Just two weeks ago, Novartis’ cell therapy Kymriah (tisagenlecleucel-T) got a green light for use on the NHS in children and young people with acute lymphoblastic leukaemia (ALL).
NHS England’s chief executive Simon Stevens called it a “true game changer” and said patients in England would be among the first in Europe to benefit from the revolutionary new treatment.
However today England’s cost effectiveness watchdog NICE has issued a draft ruling that the CAR-T therapy cannot be recommended because it is not cost effective in diffuse large B cell lymphoma (DLBCL), a much larger patient group.
This is far from surprising – NICE has already come to the same preliminary conclusion about its CAR-T rival, Gilead’s Kymriah in DLBCL on 28 August.
NICE has raised the same concerns about both drugs in its initial appraisals, saying they both currently rely on single arm trials with no comparator, and have no long-term outcome data, making it hard for it to come to clear conclusions about their cost effectiveness.
But the huge promise of these ‘living medicines’ means a deal is likely to be struck: up to half of all patients treated achieve complete response (CR) -where there is no trace of the cancer left – offering hope of a long term remission or even a cure.
Any drug which can demonstrate a cure or extend lives by many years is likely to gain NICE approval – though their high list prices – £282,000 per treatment in Kymriah’s case – will unquestionably be brought down in confidential price negotiations.
The NICE committee also raised concerns about the common adverse events experienced by patients taking Kymriah. Most patients had severe adverse events (over grade 3), including cytokine release syndrome. While CRS is manageable in most patients, the worst affected often need time in intensive care and require treatment for unstable blood pressure and circulation and other organ toxicity.
NHS England’s commissioning expert told NICE that healthcare professionals would require “extensive training in managing and supporting patients” who had received CAR-T therapies, and that a new service specification is currently being developed to support this.
NICE says costs associated with managing and treating adverse events should therefore be reflected in its cost-effectiveness modelling.
NICE’s Meindert Boysen
Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE, says: “We have seen promising results for CAR-T therapies in early trials and believe there is great potential for tisagenlecleucel-T to help people who have not responded to other forms of therapy.
“Although we could not recommend tisagenlecleucel-T for adults with lymphoma, we welcome further discussions around the cost-effectiveness of the treatment and engagement with stakeholders.”
NICE says the committee will consider comments received on the draft guidance, together with any new evidence, at its next meeting on 23 October 2018.
This leaves the appraisal of Gilead’s Yescarta just a month ahead of its rival, with the second appraisal meeting on it scheduled for 27 September.
This adds to Gilead’s advantage in clinical trial data, where its Yescarta looks to have significantly better rates of overall response rate and complete response.
Gilead’s managing director for the UK and Ireland Hilary Hutton-Squire told PME that she is confident of agreeing a deal, with access via the Cancer Drugs Fund (CDF) the likely route.
In any event, NHS England will be keen to either play one company off another, or otherwise encourage price competition.
A spokesperson for Novartis said: “While we are disappointed with this preliminary decision, we recognise that this one-time therapy is an innovative and radically different treatment approach with curative intent, and it may be challenging to adequately compare Kymriah to current treatments for patients with this type of blood cancer who have limited options.”
The company also pointed out an inconsistency in NICE’s appraisals of the rival treatments: Yescarta has been deemed eligible for NICE’s special ‘end of life’ criteria in its appraisal, but Kymriah had not.
“We were surprised that NICE have not supported the “end of life” criteria for this population of DLBCL patients and strongly disagree with this decision. This relates to individuals who have already failed two previous therapies, and for the vast majority of this population, life expectancy can be counted in months rather than years. This is in contrast to a recent review for the same class of treatment and population of patients.”
Novartis concluded by saying it would work with NICE to define the most relevant comparator studies and reconsider the “end of life” decision, which it hopes could result in a final ‘yes’ for the therapy.
One final factor is the complexity and difficulty of producing CAR-Ts: Novartis has indicated limited manufacturing capacity for Kymriah means it will focus first on supplying its smaller ALL patient population in Europe, which could give Gilead space to establish itself in DLBCL in these markets.