FDA approved Cyramza (ramucirumab) to treat patients with advanced stomach cancer or gastroesophageal junction adenocarcinoma.
Cyramza is an angiogenesis inhibitor that blocks the blood supply to tumors. It is intended for unresectable or metastatic cancers that have been treated with a fluoropyrimidine- or platinum-containing therapy.
Cyramza’s safety and effectiveness were evaluated in a clinical trial of 355 participants with unresectable or metastatic stomach or gastroesophageal junction cancer. Two-thirds of trial participants received Cyramza while the remaining participants received a placebo.
Results showed participants treated with Cyramza experienced a median overall survival of 5.2 months compared to 3.8 months in participants receiving placebo.
Additionally, participants who took Cyramza experienced a delay in tumor growth compared to participants who were given placebo. Results from a second clinical trial that evaluated the efficacy of Cyramza plus paclitaxel versus paclitaxel alone also showed an improvement in overall survival.
The FDA reviewed Cyramza, marketed by Eli Lilly, under its priority review program and was also granted orphan product designation.
FDA granted accelerated approval to Zykadia (ceritinib) for patients with a certain type of metastatic non-small cell lung cancer.
Zykadia is the fourth drug with breakthrough therapy designation to receive FDA approval. It is being approved four months ahead of the product’s goal date of Aug. 24. The FDA had also granted Zykadia priority review and orphan product designations.
Zykadia is an anaplastic lymphoma kinase tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients with metastatic ALK-positive NSCLC who were previously treated with crizotinib, the only other approved ALK tyrosine kinase inhibitor. Only 2 to 7 percent of patients with NSCLC are ALK-positive.
Zykadia’s safety and effectiveness were established in a clinical trial of 163 participants with metastatic ALK-positive NSCLC. All participants were treated with Zykadia. Results showed that about half of the participants had their tumors shrink, and this effect lasted an average of about seven months.
Common side effects of Zykadia include gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Laboratory abnormalities such as increased liver enzymes, pancreatic enzymes and increased glucose levels were also observed.
Zykadia is marketed by Novartis. The FDA’s accelerated approval program allows approval of a drug to treat a serious disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising drugs while the company conducts confirmatory clinical trials.
FDA approved the cobas HPV test for women 25 and older that can be used alone to help a health care professional assess the need for a woman to undergo additional diagnostic testing for cervical cancer. The test also can provide information about the patient’s risk for developing cervical cancer in the future.
Using a sample of cervical cells, the test detects DNA from 14 high-risk HPV types. The test specifically identifies HPV 16 and HPV 18, while concurrently detecting 12 other types of high-risk HPVs.
Based on results of the cobas HPV Test, women who test positive for HPV 16 or HPV 18 should have a colposcopy. Women testing positive for one or more of the 12 other high-risk HPV types should have a Pap test to determine the need for a colposcopy. Health care professionals should use the cobas HPV Test results together with other information, such as the patient screening history and risk factors, and current professional guidelines.
The FDA first approved the test in 2011 for use in conjunction with or as a follow-up to a Pap test (cell cytology), which examines cervical cells for changes that might become cervical cancer. This approval expands the use of the test to include use as either a co-test or as a primary cervical cancer screening test, however; it does not change current medical practice guidelines for cervical cancer screening.
Data supporting the use of the cobas HPV Test as a primary screening test for cervical cancer included a study of more than 40,000 women 25 years and older undergoing routine cervical exams. Women who had a positive Pap test or whose cervical cells screened positive for HPV, as well as a subset of women whose Pap and HPV tests were both negative, underwent a colposcopy and cervical tissue biopsy. All biopsy results were compared to the Pap and cobas HPV Test results. The cobas HPV Test is manufactured by Roche Molecular Systems Inc.
FDA approved Lipiodol for selective hepatic intra-arterial use for imaging tumors in adults with known hepatocellular carcinoma.
This approval was received shortly after FDA granted approval to a new site to manufacture Lipiodol, validated for US distribution only (Jubilant HollisterStier, Canada). Lipiodol received an orphan-drug designation for management of patients with known HCC in October 2013.
Guerbet, Lipiodol’s sponsor, plans to transition from the temporary importation program as soon as product from the newly approved manufacturing plant will be available in the U.S. Lipiodol is indicated for hysterosalpingography in adults, and lymphography in adults and children, and is approved for use in over 47 countries.
It is the only oil-based iodinated contrast medium for radiology, launched in France in 1921. It is estimated that more than 200 million of Lipiodol doses have been administered worldwide. The contrast agent was first launched in the U.S. in 1954 and marketed as Ethiodol.
