CHICAGO — Novartis said its chronic myeloid leukemia drug Scemblix was better than its own first-generation blockbuster medicine and an investigator’s choice of second-generation treatments made by itself, Bristol Myers Squibb and Pfizer.
Jeff LegosThe detailed Phase 3 results presented Friday could potentially open up Scemblix to at least twice as many patients, Novartis’ global head of oncology Jeff Legos said in an interview with Endpoints News. The results were presented at the American Society of Clinical Oncology meeting.
In the nearly 400-patient trial, Scemblix performed better than existing therapies on a key measure of disease control — major molecular response — than existing therapies. The wins set up Scemblix for a potential expansion from third-line use to first-line in people with Philadelphia chromosome-positive chronic myeloid leukemia, or Ph+ CML-CP.
Scemblix is approved in more than 70 countries, including in the US as of 2021. Data from the trial, called ASC4FIRST, are under review at the FDA, Novartis said in a press release. The drug has a breakthrough therapy designation from the agency in the first-line setting.
Novartis has been in the CML space for decades, with the first-generation tyrosine kinase inhibitor Gleevec and a second-generation drug called Tasigna. Bristol Myers’ Sprycel and Pfizer’s Bosulif are also part of the second-generation class of TKIs for CML.
But many patients with CML, a chronic disease, still don’t fully benefit from the TKI inhibitors, Legos said, calling the disease “unsolved.”
“Despite the advent and innovation from the Gleevec days all the way to the Tasigna days, unfortunately about 50% of patients fail to meet their major molecular response treatment goals,” Legos said. “About 25% of patients actually switch TKIs in their first year because of challenges with safety and tolerability.”
In the ASC4FIRST trial, Novartis tested whether Scemblix was better than an investigator’s choice among Gleevec, Tasigna, Sprycel and Bosulif, or Gleevec alone, on major molecular response rate, or MMR.
At week 48, Scemblix outperformed both groups. The MMR rate for patients on Scemblix was 67.7% versus 49% for those on the investigator-selected standard of care. The rate was 69.3% for patients on Scemblix versus 40.2% for those who took Gleevec alone. The results were statistically significant.
In January, Novartis said in a press release that the trial had been a success, but didn’t share detailed data.
In a preview note, Jefferies analysts had predicted a “best case” as MMR being greater than 60% for Scemblix. Analysts at the firm said the drug could reach $4.5 billion in worldwide peak sales, near the $4.7 billion height of Gleevec in the 2010s. The drug had net sales of $413 million in 2023, a 177% increase from $149 million in all of 2022.
Oreofe Odejide“This is really poised to potentially change the management, first-line treatment of chronic myeloid leukemia,” Oreofe Odejide, a medical oncologist at Dana-Farber Cancer Institute and assistant professor at Harvard, told reporters during a virtual press briefing.
Novartis also said fewer patients stopped taking Scemblix due to adverse events than patients on the other drugs. For the Scemblix group, the rate of adverse events leading to treatment discontinuation was 5%. The rates were about double for Gleevec alone (11%) and investigator’s choice of the second-generation TKIs (10%).
The rate of grade 3 or higher adverse events was 38% for Scemblix, 44% for Gleevec alone and 55% for the second-generation TKIs, Novartis said.
The lower rate of toxicity is “really terrific,” ASCO’s chief medical officer Julie Gralow said during a press briefing. “Especially in this group of patients who, for the most part, can live a long time but are on treatment for life.”