NICE first draft guidance rejects funding for venclyxto for CLL

This month, the National Institute for Health and Care Excellence (NICE) has released guidance on using AbbVie/Roche’s Venclyxto® (venetoclax) in the NHS in England, stating that they reject Venclyxto® for the treatment of CLL patients who have del(17p) or TP53 mutation and are unsuitable for, or progressed after, BCR pathway inhibitor treatment or whose disease progressed after both chemoimmunotherapy and a BCR pathway inhibitor.

The main reason for this rejection is that too many doubts and reservations were raised with venetoclax’s clinical evidence base, and so it not a cost-effective use of NHS resources.

Key Highlights:

• Evidence for venetoclax comes from phase I and phase II single-arm trials
  • Phase I M12-175 trial, 67 pts without del(17p) or TP53 mPFS = 41.4 months
  • Phase II M13-982 trial, 158 R/R CLL pts with del(17p) or TP53 mPFS = 27.2 months; after 1 yr, 86.5% pts were alive
  • Phase II M14-032 trial, recruited R/R CLL pts with del(17p) or TP53 mutation after BCR pathway inhibitor (ibrutinib, n = 43; idelalisib, n = 21). mPFS = not reached; after 1 yr, percentage of pts alive in the prior ibrutinib and prior idelalisib arms were 88.1% and 95.2%, respectively
• The committee had concerns that these trials enrolled relatively low numbers of patients; the results were based on intention-to-treat patient populations, so results are hard to relate to patient populations in clinical practice in England; and the single-arm design of these trials allows room for bias towards venetoclax
• No UK centers were included in the M12-175 or M14-032 studies, raising concerns with how generalizable the results of the trials are to clinical practice in England
• The trials recruited patients with ECOG PS <2 and so likely to have a lower burden of disease than patients in actual clinical practice in England, and so the treatment benefit of venetoclax for these patients is uncertain

The cost of the agent has also been a hurdle for NICE approval; 28 days of 400mg treatment (112-pack of 100mg tablets) costs £4,789.47 plus VAT.

Moreover, NICE made the decision that venetoclax should not be reimbursed by the new Cancer Drugs Fund (this makes drugs available for a short time so more conclusive clinical data and evidence can be collected).

NICE state that “This guidance is not intended to affect the position of patients whose treatment with venetoclax was started within the NHS before this guidance was published. Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop.”

On 8^th December 2016, the European Medicines Agency (EMA) granted Venclyxto® monotherapy conditional marketing authorization for the specific CLL indications mentioned above, and so is available in European countries. This decision was based on phase 2 data; but as it is conditional, the marketing authorization will be reviewed annually until late-stage data can be provided. Moreover, in April 2016, the US Food and Drug Administration (FDA) approved venetoclax, marketed as Venclexta®, for CLL patients the del(17p) and who have received at least one previous treatment.