Novartis gets FDA okay for frontline use of Scemblix in CML

Novartis has picked up a new FDA approval for its chronic myeloid leukaemia therapy Scemblix that it believes is critical to unlocking the drug's blockbuster sales potential.

First-in-class STAMP inhibitor Scemblix (asciminib) is already starting to see sales ramp up as a third-line or later therapy for CML – an indication approved by the FDA in 2021 – with a third-quarter tally up 72% to $182 million.

The new accelerated approval covers the use of Scemblix for newly diagnosed patients with Philadelphia chromosome-positive CML in the chronic phase (Ph+ CML-CP), which Novartis said expands the eligible population for the drug by around four times.

It comes on the back of the ASC4FIRST trial – reported at this year's ASCO congress – which suggested the drug could offer a safer and more effective alternative to existing tyrosine kinase inhibitors (TKIs) for this type of CML and looks set to be practice-changing.

Current treatment relies on first-generation TKI imatinib – now available generically – as well as second-generation drugs like Bristol-Myers Squibb's Sprycel (dasatinib), Novartis' Tasigna (nilotinib), and Pfizer's Bosulif (bosutinib).

In ASC4FIRST, 68% of patients treated with Scemblix had a major molecular response (MMR) after 48 weeks, compared to 49% in patients treated with TKIs, with the more stringent criteria of a deep molecular response (DMR) achieved in 39% and 21% of patients, respectively.

Novartis also believes Scemblix offers a favourable safety and tolerability profile compared to current drugs, with fewer adverse events, treatment interruptions, and discontinuations seen with its drug in the study.

Despite the dramatic impact that TKIs have had in CML – including a tripling in the five-year survival rate to around 70% - almost half of patients still have to change therapy within two years due to side effects or the development of drug resistance.

The new approval has been welcomed by chief executive of The Leukaemia & Lymphoma Society, Lee Greenberger, who stressed the importance of patients "finding a medicine that's right for them at the very beginning of treatment", which "may lead to better long-term disease control with fewer side effects."

Accelerated approval means that Novartis will have to provide further clinical evidence for Scemblix's value as a first-line treatment for Ph+ CML-CP. The ASC4FIRST trial remains ongoing, with the next scheduled analysis at week 96, while another phase 2 trial called the ASC2ESCALATE study, in patients who have been treated with one TKI, will also add to the dataset.

Novartis has previously suggested that Scemblix could become a $3 billion-a-year product. In its third-quarter results update earlier this week, the company said it was "fully prepared to obtain rapid market access to really ensure a rapid launch in the US and eventually around the world."

China and Japan submissions have already been completed, said Novartis CEO Vas Narasimhan, who added that the company is also on track for a European submission in 2025.