According to a recent announcement by AstraZeneca, the U.S. FDA granted its approval for Koselugo (selumetinib). This is the first drug to be approved for the treatment of children with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). PNs occur inside nerve sheaths in the form of bulging masses in skin folds and connective tissue.
The Phase II SPRINT Trial
The approval was based on the Phase II SPRINT Stratum 1 trial that showed selumetinib reduced inoperable tumors, reduced pain, improved function, and improved overall quality of the children’s lives after treatment.
A total of fifty patients participated in the Phase II trial. Researchers assessed outcomes according to each individual patient’s tumor-related symptoms. This approach had not been used in previous NF1 clinical trials.
Results
The Overall Response Rate (ORR) was defined as a percentage of patients who experienced a complete response or experienced a minimum of twenty percent reduction in PN (inoperable tumor) volume.
ORR for the Phase II trial was sixty-six percent (partial response) with eighty-two percent of these patients maintaining the response for one year or more. No patients had their tumors completely disappear.
About Koselugo (selumetinib)
Koselugo, a kinase inhibitor, blocks critical protein kinase enzymes, thus preventing the growth of tumor cells.
The drug has been developed and approved specifically for patients with inoperable plexiform neurofibromas (PN). These tumors can be found in many areas of the body such as extremities, face, around the spine, or deep within the body.
A total of fifty patients participated in the Phase II trial. Researchers assessed outcomes according to each individual patient’s tumor-related symptoms. This approach had not been used in previous NF1 clinical trials.
Adverse Responses to Selumetinib
The most common side effects to the drug include vomiting, diarrhea, abdominal pain, rash, fever, musculoskeletal pain, and fatigue.
Patients may also experience inflammation of the mouth and lips (stomatitis), infections of the skin surrounding toe or fingernails (paronychia) and itching.
More serious side effects may involve heart failure or ocular toxicity, which is acute and chronic damage to the eye.
Researchers discovered during animal studies of selumetinib that the drug may have harmful effects on newborn babies if it is given to pregnant women.
About FN1-PN
NF1 affects approximately one out of every three thousand infants. About thirty to fifty percent of NF1 patients experience PN tumors.
PNs may cause symptoms such as motor, airway, bladder, or bowel dysfunction, as well as possible disfigurement.
FDA Designations
The FDA granted AstraZeneca Pharmaceuticals the Rare Pediatric Disease designation for treatment of pediatric NF1.
About AstraZeneca
AstraZeneca Pharmaceuticals LP is a global biopharmaceutical company. It is based in Cambridge, UK and operates in over 100 countries. Its medicines are used by millions of patients worldwide. The company’s focus is on three main therapy areas: oncology, cardiovascular & metabolic disease. AstraZeneca also works with biotech research institutions on emerging technologies such as modified RNA and CRISPR genome editing.
