Better than Pfizer bosutinib Novartic Leukemia Oral Therapy Phase 3 clinical reached the main endpoint.

Novarca announced on August 26th that its research therapy asciminib (ABL001) had a statistically significant advantage over Pfizer bosutinib (BOSULIF®) in treating patients with chronic stage-stage Philadelphia chromosomal-positive chronic granulocytic leukemia (PH-CML-CP) at a statistically significant level, and that the initial analysis of phase 3 clinical studies had reached the primary endpoint of ASCEMBL.
gives Novardic more hope of winning approval for a new drug to address drug resistance and inability to treat chronic granulocytic leukemia (CML) multiline therapy.
ASCEMBL is a multi-center, open-label, randomized Phase 3 clinical study designed to compare the therapeutic effects of oral therapy asciminib and bosutinib on adult patients with chronic Ph-CML-CP.
study recruited 234 CML patients who had been treated with two or more tyrosine kinase inhibitors (TKIs), including those who had recently failed or were not acceptable to TKI treatment.
randomly divided the patient into asciminib or bosutinib once a day orally.
at 24 weeks, the researchers assessed how much the number of BCR-ABL genes in a patient's blood declined to define MMR.
did not share more specific data, but plans to submit the trial data to an upcoming medical conference and drug regulators, which the FDA has granted asciminib fast-track eligibility.
, Novart's chief executive, Vas Narasimhan, said he expected to file a drug approval application in the first quarter of 2021.
Currently, doctors treating patients with Ph-CML-CP can choose from competing drugs at Novargo's Gleevec and Tasigna, as well as BMS and Pfizer, and most patients survive 10 years of treatment, but disease progress is still an unavoidable risk.
that while patients who develop resistance to the original treatment may switch to another TKI, many approved therapies target the same ATP binding bits on ABL1 kinases.
similarity between these therapies means that mutations in one region of kinase can invalidate multiple drugs.
more hope that Novartic's research and development of asciminib will fill the gaps in the current treatment pathway.
Asciminib is an other inhibitor combined with the nutmeg bits of the BCR-ABL1 protein.
BCR-ABL is a fusion gene formed by the cancer gene c-ABL on chromosome 9 and the break point cluster cluster of chromosome 22.
the formation of BCR-ABL causes abnormal cell proliferation by keeping the corresponding tyrosine kinase active, which is an important target for the treatment of CML.
since the first small-molecule drug, imatinib, which targets BCR-ABL, was launched in 2001, more than a dozen mutations, such as T315I, have been found to occur at its targets and become resistant.
second-generation inhibitors dasatinib and nilotinib are better and effective for most mutations, but still not for T315I mutations.
next-generation BCR-ABL inhibitor bosutinib is still ineffective against T315I mutations and causes new mutations.
Asciminib is different from the currently approved ABL1 kinase inhibitor in that it does not bind to the ATP binding point of the kinase, but acts as an other inhibitor, combined with an empty pocket of a bit in the kinase domain, which is normally occupied by the ABL1 nutmeg-encumerated N-end (see figure below).
by binding nutmeg to the acetylene bit, the drug can simulate the role of nutmeg salts and restore inhibition of kinase activity.
Because of the unique composition of nutmeg pockets, asciminib is highly selective to ABL1 (and presumably to ABL2 kinases) and targets both natural and mutant BCR-ABL1, including T315I mutants.
combination of
asciminib and BCR-ABL1 nutmeg endpoints Previous studies have shown that asciminib is active in CML patients who have previously been resistant to TKIs or have had unacceptable side effects and who have received extensive treatment, including those with failed ponatinib treatment and T315I mutations.
addition, asciminib combined with imatinib has shown promising initial efficacy and good safety and tolerance in patients with CML who have previously received 2 or more TKIs treatments.
first half of this year, Novart's Tasigna achieved sales of nearly $1 billion, while Grexit earned $617 million.
Bosulif also reported sales of $213 million in the first half of the year, up 20 percent from the same period in 2019.
data show that the market demand for CML is still not being met.
is currently conducting several clinical trials in the hope of helping patients with multi-line treatment across CML.
if Novaral were to launch the drug as an advantageous first-line treatment option, business opportunities would increase significantly.
source: 1.Asciminib in Chronic Myeloid Leukemia after ABL Kinase Reseed Fail 2.Novartis' asciminib bests Pfizer's Bosulif in phase 3 leukemia trial 3.Novartis investigational 3 leukemia trial 3.Novartis investigational 3 COURSE resed or asciminib (ABLBL001) meetss primary endpoint to my