IN THE PIPELINE
FDA Update: Recent Approvals and Designations for
Orphan Drugs
In instances where an investigational drug would be the
first available treatment or would have advantages over
existing treatments, the U.S. Food and Drug Administration (FDA) can accelerate the progress of a drug’s approval
through its “breakthrough therapy” and “orphan drug”
designations.
Breakthrough therapy designation, established by the
FDA’s Safety and Innovation Act of 2012, applies to an
investigational or approved drug that is intended to treat
a serious or life-threatening disease or that may demonstrate substantial improvement over existing therapies.
The FDA will expedite the development and review of
these drugs within 60 days of receipt.
The Orphan Drug Act of 1983 provides special status
to an FDA-approved drug or biologic product that treats
a rare disease or condition affecting fewer than 200,000
Americans. Orphan drug status can also be given to a
product that treats a disease affecting more than 200,000
people, but only in cases in which the manufacturer is not
expected to recover the costs of development and marketing the product. With orphan drug designation, the drug’s
sponsor is provided various development incentives,
including tax credits for qualified clinical testing.
Below is a list of agents that were recently granted
breakthrough designation or were approved as orphan
therapies.
Complications of Hematopoietic Cell Transplantation
Ruxolitinib: The JAK1 and JAK2 inhibitor ruxolitinib received
breakthrough therapy designation for the treatment of patients
with acute graft-versus-host disease (aGVHD), a condition
that has no approved treatments specific to the disease. Its
approval was based on results from a retrospective analysis of
patients who developed corticosteroid-refractory aGVHD or
chronic GVHD (cGVHD) following allogeneic hematopoietic
cell transplantation (HCT) for a hematologic malignancy. The
overall response rate (ORR) was 81.5 percent (n=44) in the
aGVHD group and 85.4 percent (n=35) in the cGVHD cohort,
with a median time to response of 1.5 weeks and three weeks,
respectively. Ruxolitinib is also approved for the treatment of
myelofibrosis and polycythemia vera.
Ibrutinib: The tyrosine kinase inhibitor ibrutinib received
breakthrough therapy and orphan drug designation for the
treatment of patients with cGVHD after failure of one or
more lines of systemic therapy. The FDA’s decision was based
on data from a phase Ib/II study of patients with steroiddependent or refractory cGVHD who received single-agent
ibrutinib. The ORR (defined as reduction in cGVHD per
National Institutes of Health Consensus Response Criteria)
was 55 percent. Ibrutinib is also approved for the treatment
of Waldenström macroglobulinemia and previously treated
chronic lymphocytic leukemia and mantle cell lymphoma.
Defibrotide sodium: The FDA granted approval and orphan
drug status for defibrotide sodium for adults and children with
hepatic veno-occlusive disease (VOD) with additional kidney
or lung abnormalities after receiving HCT – making it the first
FDA-approved treatment for severe hepatic VOD. The approval
was based on the results of three studies that showed 38 to 45
percent of patients treated with defibrotide sodium were alive
at 100 days post-HCT. Patients with bleeding complications
or those taking blood thinners or other medications to reduce
blood clots should not receive defibrotide sodium.
Clotting and Bleeding Disorders
Plasminogen therapy: The FDA granted “Fast Track” designation to a plasminogen drug candidate for the treatment of
patients with congenital plasminogen deficiency. The investigational plasminogen therapy is composed of a naturally
occurring protein that is synthesized by the liver and circulates
in the blood. The drug is being investigated in a phase II/III
clinical trial of patients with congenital plasminogen deficiency, where it has demonstrated a rapid response in lesion
resolution and decreased the need for surgery.
Coagulation factor IX (recombinant), albumin fusion
protein (albutrepenonacog alfa): The FDA approved
albutrepenonacog alfa for use in children and adults with
hemophilia B for on-demand control and prevention of
bleeding episodes, the management of peri-operative bleeding,
and as routine prophylaxis to reduce the frequency of bleeding
episodes. This is the first coagulation factor–albumin fusion
protein product and the second factor IX fusion protein
product to be approved in the United States.
Kovaltry™ antihemophilic factor (recombinant): Kovaltry™
antihemophilic factor (recombinant) – an unmodified, fulllength factor VIII compound – was granted orphan drug designation for the treatment of hemophilia A in children and adults.
The approval was based on results from three multicenter,
open-label, uncontrolled studies, in which the drug demonstrated control of and protection from bleeds when used prophylactically two to three times per week.
Leukemia
CPX-351: The FDA granted breakthrough therapy designation
October 2016
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