Erin Johanek, PharmD, RPh

 recently announced the primary results from a study comparing Tresiba (insulin degludec injection 100 units/mL, Novo Nordisk) to insulin glargine 100 units/mL.

	The DEVOTE study was the first randomized, double-blind, treat-to-target, event-driven trial comparing the 2 basal insulins in adults with type 2 diabetes at high risk of cardiovascular (CV) disease. The results of the trial were presented at the American Diabetes Association’s 77

	Tresiba is a once-daily basal insulin used to control high blood sugar in adults and children who are aged 1 year and older with diabetes.

	The DEVOTE study involved 7,637 people with type 2 diabetes followed for approximately 2 years. Patients were randomized to receive either Tresiba (3818 patients) or insulin glargine U100 in vial (3,819 patients) in addition to standard of care.

	Results of the trial demonstrated that Tresiba met the primary end point of non-inferiority compared with insulin glargine U100 for major adverse CV events (MACE). Additionally, the findings for each component of MACE were consistent with the overall endpoint, including the first occurrence of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke.

	“The main purpose of the DEVOTE study was to rule out excess cardiovascular risks,” explained Todd Hobbs, MD, chief medical officer, Novo Nordisk US. “If there were any debating or residual questions about cardiovascular risks with Tresiba, these are gone now.”

	Results also showed a 40% reduction in the rate of severe hypoglycemia and a 53% reduction in the rate of nocturnal severe hypoglycemia with Tresiba compared to insulin glargine U100. Researchers defined severe hypoglycemia as an episode requiring assistance of another person and nocturnal severe hypoglycemia occurred between the hours of 00:01 and 05:59.

	“Previous data hints or suggests that there is a reduction in hypoglycemia with Tresiba but until this point, it has been challenging to prove,” Hobbs said. “With a 40% reduction in overall severe hypoglycemia and 53% reduction in severe hypoglycemia at night time, these episodes can be more clearly related to costs in the healthcare system regarding falls and ER visits and this is important information for anyone making a formulary decision that could impact many lives.”

	Post hoc analyses showed similar levels of glycemic control with an end of trial hemoglobin A1c estimated treatment difference of 0.01% between the 2 treatment groups and significantly lower fasting plasma glucose levels with Tresiba after 2 years compared to insulin glargine U100 with an estimated treatment difference of -7.2 mg/dL.

	In the DEVOTE study, adverse events leading to permanent discontinuation of the investigational product occurred in 5.2% of patients receiving Tresiba and 5.8% of patients receiving insulin glargine U100. 

	Common side effects associated with the use of Tresiba include injection site reactions, itching, rash, serious allergic reactions, weight gain, and swelling of hands or feet.

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Novo Nordisk’s DEVOTE study reveals interesting findings.

Popular insulin meets target in real-world study

	FDA has approved Thermo Fisher Scientific's Oncomine Dx Target Test, the first next-generation sequencing (NGS)-based companion diagnostic that can simultaneously screen for multiple therapies to treat non-small cell lung cancer (NSCLC).

, lung cancer is the leading cause of cancer death among both men and women in the United States, accounting for about 1 in 4 cancer deaths. Additionally, NSCLC makes up about 80% to 85% of all cases of lung cancer.

	The Oncomine Dx Target Test simultaneously evaluates 23 genes clinically associated with NSCLC and results from the analysis of three of these genes can now be used to identify patients who may be eligible for treatment with FDA-approved therapies, including the combination of Novartis’ Tafinlar and Mekinist (dabrafenib and trametinib), Xalkori (crizitonib, 

	The Oncomine Dx Target Test provides a new testing method that saves time for the patient to get on the right therapy the first time and helps reduce overall healthcare costs associated with the guesswork that goes into the sequential testing approach when using single-biomarker tests,” said Joydeep Goswami, president of Clinical Next Generation Sequencing and Oncology for Thermo Fisher Scientific.

	“The Oncomine Dx Target Test provides a new testing method that saves time for the patient to get on the right therapy the first time and helps reduce overall healthcare costs associated with the guesswork that goes into the sequential testing approach when using single-biomarker tests,” said Joydeep Goswami, president of clinical sequencing for Thermo Fisher Scientific.

 are among the first laboratories that will offer the new test as a service to oncologists.

	The Oncomine Dx Target Test was developed in collaboration with 

 Ion AmpliSeq technology, which enables screening of tumor samples using a very small quantity of preserved biopsy sample. Goswami explains that this is a critical advantage since samples from NSCLC patients are usually very limited in quantity.

