NICE issues draft ‘no’ on first quadruplet combination for England & Wales

The National Institute for Health and Care Excellence (NICE) has issued a draft ‘no’ on the treatment of daratumumab (Darzalex®) in combination with thalidomide, bortezomib (Velcade®) and dexamethasone for the treatment for newly diagnosed myeloma patients receiving high-dose therapy and stem cell transplantation (HDT-SCT).

The first-in-kind quadruplet combination is currently available in Scotland having been approved by the SMC in January 2021.   Access for patients in Northern Ireland will be based on the final decision from NICE.

Clinical trial results show that adding daratumumab to the standard induction treatment of bortezomib, thalidomide and dexamethasone improves patient outcomes and extends the time before relapse.  Although the NICE appraisal committee agreed that the treatment was effective, they reported some uncertainties in the longer-term data required to make the cost-effectiveness assessment which doesn’t yet demonstrate how long a remission the treatment will deliver, or how long it might extend life overall.

Commenting on the decision, Laura Kerby, Myeloma UK Chief Executive, said:

“We are disappointed by this decision from NICE and will continue to work to turn this draft ‘no’ into a ‘yes’.  Whilst we appreciate this is a challenging appraisal, we firmly believe that patients across the UK should have equal access to the most effective treatments and will keep fighting to achieve this.”

Rosie Dill, patient expert said:

“Whilst it is obviously disappointing that NICE decided not to approve this new drug combination, I was pleased to see that the committee had such a good understanding of myeloma and its impact on patients, families and carers. It was clear that Myeloma UK has already done much to raise awareness of the disease. When NICE reviews their decision I hope the outcome will be a positive one, as the results presented from trial look very promising.”

The decision is now out for consultation and is available for review and comment by stakeholders. Myeloma UK are reviewing materials in support of the use of the quadruplet combination and will continue to work with patients, clinicians NICE and the manufacturers to secure approval.

What about the rest of the UK?

The treatment combination was approved for patients in Scotland by the SMC in January 2021. The department of health in NI will decide on whether to fund this treatment based on the decision from NICE.

NICE no recommendation DVTd FAQ’s 

What happens now?

NICE have issued the draft decision in an Appraisal Consultation Document (ACD) and will now ask questions that could turn the draft ‘no’ into a final approval. Most myeloma drug approvals result in an initial draft “no” so unfortunately this step in the process is not unusual.

Myeloma UK will continue to work with clinicians, the company and with NICE and will respond to the consultation, making the case for Daratumumab in combination with bortezomib, thalidomide and dexamethasone to be approved.  Once NICE has gathered views from all stakeholders (deadline 18 June), it will meet again to consider its decision. The date for this meeting has not yet been decided.

For more information please see our blog from an earlier appraisal on ‘What happens after a draft ‘no’?‘

Why did NICE say no?

The committee highlighted that results from the clinical trial (CASSIOPEIA) show that adding daratumumab to the standard induction treatment of bortezomib, thalidomide and dexamethasone improves progression free survival and overall survival.

However NICE considered that uncertainty remains about the long-term impact of the daratumumab treatment effect which makes the cost effectiveness estimates uncertain. Further to this modelling for long term overall survival did not consider the recent NICE approvals to the myeloma treatment pathway.

The price of drugs is a factor in NICE decisions, but it is important to bear in mind that they do not look at whether a drug is expensive, rather they look at whether it is cost effective; all NICE decisions are based both on the clinical effectiveness and cost effectiveness of the treatment being appraised compared to the current standard of treatment.

Can the treatment be approved through the Cancer Drugs Fund (CDF)?

The committee considered this quadruplet combination for approval through the CDF and noted that the final data analysis of the CASSIOPEIA trial is due in 2023.

The committee stated that the key clinical uncertainty concerning the duration of the daratumumab treatment effect could not be resolved with greater certainty after 5 years of follow up. However the question of whether it could be funded via the Cancer Drugs Fund is yet to be finally decided.

Is it likely to be approved?

During the consultation period the company, Janssen, clinicians, and Myeloma UK will be able to submit further evidence to address NICE’s concerns. The company is also able to come forward with new information which could address the uncertainties highlighted by the committee.

At the moment, we cannot be certain what the outcome will be. It is positive that NICE recognise the clinical benefits that this quadruplet combination can deliver, but there is still work to be done to resolve the concerns NICE have about its cost-effectiveness. We will continue to work with clinicians, NICE and with the company to make a case for its approval.

What about patients based in Scotland and Northern Ireland?

Daratumumab in combination with bortezomib, thalidomide and dexamethasone as an induction treatment for newly diagnosed patients with myeloma who are eligible for a stem cell transplant, was approved by the Scottish Medicines Consortium in January 2021.

For patients based in Northern Ireland the Department for Health makes decisions on which treatments to fund through the NHS. They can follow guidance issued by NICE and the SMC but normally follow the guidance issued by NICE.