1 April 2022 - The Public Summary Documents (positive recommendations and subsequent decisions not to recommend) from the December 2021 PBAC intracycle meeting are now available.

Don't get too excited; there are only two!

Having said that, the Public Summary Document for Trikafta is surely an interesting read. It is not that easy to compress 26 pages of very complex content into a short summary but here we go!

Background

Trikafta was registered by the TGA on the 24 March 2021 for the treatment of patients aged 12 years and older with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene (F/any population).

In March 2021, the PBAC considered a request from Vertex Pharmaceuticals to list Trikafta on the PBS for the F/any population which encompassed five patient sub-populations: 

• Patients with CF who are homozygous for the F508del CFTR mutation (F/F population)
• Patients with CF who are heterozygous for F508del in the CFTR gene with a residual function mutation (F/RF population)
• Patients with CF who are heterozygous for F508del in the CFTR gene with a gating mutation (F/G population)
• Patients with CF who are heterozygous for F508del in the CFTR gene with a minimal function mutation (F/MF population)
• Patients with CF who are heterozygous for F508del in the CFTR gene with a second mutation that is unknown or not yet characterised as gating, residual function or minimal function (F/not yet characterised)

The PBAC assessed the clinical and cost effectiveness of all five patient sub-populations.

July 2021

The PBAC recommended the PBS listing of Trikafta for only the F/MF population.  The recommended was made in order to facilitate access to Trikafta for a patient population that does not currently have access to treatment. Vertex Pharmaceuticals chose not to proceed to PBS listing based on this recommendation.

December 2021

The early re-entry resubmission sought the PBS listing of Trikafta for the F/any population.

The PBAC noted that the resubmission was not consistent with the Committee’s advice in March 2021 and May 2021 in relation to the F/any population with regard to the cost effective price and the patient estimates.

Notwithstanding this, the Committee recommended the PBS listing of Trikafta for F/any population. The PBAC considered that Trikafta could be brought within an acceptable ICER range with a price reduction, and in the context of accepting the resubmission’s proposed patient estimates as reflecting the upper end of the range of likely use.

The PBAC noted a key driver of the ICER was the cost of Trikafta and that its cost would be reduced by 90% after 16.35 years to account for potential generic competition. The PBAC has previously considered the application of such price reductions to be inappropriate and contrary to the PBAC Guidelines. The PBAC further considered that experience with CFTR modulator treatments indicates that it is highly unlikely that this price reduction would be realised, in part due to future patients being treated with alternative newer therapies.

The PBAC recalled that an ICER of around $155,000 - $255,000/QALY gained had previously been accepted for the first generation CFTR modulator treatments – ivacaftor (Kalydeco) for the F/G population, lumacaftor with ivacaftor (Orkambi) for the F/F population and tezacaftor with ivacaftor (Symdeko) for F/F and F/RF populations. At the time of their listing, these treatments represented highly novel products for a disease with no other treatment options. The resulting prices for these were based on extremely optimistic assumptions in the modelled economic evaluation, including the assumption of a 90% price reduction at patent expiry. This effectively means that the true ICER for these medicines has very likely been greater than previously estimated.

Given the substantial increase in cost associated with the listing Trikafta on the PBS for the F/any population, the associated large opportunity cost, and that the 90% price reduction assumed in the modelled economic evaluation was inappropriate and very unlikely to be achieved, the PBAC considered that a price reduction would be required to ensure reasonable confidence that a high but acceptable ICER would be achieved. 

The PBAC advised that an risk sharing agreement with subsidisation caps based at the level of the financial estimates should apply given the high financial impact, with a 100% reimbursement over the caps to ensure budget certainty.

In response to the PBAC's recommendation, Vertex Pharmaceuticals provided a listing proposal for Trikafta to the Department offering a weighted annual price (information on the price has of course been redacted). The proposed price was higher than the price calculated based on the PBAC advice in December 2021, however it represented the lowest price offered by Vertex Pharmaceuticals for Trikafta to date. Vertex Pharmaceuticals characterised this as its final offer.

February 2022

The Department sought the advice of the PBAC in an out of session meeting in February 2022, as to whether the pricing proposal from Vertex Pharmaceuticals was acceptable.

The PBAC noted that the latest pricing proposal of Vertex Pharmaceuticals for Trikafta still resulted in very high ICERs, especially in relation to the F/MF and F/F sub-populations. The Committee advised that the latest proposal of Vertex Pharmaceuticals was acceptable, taking into consideration the high clinical need for the treatment, particularly for those patients currently ineligible for a PBS subsidised CFTR modulator treatment; and recognising that Trikafta is an effective treatment that provided a significant benefit for some patients.

April 2022

The Minister of Health issued a press release stating that from 1 April 2022, Trikafta will be listed on the PBS for the F/any population.

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