- The Food and Drug Administration on Friday approved Novartis' Adakveo to prevent blood-vessel blockages in patients with sickle cell anemia that can be painful and sometimes fatal.
- Adakveo's OK comes on the heels of the 2017 approval of Emmaus Medical's Endari, the first new sickle cell drug in 20 years. Several experimental drugs, including a gene therapy, are nearing market.
- Adakveo works by targeting a protein that can make misshapen red blood cells and blood vessels sticky, thereby preventing the blockages that can result in painful "vaso-occlusive crises."
Adakveo (crizanlizumab) is one of two sickle-cell treatments that could launch within months of each other, and they may not necessarily be direct competitors. Global Blood Therapeutics has submitted an FDA application for voxelotor, which works by improving oxygen absorption by red blood cells, and a decision is due by Feb. 26, 2020.
Novartis' treatment is an antibody that blocks the action of a protein called P-selectin, which can cause blood cells to stick to each other and cells in blood vessel walls. The sticking can in turn trigger a vaso-occlusive crisis, which may cause pain and lead to costly hospitalizations, or even death.
"Every VOC can be debilitating and lead to hospitalization, organ damage or even death," said Andrew Cavey, global program head at Novartis Oncology, in an interview. (Organizationally, Adakveo is grouped with Novartis' other hematology medicines, most of which are in cancer.)
"Every VOC can lead to hospitalization — 200,000 ER visits a year in the U.S. are due to VOCs, so there's a significant cost component as well."
Data from a trial named SUSTAIN supported approval, showing Adakveo reduced the number of pain crises leading to a healthcare visit by about one per year compared to placebo. While Novartis chose to focus only on more severe VOCs in SUSTAIN, it will be testing Adakveo's effect on VOCs that don't result in hospitalization in subsequent studies.
The drug also reduced the average number of days patients were in the hospital by 42%, and more patients taking Adakveo had no vaso-occlusive crises — 36% versus 17% taking a placebo. The median time from initiating treatment to the first crisis was 4.1 months for Adakveo patients compared with 1.4 months for placebo patients.
Adakveo is a once-monthly infusion, which could make it a less attractive treatment when compared with voxelotor, an oral drug. However, Cantor Fitzgerald analyst Elemer Piros wrote in a July note that the two might be viewed as complementary therapies "given both drugs show beneficial results in different measures, and work through different mechanism of actions."
Novartis priced Adakveo, which is dosed by weight, at a wholesale acquisition cost of $2,357 per vial. Most patients would take between 3 and 4 vials per month, Novartis said, making the monthly list price between $7,000 and $9,500. The drug will be available in the coming weeks.
Adakveo could end up the first in a wave of new sickle cell disease drugs.
Bluebird Bio has in late-stage clinical trials a gene therapy candidate similar to its new product Zynteglo, which has been approved for the related disorder beta thalassemia.
And in addition to voxelotor, Global Blood Therapeutics has licensed a pre-clinical P-selectin inhibitor from Roche called inclacumab.
Sickle cell disease affects 100,000 Americans, and is more common in people of African, Mediterranean and Middle Eastern descent.
Ned Pagliarulo contributed reporting.