Stivarga receives expanded approval to include hepatocellular carcinoma
WASHINGTON — The Food and Drug Administration on Thursday expanded the approved use of Stivarga (regorafinib) to include treatment of patients with hepatocellular carcinoma (HCC or liver cancer) who have been previously treated with the drug sorafenib. The drug, manufactured by Bayer HealthCare Pharmaceuticals, is the first FDA-approved treatment for a liver cancer in almost a decade.
“Limited treatment options are available for patients with liver cancer,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “This is the first time patients with HCC have had an FDA-approved treatment that can be used if their cancer has stopped responding to initial treatment with sorafenib.”
According to the National Cancer Institute, approximately 40,710 people will be diagnosed with liver cancers in 2017 and approximately 28,920 will die of these diseases. HCC originates in the liver and is the most common form of liver cancer.
Stivarga is a kinase inhibitor that works by blocking several enzymes that promote cancer growth, including enzymes in the vascular endothelial growth factor pathway. Stivarga is also approved to treat colorectal cancer and gastrointestinal stromal tumors that are no longer responding to previous treatments.
The safety and efficacy of Stivarga for treatment of HCC were studied in a randomized trial of 573 patients with HCC whose tumors had progressed after receiving sorafenib. The trial measured the length of time the patients lived after receiving treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival) and the percent of patients whose tumors completely or partially shrank after treatment (overall response rate). The median overall survival for patients taking Stivarga was 10.6 months, compared to 7.8 months for patients taking a placebo. The median progression-free survival for patients taking Stivarga was 3.1 months compared to 1.5 months for patients taking a placebo. The overall response rate for patients taking Stivarga was 11 percent, compared to 4 percent of patients taking placebo.
Common side effects of Stivarga include pain (including gastrointestinal and abdominal pain), hand-foot skin reaction, fatigue, diarrhea, decreased appetite, high blood pressure (hypertension), infection, difficulty speaking (dysphonia), high levels of bilirubin in the blood (hyperbilirubinemia), fever, inflammation of the mucous membranes (mucositis), weight loss, rash and nausea. Stivarga is associated with serious risks, including liver damage (hepatotoxicity), infections, heavy bleeding (hemorrhage), holes in the stomach or intestines (gastrointestinal perforation or fistula), skin damage (dermatologic toxicity), hypertension, problems with blood flow to the heart (cardiac ischemia and infarction), temporary brain swelling(reversible posterior leukoencephalopathy syndrome) and wound healing complications.
FDA approves first drug for specific form of Batten disease
WASHINGTON — The Food and Drug Administration on Thursday approved Brineura (cerliponase alfa) as a treatment for a specific form of Batten disease. BioMarin Pharmaceuticals’ Brineura is the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency.
“The FDA is committed to approving new and innovative therapies for patients with rare diseases, particularly where there are no approved treatment options,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research. “Approving the first drug for the treatment of this form of Batten disease is an important advance for patients suffering with this condition.”
CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses, collectively referred to as Batten disease. CLN2 disease is a rare inherited disorder that primarily affects the nervous system. In the late infantile form of the disease, signs and symptoms typically begin between ages 2 and 4. The initial symptoms usually include language delay, recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects essential motor skills, such as sitting and walking. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens. Batten disease is relatively rare, occurring in an estimated two to four of every 100,000 live births in the United States.
The efficacy of Brineura was established in a non-randomized, single-arm dose escalation clinical study in 22 symptomatic pediatric patients with CLN2 disease and compared to 42 untreated patients with CLN2 disease from a natural history cohort (an independent historical control group) who were at least 3 years old and had motor or language symptoms. Taking into account age, baseline walking ability and genotype, Brineura-treated patients demonstrated fewer declines in walking ability compared to untreated patients in the natural history cohort.
The safety of Brineura was evaluated in 24 patients with CLN2 disease aged 3 to 8 years who received at least one dose of Brineura in clinical studies. The safety and effectiveness of Brineura have not been established in patients less than 3 years of age.
The most common adverse reactions in patients treated with Brineura include fever, ECG abnormalities including slow heart rate (bradycardia), hypersensitivity, decrease or increase in CSF protein, vomiting, seizures, hematoma (abnormal collection of blood outside of a blood vessel), headache, irritability, increased CSF white blood cell count (pleocytosis), device-related infection, feeling jittery and low blood pressure.
Branded thiotepa shipped by Amneal
PATERSON, N.J. — Amneal Biosciences, the exclusive U.S. distributor for Tepadina, on Thursday began shipping the branded thiotepa. The product is available for purchase through major wholesalers and distributors.
Tepadina is approved to reduce the risk of graft rejection when used in conjunction with high-dose busulfan and cyclophosphamide as a preparative regimen for allogeneic hematopoietic progenitor (stem) cell transplantation (HSCT) for pediatric patients with class 3 beta-thalassemia. In addition, the product is approved for the same oncologic indications as generic thiotepa.
"The introduction of 100 mg thiotepa provides pharmacists with a convenient choice of sizes to accommodate larger doses," explains Amneal Biosciences President, Charles Lucarelli. "We are thrilled to bring to the U.S. a product that is not only valuable to the pediatric transplant process, but in the 100 mg vial that's been unavailable for years. Now we have a fully FDA-approved thiotepa molecule with options for the reconstituting pharmacist."
According to Amneal, Tepadina may cause severe marrow suppression, and high doses may cause marrow ablation with resulting infection or bleeding. Hematopoietic progenitor (stem) cell transplantation (HSCT) is required to prevent potentially fatal complications of the prolonged myelosuppression after high doses of Tepadina. Tepadina should be considered potentially carcinogenic in humans. It is contraindicated in patients with severe hypersensitivity to thiotepa and in concomitant use with live or attenuated vaccines. The most common adverse reactions are neutropenia, anemia, thrombocytopenia, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated bilirubin, mucositis, cytomegalovirus infection, hemorrhage, diarrhea, hematuria and rash.
Amneal Biosciences brings Tepadina to the U.S. market on behalf of NDA-holder Adienne SA. "This exclusive distribution partnership with Adienne further demonstrates Amneal's ability to successfully commercialize complex products in the U.S.," said Amneal VP of Global Strategy and Corporate Development, Apurva Saraf. "We continue to pursue such strategic partnerships to complement our expansive and diverse internal pipeline."