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Gilead optimistic about Yescarta deal in UK

Says NICE and NHS England understand groundbreaking nature of CAR-T

When NICE gave a rapid ‘no’ to Yescarta on 28 August, just one day after it gained EU-wide marketing approval, some commentators concluded England’s cost-effectiveness watchdog was displaying a worse-than-usual knee-jerk negativity.

That’s because Gilead’s CAR-T therapy is a potentially life-saving cancer therapy, wiping out all traces of advanced cancer in around half of the patients who received it in clinical trials.

Yescarta (axicabtagene ciloleucel) and its rival CAR-T therapy Novartis’ Kymriah (Tisagenlecleucel-T) were granted European approved on the same day in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) for patients who have progressed after two or more systemic therapies.

NICE is evaluating Yescarta in DLBCL just ahead of a separate appraisal of Kymriah, and quickly produced its preliminary decision not to recommend Gilead’s drug, arguing that its data hadn't demonstrated cost-effectiveness.

Novartis’ drug is also approved in a separate use in children and adolescents with B-cell precursor acute lymphoblastic leukaemia (ALL).

The snub to Yescarta seemed more acute the following week, when NHS England’s Simon Stevens announced Kymriah would be funded in ALL, and called it “a true game changer”.

But Gilead’s general manager for the UK and Ireland, Hilary Hutton-Squire, has taken a sanguine approach to NICE’s initial rejection of Yescarta.

Hilary Hutton-Squire

Hilary Hutton-Squire

“Like many breakthrough cancer treatments, we have some level of uncertainty around the data – uncertainty around the long-term overall survival (as the data is still evolving) and about what treatment to make a comparison with,” she told Pharmaceutical Market Europe.

She adds: “I think it would have been surprising if we had managed to resolve everything in one committee meeting”, and is optimistic that the uncertainty around the data can be resolved and an agreement can be reached soon.

Approved in the US around a year ago, the CAR-T therapies work by taking a patient’s own T cells, re-engineering them to fight cancer cells and then reinfusing them into the patient. These one-time treatments have shown remarkable results in lymphoma and leukaemia patients who have run out of all other options and have just months to live – up to half of patients in some trials seeing the cancer disappear completely.

However it’s not yet clear if the complete response (CR) seen in these patients will last long enough to be considered a ‘cure’, and their cost is high – Kymriah’s UK list price is £272,000 (€300,000), with Yescarta’s expected to be around the same level.

“I’ve been through many NICE appraisals, and I have not seen this level of engagement and excitement from NICE and NHS England and at the CDF.”

Gilead has been in talks with NICE, its ‘managed access’ Cancer Drugs Fund (CDF) committee and specialised medicines budget holder NHS England for many months in the run-up to the drug’s marketing approval.

Hilary Hutton-Squire counters any suggestion that this was just another case of NICE blocking a cancer drug because of its high cost, or that it had failed to grasp how groundbreaking a therapy it is.

“I’ve been through many NICE appraisals, and I have not seen this level of engagement and excitement from NICE and NHS England and at the CDF.”

Yescarta’s data

Gilead’s CAR-T therapy has produced some remarkable results in very sick patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) plus another, rarer variant, primary mediastinal large B-cell lymphoma (PMLBL).

Its pivotal ZUMA-1 trial involved patients who had progressed after two or more systemic therapies, and who are typically expected to die from the disease within six months.

Of the patients treated with a single infusion of Yescarta, 72% responded to therapy (overall response rate). Most remarkably, this included 51% of patients who had no detectable cancer remaining – a complete remission (CR).

Median overall survival hasn’t been reached yet, but more than half of patients are still alive 15 months after their single treatment – holding out the possibility that it could represent a cure for some patients.

These results have been rightly hailed as transformational - so why has NICE said no so quickly?

There were two topline reasons for this. Firstly, Yescarta’s pivotal ZUMA-1 trial was a single-arm, open-label study, and a lack of a comparator makes NICE’s cost-effectiveness modelling much harder. Secondly, the trial data isn’t yet mature, with the median overall survival (OS) not having been reached yet – a positive sign for patients, but not helpful for NICE aiming to get a precise calculation of its value.

Both sides are now looking to resolve these two questions. NICE wants to compare Yescarta to patients taking salvage chemotherapy but Gilead wants to make sure a suitable group is selected, otherwise the ICER cost-effectiveness score could be skewed.

Meanwhile, the immature data makes using the Cancer Drugs Fund the obvious option – the CDF is now a ‘managed access’ fund allowing drugs to be launched and to prove their cost-effectiveness after the first few years on the market.

Hilary Hutton-Squire says that Peter Clark, the chairman of the CDF, believes Yescarta is “a great candidate” for the CDF, and that Gilead agrees wholeheartedly with this view. That means if the two sides can resolve their differences on the data, Yescarta could get the green light for inclusion on the CDF within the next few months.

A second appraisal meeting is scheduled for 27 September, and NICE currently expects to finalise its decision by 19 December.

The CAR-T production process

DLBCL will be the competitive battleground for Novartis and Gilead, and there’s no doubt Yescarta has the upper hand at this early stage. It has significantly better response rates in DLBCL than Kymriah: its overall response rate (ORR) of 72% contrasts with 50% for Novartis’ drug.

However there are other factors at play that could influence which drug gains the upper hand. The most significant is the complexity CAR-T manufacturing process, and Novartis looks to have faltered on this score: it has already said it will focus first on its ALL patients in Europe because of a limited capacity to produce the armed T cells.

This could consolidate Gilead’s advantage in Europe – although payers across the continent will be keen for Novartis to enter the DLBCL fray in order to create price competition. In its favour, Novartis has a great deal of expertise in oncology marketing – where Gilead is a relative novice – and could make this count in any head-to-head battles.

Gilead is already in the lead in terms of revenues in the US market, largely because it gained FDA approval in the larger DLBCL market in October, with Novartis only adding DLBCL to its ALL licence in May this year.

Kymriah earned $16m in the second quarter, while Yescarta has reached $68m, ahead of consensus forecasts. Analysts predict Gilead’s drug could reach peak annual sales could exceed $2.5bn, well ahead of forecasts for Kymriah.

12th September 2018

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