Pfizer’s glasdegib has become the first SMO inhibitor to show a benefit in two haematological malignancies, boosting overall survival in a phase II trial.
Glasdegib (previously known as PF-04449913) extended overall survival in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) to almost nine months when added to low-dose cytarabine therapy, compared to 4.9 months with cytarabine alone.
The trial involved patients ineligible for intensive chemotherapy, and was presented at the American Society of Hematology (ASH) meeting in San Diego.
There are already two SMO (smoothened) inhibitors on the market – Novartis’ Odomzo (sonidegib) and Roche’s Erivedge (vismodegib) – and both are approved to treat a form of skin cancer known as basal cell carcinoma in patients not suitable for surgery or radiotherapy.
That indication represents a small patient population, and extending the use of SMO inhibitors – which target the hedgehog (Hh) pathway – into new indications such as blood cancers could significantly increase the earnings potential of the new class. Sales of Erivedge were around $150m in the first nine months of the year, while Odomzo has not yet grown enough for Novartis to break out its quarterly sales figures.
In contrast, analysts at Credit Suisse have predicted that approval in AML could make glasdegib a $450m product in 2020, with an additional upside if it can claim approvals in other indications such as MDS, acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML) and solid tumours.
“The Hh pathway is a compelling target in cancer research because of the ability to target and disrupt the root of the cancer, that is the cancer-originating cell,” said Jorge Cortes, University of Texas, MD Anderson Cancer Center.
“As the first SMO inhibitor to demonstrate clinical benefit in patients with AML and high-risk MDS … these results with glasdegib provide hope that interfering with this pathway may lead to potential new treatment options for blood cancers that may improve patient outcomes.”
Other SMO inhibitors are also coming through development meanwhile, notably Exelixis/Bristol-Myers Squibb’s BMS 833923 – in phase II testing for CML – and Ignyta/ Eli Lilly’s taladegib which is in a phase I/II trial in small cell lung cancer (SCLC) patients.