Kymriah and Yescarta get positive NICE recommendation under managed entry agreement

On December 21st, Novartis’ Kymriah and Kite’s Yescarta have received NICE’s green light and are accessible to UK patients. These decisions come 3 months after initial negative draft guidances earlier this year. In the final guidances, NICE confirmed that the two CAR-Ts do not appear to meet the usual cost-effectiveness thresholds, mainly due to uncertainty on magnitude and duration of effect. Still, the two treatments are going to be reimbursed in the EMA approved indications. These positive decisions are possible thanks to a particular type of innovative access agreements, usually called Coverage with Evidence Development (CED) or conditional reimbursement and are a signal NICE bodies are taking new approaches in dealing with cell and gene therapies. Under these agreements, NICE and the relevant companies will collect evidence of effect of the two drugs over the next 3 to 5 years and will run new HTA assessments at the end of these periods. Access to Kymriah and Yescarta will be funded without restrictions through the UK Cancer Drugs Fund (CDF).

UK NICE says draft no to Novartis Kymriah in DBLCL

After the NICE draft no to Yescarta in DBLCL, NICE says draft no to Kymriah. The immediate question is: what is going on at NICE, are they going to deny access to CAR-Ts in DBLCL? The draft recommendation posted today provides NICE’s reasons for this no, and they are very similar to Yescarta’s:

  1. Lack of comparative evidence vs. standard of care
  2. Immature data, i.e. NICE’s experts would like to see longer follow-up data
  3. ICER above NICE threshold

The negative recommendations are only the first step in a process that will result in final decisions between December 2018 and January 2019.

What next? For Kymriah, we can expect some fine-tuning on the cost-effectiveness side. Certainly, there is no time for generating comparative data vs. standard of care and that will be challenging in any case. As NICE said, there is ‘no standard treatment for relapsed or refractory diffuse large B- cell lymphoma after 2 or more systemic therapies‘. Probably, Novartis will refine its work on indirect comparisons with chemotherapy. A few more months of follow up may also add to evidence that already looks strong to many experts.

Our expectations: despite the disappointing NICE Draft reccomendations, we are still positive on UK DBLCL patients’ chances to access CAR-Ts.

German G-BA starting Kymriah’s appraisal

A few days after Novartis announced Kymriah’s list price in Germany – i.e. 320’000 € – the G-BA has started the procedure to review the CAR-T for treating forms of child (ALL) and adult (DLBCL) leukemias. The G-BA review, that will be finalized in mid-December 2018,  will feed into price negotiations between Novartis and the German health insurances that will take place in 2019.

German G-BA positive on Takeda’s Darvadstrocel

The German G-BA just published the added-benefit assessment for Takeda/Tigenix’ Darvadstrocel, link to the G-BA webpage here: G-BA Darvadstrocel

Darvadstrocel has orphan drag status in Europe and therefore it is assumed by G-BA to bring some kind of benefit to patients. A consultation process will be held until the end of September and the final G-BA resolution with be published end of November 2018.

G-BA have assessed Darvadstrocel added benefit based on the pivotal trial ADMIRE-CD with the strongest evidence of effect coming from time-to-remission data both at 24 and 52 weeks.

UK NICE says draft No to Yescarta

Just the day after the good news of EMA marketing authorisation to Yescarta and Kymriah, NICE posted the Yescarta Draft Guidance for consultation, and it is a No. Here the link to the draft recommendation: NICE draft guidance

These news come as a surprise and apparently in contradiction with previous NICE work on CAR-Ts, the so-called CAR-T mock appraisal.

The NICE committee motivates this initial no with the lack of comparative data vs. chemotherapy and therefore on the uncertainty about size of benefit. Here below the excerpt from the NICE document:

“Evidence from a small, single-arm study suggests that people having axicabtagene ciloleucel have good response rates, overall survival and progression-free survival. But, there are no direct data comparing axicabtagene ciloleucel with salvage chemotherapy (referred to as best supportive care by the company). This means that the exact size of the benefit of axicabtagene ciloleucel compared with salvage chemotherapy is unknown.”


And now what?  – Yescarta’s draft guidance is currently undergoing a consultation process, and Gilead/Kite will have the opportunity to complement the submission with more relevant chemotherapy data. NICE has suggested to use subpopulation data from the ORCHARRD study or from the UK Haematological Malignancy Research Network. The NICE Committee will meet again on September 27th and a final decision is expected for December 17th.

Our guess: at NICE, an initial no does not mean no. There are good reasons to think that Gilead/Kite have the opportunity to turn it into a yes for Yescarta.