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December 20, 2014 – Right in time for Christmas, the American Food & Drug Admininistration (FDA) on December 19 approved three significant new drugs, namely Ceftolozane/Tazobactam (Zerbaxa), Ombitasvir/Paritaprevir/Ritonavir co-packaged with Dasabuvir (Viekira Pak) and Olaparib (Lynparza), each of which represents a significant contribution to the therapy options of the targeted patient groups or subgroups.
First of all, FDA approved Zerbaxa (ceftolozane/tazobactam), a new antibacterial drug product, to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Zerbaxa is a combination product containing ceftolozane, a cephalosporin antibacterial drug, and tazobactam, a beta-lactamase inhibitor. Zerbaxa is used to treat cUTI, including kidney infection (pyelonephritis). It is used in combination with metronidazole to treat cIAI. Zerbaxa is the fourth new antibacterial drug approved by the FDA this year. The agency approved Dalvance (dalbavancin) in May, Sivextro (tedizolid) in June and Orbactiv (oritavancin) in August.
Zerbaxa is the fourth new antibacterial drug product designated as a Qualified Infectious Disease Product (QIDP) to receive FDA approval. Under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act, Zerbaxa was granted QIDP designation because it is an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection. As part of its QIDP designation, Zerbaxa was given priority review, which provides an expedited review of the drug’s application. The QIDP designation also qualifies Zerbaxa for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug and Cosmetic Act.
Zerbaxa’s efficacy to treat cIAI in combination with metronidazole was established in a clinical trial with a total of 979 adults. Participants were randomly assigned to receive Zerbaxa plus metronidazole or meropenem, an FDA-approved antibacterial drug. Results showed Zerbaxa plus metronidazole was effective for the treatment of cIAI. The efficacy of Zerbaxa to treat cUTI was established in a clinical trial where 1,068 adults were randomly assigned to receive Zerbaxa or levofloxacin, an antibacterial drug approved by the FDA to treat cUTI. Zerbaxa demonstrated it was effective in treating cUTI. The Zerbaxa label includes a warning about decreased efficacy seen in patients with renal impairment. The most common side effects identified in the clinical trials were nausea, diarrhea, headache and fever (pyrexia).
The second drug just approved is Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets) to treat patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with a type of advanced liver disease called cirrhosis. Hepatitis C is a viral disease that causes inflammation of the liver that can lead to reduced liver function, liver failure or liver cancer. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades. According to the Centers for Disease Control and Prevention, about 3.2 million Americans are infected with HCV, and without proper treatment, 15-30 percent of these people will go on to develop cirrhosis. Viekira Pak contains three new drugs—ombitasvir, paritaprevir and dasabuvir—that work together to inhibit the growth of HCV. It also contains ritonavir, a previously approved drug, which is used to increase blood levels of paritaprevir. Viekira Pak can be used with or without ribavirin, but it is not recommended for patients whose liver is unable to function properly (decompensated cirrhosis). Viekira Pak is the fourth drug product approved by the FDA in the past year to treat chronic HCV infection. The FDA approved Olysio (simeprevir) in November 2013, Sovaldi (sofosbuvir) in December 2013 and Harvoni (ledipasvir and sofosbuvir) in October 2014. Viekira Pak’s efficacy was evaluated in six clinical trials enrolling 2,308 participants with chronic HCV infection with and without cirrhosis.
In different trials, participants were randomly assigned to receive Viekira Pak or placebo (sugar pill); Viekira Pak with or without ribavirin; or Viekira Pak with ribavirin for 12 or 24 weeks. The trials were designed to measure whether the hepatitis C virus was no longer detected in the blood at least 12 weeks after finishing treatment (sustained virologic response, or SVR), indicating that a participant’s HCV infection has been cured. Results from multiple populations, including those considered difficult to treat, showed 91 to 100 percent of participants who received Viekira Pak at the recommended dosing achieved SVR. The recommended dosing for Viekira Pak is two ombitasvir, paritaprevir, ritonavir 12.5 milligrams (mg)/75 mg/50 mg tablets once daily and one dasabuvir 250 mg tablet twice daily. The most common side effects reported in clinical trial participants were feeling tired, itching, feeling weak or lack of energy, nausea and trouble sleeping.
Last but not least FDA also approved Olaparib (Lynparza) as monotherapy for the treatment of patients with deleterious or suspected deleterious germline BRCA mutated (gBRCAm) (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Concurrent with this action, FDA approved the BRACAnalysis CDx (Myriad Genetics) for the qualitative detection and classification of variants in the BRCA1 and BRCA2 genes.
The approval is based on objective response rate (ORR) from the international, single-arm trial in patients with deleterious or suspected deleterious gBRCAm advanced cancers. The trial enrolled 137 patients with measurable, gBRCAm-associated ovarian cancer treated with three or more prior lines of chemotherapy. Treatment continued until disease progression, unacceptable toxicity, and/or consent withdrawal. Of the 137 patients, 93% had ECOG performance status of 0 or 1. Deleterious or suspected deleterious gBRCAm status was verified retrospectively in 97% (59/61) of the patients for whom blood samples were available by the companion diagnostic BRACAnalysis CDx. The trial results demonstrated an ORR of 34% (95% CI: 26, 42). The median response duration was 7.9 months (95% CI: 5.6, 9.6).
The most common adverse reactions (greater than or equal to 20%) in patients treated with olaparib were anemia, nausea, fatigue (including asthenia), vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash and abdominal pain/discomfort. Myelodysplatic syndrome and/or acute myeloid leukemia occurred in 2% of the patients enrolled on this trial. The recommended olaparib dose is 400 mg orally twice daily.