	“FDA approval of the Oncomine Dx Target Test is the first step in making precision oncology technology a reality; now, NSCLC patients and their oncologists have access to a molecular test that returns result in a few days,” said Goswami. “Rapid identification of a targeted therapy is crucial for these patients, who don’t have time to spare due to the late-stage of their cancer.”

 plans to extend the test to include additional genes and submit to FDA so it can serve as a companion diagnostic for other indications beyond NSCLC.

	The Oncomine Dx Target Test is expected to be available in the United States in August 2017.

FDA approves new diagnostic test for non-small cell lung cancer.

New universal companion diagnostic paves the way for precision oncology

) has been FDA-approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible bacteria.

	Baxdela is the newest member of the fluoroquinolone antibiotic class and exhibits activity against both gram-positive and gram-negative bacteria.

	Approximately 3 million patients are hospitalized each year in the United States with ABSSSI. These patients often present treatment challenges owing to their underlying medical conditions, making optimal antibiotic selection difficult, explained Sue Cammarata, MD, Melinta chief medical officer.

	Baxdela is available in both intravenous (IV) and oral formulations. The 450-mg tablet is bioequivalent to and interchangeable with the 300-/mg IV dose, and can be dosed without regard to food. The only drug-drug interaction expected with Baxdela is the co-administration with chelating agents, such as antacids.

	As for the differences between Baxdela and previously approved fluoroquinolones, Camarrata explains that Baxdela is the only fluoroquinolone that can be used in MRSA infection; and unlike the others, it is not associated with QT prolongation or photosensitivity.

	“Unlike many recent antibiotics approved for serious skin infections, Baxdela can also treat gram-negative bacteria, which can be seen in patients with complicated medical histories, such as those with diabetes, renal disease, vascular disease and obesity” Cammarata said. “Baxdela has both IV and oral formulations, which increases the options for physicians who are treating these complicated patients.”

	The approval of Baxdela is based on two phase 3 clinical trials in patients with ABSSSI. Results of the trials determined that IV and oral Baxdela monotherapy was statistically non-inferior to the combination of vancomycin and aztreonam in the primary end point of early clinical response at 48 to 72 hours, as well as the secondary end point of clinical success at Day 14.

	Baxdela was given priority review by FDA due to its designation as a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act of 2012. This qualifies Baxdela for incentives related to the development of new antibiotics, including a five-year extension of any non-patent exclusivity period awarded to the drug.

	In trials, Baxdela was well tolerated with a 0.9% discontinuation rate due to adverse reactions. The most common adverse reactions associated with the use of Baxdela in clinical trials were nausea, diarrhea, headache, transaminase elevations, and vomiting.

	Serious adverse reactions associated with the use of all fluoroquinolones include tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects. If these occur, patients are to immediately discontinue Baxdela and avoid use of any fluoroquinolone. It should be noted that there were no events of tendon rupture in Baxdela clinical trials.

FDA approved the use of a new fluoroquinolone antibiotic to treat ABSSSI.

New antibiotic approved for acute bacterial skin infections

	FDA has requested that Endo Pharmaceuticals remove its opioid pain medication, Opana ER (oxymorphone hydrochloride) from the market due to the agency’s concerns that the benefits of the medication do not outweigh its risks related to abuse.

	This is the first time that the FDA has asked a manufacturer to remove its opioid pain medication from the market due to the public health consequence of abuse and the agency says it will continue to examine the risk-benefit profile off all approved opioid analgesics and take actions appropriately as part of the response to the opioid epidemic.

	“FDA putting its foot down to have this drug removed as a legal prescription is what is needed with the current opioid epidemic,” said Stephanie Higashi, DC, chief executive of the integrated healthcare practice 

. “Allowing for highly addictive medications to be provided to patients who may not be told the extreme risks may result in a lifetime of pain, addiction, loss and even death.”

	According to Higashi, “Given that Opana has a high risk of abuse and is dangerously addictive, it is even more critical to have it removed from the market. The drug also has a very long half-life, meaning the amount of time it stays in the body and it takes the body to metabolize the drug out of the body.”

	Oxycodone, for example has a half-life of approximately 3.5 hours whereas Opana has half-life 7 to 9 hours, according to Higashi. “Thus, the drug is kept in the body longer and even more dangerous if a person is to have a reverse reaction it is in their body longer than something that would wear off after a few hours.”

