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Takeda draws a cautious line under Iclusig

$100m buys an option over another third-gen drug, but Scemblix casts a long shadow.

Takeda has made a cautious bet to challenge Novartis’s chronic myelogenous leukaemia (CML) drug Scemblix, taking an option on a future licensing deal covering Ascentage Pharma’s similarly acting olverembatinib.

The move marks the Japanese group’s second attempt at becoming a significant player in CML, after it bought Ariad for an extraordinary $5.2bn in 2017; with Ariad came the CML drug Iclusig. But, despite Iclusig’s billing as a third-generation kinase inhibitor, that drug is now limited to a late-line CML setting, and with first and second-line CML studies terminated Takeda has evidently gone to Ascentage in the search for something better.

The olverembatinib deal seems rich too – an up-front fee of $100m only gives Takeda the rights to a future opt-in, whose formal exercise would presumably involve the Japanese group handing across an even larger chunk of cash. But then it does include key ex-China markets, including the US, Europe and Japan, for a product that already has regulatory approval.

That green light is in China, where olverembatinib is licensed to Innovent, and western approvals depend on the phase 3 Polaris-2 study, which only began last month. In the meantime, the CML space has been shaken up by Novartis, whose third-generation TKI Scemblix put up stellar data at ASCO, on the back of which it looks likely to have its label broadened from its currently approved third-line use to the front line.

Third-line CML

Olverembatinib’s Chinese approval is broadly similar to Scemblix’s current US label: CML patients in whom first and second-generation TKIs (for instance Novartis’s Gleevec and Tasigna respectively) have failed, and in chronic-phase CML carrying the T315I mutation.

This is backed by a registrational phase 2 study, whose data were presented at last year’s ASH conference. Here olverembatinib beat best available therapy on event-free survival, its primary endpoint, cutting risk of progression or death by 60%, and investigators highlighted the trial’s setting as representing the largest population of CML patients resistant to first as well as second-generation TKIs. 

That’s all very well, but the real battle here will be against the third-generation Scemblix, in the front-line setting – assuming that olverembatinib manages eventually to break into this.

For Iclusig, the drug Takeda acquired along with Ariad, first-line CML was already out of reach when that takeover closed in 2017, Ariad having terminated the Epic study four years earlier. Takeda then canned Iclusig’s second-line Optic-2L trial, leaving everything hanging on the third-line CML approval that finally came in the US four years ago.

By then Iclusig had become marginalised. Olverembatinib offers Takeda a second shot here, though between 2017 and now the treatment of CML has changed considerably, and it’s about to change further.


Selected BCR-ABL tyrosine kinase inhibitors for CML

DrugCompanyGenerationUS statusSupporting trials
GleevecNovartis1stApproved 1st lineNCT00006343
SprycelBristol Myers Squibb2ndApproved 1st lineDasision
TasignaNovartis2ndApproved 1st lineEnestnd
BosulifPfizer2ndApproved 1st line (but usually used later)Bfore
IclusigTakeda (ex Ariad)3rdApproved 3rd line; 1st-line Epic & 2nd-line Optic-2L trials terminatedOptic
ScemblixNovartis3rdApproved 3rd line; awaiting 1st-line approvalASC4first
OlverembatinibAscentage/ Innovent/ Takeda3rdPhase 3 2nd-line trial started May 2024 (approved 3rd line in China)Polaris-2

Source: OncologyPipeline.


Molecular Drug Targets