FDA approved a supplemental biologic license application for the use of Arzerra (ofatumumab), a CD20-directed cytolytic monoclonal antibody, in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukemia for whom fludarabine-based therapy is considered inappropriate.
The approval of the first-line indication is based on results from a phase III study, COMPLEMENT 1, which demonstrated statistically significant improvement in median progression-free survival in patients who received the combination of Arzerra and chlorambucil compared to patients who received chlorambucil alone.
The results from COMPLEMENT 1, the randomized, open-label, parallel-arm, pivotal Phase III study evaluating the combination of Arzerra and chlorambucil (n=221) versus chlorambucil alone (n=226) demonstrated statistically significant improvement in median PFS in patients randomized to Arzerra and chlorambucil compared to patients randomized to chlorambucil alone (22.4 months versus 13.1 months, respectively) (HR=0.57 [95% CI, 0.45, 0.72] p < 0.001). Arzerra is sponsored by GlaxoSmithKline and Genmab A/S.
FDA and the European Commission have granted orphan drug designation to volasertib for acute myeloid leukemia.
Volasertib is currently being evaluated in a phase III clinical trial for the treatment of patients aged 65 or older with previously untreated AML who are ineligible for intensive remission induction therapy.
Volasertib has not been approved by the FDA or EC regulatory authorities; its safety and efficacy have not been established. Volasertib is an investigational compound that inhibits Polo-like kinase. Plk1 is the best characterized kinase of the Plk family, and regulates cell division.
In both the U.S. and EU, orphan drug designation is a status given to investigational compounds intended to treat a rare disease or condition that has limited treatment options. To qualify for FDA’s orphan drug designation, the drug must, among other requirements, address a disease that affects fewer than 200,000 total people in the U.S. The European Medicines Agency defines a rare disease as one affecting no more than five people per 10,000 in the EU.
Following the breakthrough therapy designation granted by the FDA in 2013, Boehringer Ingelheim, the drug’s sponsor, is continuing to expedite the development of volasertib as a potential treatment option. Publication of the phase I/II trial data that was used in support of the breakthrough therapy designation is expected later this year.
The Committee for Medicinal Products for Human Use of the European Medicines Agency has issued a positive opinion recommending marketing authorization for Mekinist (trametinib) as a single agent in the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
Mekinist is a MEK inhibitor that targets the MAPK pathway, which regulates the normal growth and death of cells, and plays a role in metastatic melanoma development.
Mekinist as a single agent has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy. Before taking Mekinist, patients must have confirmation of BRAF V600 mutation using a validated test.
The CHMP recommendation for Mekinist monotherapy is based on a randomized open label phase III study comparing Mekinist to chemotherapy in 322 patients with BRAF mutant melanoma (V600E and V600K) and a non-randomized phase II study in 97 patients with BRAF mutant melanoma split in two cohorts: previously treated or not treated with a BRAF inhibitor.
A CHMP positive opinion is one of the final steps before marketing authorization is granted by the European Commission, but does not always result in marketing authorization. A final decision by the EC is anticipated during the second quarter of 2014.
Mekinist is approved as a single agent and in combination with Tafinlar (dabrafenib) in the U.S. and Australia. It is also approved as monotherapy in Canada. Mekinist was in-licensed by GlaxoSmithKline in 2006.
Based on data from a phase III head-to-head comparison of single agent Imbruvica (ibrutinib) versus ofatumumab in chronic lymphocytic leukemia and small lymphocytic lymphoma, Pharmacyclics Inc. submitted a supplemental new drug application to the FDA. Imbruvica is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech Inc.
The RESONATE study, PCYC-1112, enrolled 391 patients with CLL or SLL who had received at least one prior therapy. At a planned interim analysis in January 2014, the results of the RESONATE study demonstrated a statistically significant improvement in progression-free survival in patients treated with Imbruvica. Patients in the Imbruvica arm also showed a statistically significant improvement in overall survival.
Data from this study will be presented at the American Society of Clinical Oncology annual meeting.
The FDA granted an accelerated approval for Imbruvica as a single agent for the treatment of patients with MCL or CLL who have received at least one prior therapy. The accelerated approval for these indications was based on the overall response rate of patients in the phase II clinical studies of PCYC-1102 and PCYC-1104. An improvement in survival or disease-related symptoms was not established in these studies.
Imbruvica is an oral therapy that inhibits Bruton’s tyrosine kinase. BTK is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells. To date, nine phase III trials have been initiated with ibrutinib.
