the foot?

In November 2019, the PBAC considered an initial major submission from Novo Nordisk for its new GLP-1 agonist semaglutide (Ozempic). The submission requested a PBS (Authority required (STREAMLINED)) listing for semaglutide for treatment of patients with type 2 diabetes mellitus who have inadequate glycaemic control, as dual therapy in combination with metformin hydrochoride or a sulphonylurea where either of these is contra-indicated or not tolerated; or as triple therapy in combination with metformin hydrochloride and a sulphonylurea.

Listing was requested on a cost effectiveness basis for (high dose) semaglutide compared to exenatide once weekly.

The PBAC’s recommendation for listing in terms of the cost effectiveness of semaglutide was that it would be acceptable if it were cost minimised against dulaglutide.

"Under Section 101(3B) of the National Health Act 1953, when the proposed medicine is substantially more costly than an alternative therapy, the committee cannot make a positive recommendation unless it is satisfied that, for some patients, the proposed medicine provides a significant improvement in efficacy and/or reduction of toxicity over the alternative therapy. The PBAC considered that there was insufficient evidence to accept a superiority claim for semaglutide over dulaglutide and that there was low certainty in the modelled benefits over both exenatide and dulaglutide. The PBAC therefore recommended semaglutide on the basis of non-inferiority to dulaglutide."

The recommended equi-effective doses for the cost minimisation to dulaglutide, when used in combination with metformin hydrochloride (dual therapy) and in combination with metformin hydrochloride plus a sulphonylurea (triple therapy), is semaglutide 1.0 mg once weekly is equi-effective to dulaglutide 1.5 mg once weekly.

"The PBAC did not consider that the proposal for the same price for both presentations of semaglutide was supported and pricing of the 0.5 mg dose of semaglutide would be determined by the Department according to usual methods."

In its Public Summary Document, the PBAC did not comment on equi-effective doses for semaglutide when used in combination with a sulphonylurea.

In the light of this, Novo Nordisk prepared and lodged a minor resubmission with a request for the PBAC to review its advice on the therapeutic relativities and equi-effective doses of semaglutide and dulaglutide for use in combination with metformin hydrochloride and/or a sulphonylurea for the treatment of patients with type 2 diabetes mellitus.  The resubmission was considered by the PBAC in March 2020.

"The PBAC recommended that semaglutide 0.5 mg should be considered equi-effective to dulaglutide 1.5 mg for treatment of patients with type 2 diabetes mellitus who have inadequate glycaemic control as dual therapy in combination with metformin hydrochloride."  

The PBAC is yet to comment on the equi-effective doses for use in combination with a sulphonylurea or in combination with metformin hydrochloride and a sulphonylurea but they are likely to be same as that for use in combination with metformin hydrochloride. 

The task for Novo Nordisk to proceed to a PBS listing for semaglutide just got harder. Sponsors need to think twice (even three times) when going back to the PBAC to challenge a therapeutic relativity/equi-effective dose. A very salient learning for others.