	According to the CDC, deaths from prescription opioids, like oxycodone, hydrocodone, and methadone, have more than quadrupled since 1999 and it is estimated that 91 Americans die every day from an opioid overdose, including prescription opioids and heroin.

	Opana ER is an opioid agonist indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Opana ER was first approved in 2006 but in 2012, 

 replaced the original formulation with a new formulation that was intended to make the drug resistant to physical and chemical manipulation for abuse by snorting or injecting.

	The new formulation did meet the regulatory standards for approval. However, FDA determined that the data did not show that the reformulation could be expected to meaningfully reduce abuse and therefore declined the manufacturer’s request to include labeling describing potentially abuse-deterrent properties for the new formulation of Opana ER.

	FDA’s decision to ask for removal of the opioid pain drug is based on a review of all available postmarketing data, which demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation. Abuse by injection of the reformulated drug has been associated with an outbreak of HIV and hepatitis C, as well cases of thrombotic microangiopathy, a potentially life-threatening condition caused by small-vessel platelet microthrombi.

	“The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market,” said Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research. “This action will protect the public from further potential for misuse and abuse of this product.”

	Meanwhile, FDA wants healthcare professionals and others to be aware of the potentially serious risks associated with the abuse of Opana ER.

Potential public health consquences prompts FDA to request removal of opioid pain medication.

FDA to drug maker: Pull opioid pain drug

	FDA approved epinephrine injection (Symjepi, 

	Mylan made headlines last summer for reportedly repeatedly raising the price of its life-saving medication. It increased the price of a pair of EpiPens from $94 in 2007 to $608 last year. After receiving backlash due to the price hike, Mylan launched generic EpiPens last December.

	Symjepi is indicated in the emergency treatment of allergic reactions to stinging and biting insects, allergen immunotherapy, foods, drugs, diagnostic testing substances, and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis.

	Currently, brand EpiPens cost about $630 to $700 without insurance while the new generic version retails for about $225 to $425. It is estimated that is costs less than $20 to produce a pair of EpiPens.

	According to Adamis, Symjepi is intended to be a low-cost alternative to EpiPen and similar products, and the company is aiming to sell it for less than generic EpiPens. The manufacturer said that Symjepi is easier to use than EpiPen and is also smaller than EpiPen so it is easier to fit in a pocket or purse.

	"For better or worse, whether you look at things half full or half empty we have a capitalistic society," said Stephanie Higashi, DC, chief executive of the integrated healthcare practice 

. "An open marketplace with competition and a society that thrives, drives on 'opportunity'-the American Dream getting and being rich. There are balance sheets, shareholders, profit margins, overhead and many people working to find a way to make more money and profit. What does this have to do with an Epipen? Well, Symjepi will likely be a lower cost option that’s more attainable. I am certain even a billionaire with a heart wouldn't want to see a person gasping for their last breath of air because they couldn't afford a $608 epi-pen when the cost to produce it to save the person's life is a mere $20."

	Symjepi will be available as a single-dose, pre-filled syringe for manual injection containing 0.3 mg/0.3 mL epinephrine sterile solution for injection. Patients greater than or equal to 30 kilograms (66 pounds) are to inject Symjepi intramuscularly or subcutanteously into the anterolateral aspect of the thigh, through clothing if necessary.

	Like EpiPen, Symjepi is expected to be sold in pairs, which makes it more convenient for children and adults with severe food or insect allergies that carry a device on the go and leave a spare at home, school or work. Additionally, Adamis is preparing to apply for FDA approval of a “junior version” of Symjepi, that would contain a lower epinephrine dose and would compete with Mylan’s EpiPen Jr.

	Adverse reactions to all epinephrine products include anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitation, nausea and vomiting, headache, and/or respiratory difficulties.

	Adamis is still lining up a distributor so the price of the medication is not currently known but Symjepi is expected to go on sale later this year.

Adamis’ epinephrine injection promises to be a lower-cost alterative to EpiPen.

FDA approves EpiPen rival

	FDA has approved the first generic version of 

 Truvada (emtricitabine and tenofovir disoproxil fumarate) for the treatment of HIV-1, in combination with other antiretroviral agents, as well as for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to prevent sexually acquired HIV infection in adults at high risk.

 will manufacture the generic version and has 

 reached a confidential settlement on exactly when it will roll out into the market.

	Truvada is the brand name combination of emtricitabine, a synthetic cytosine analog, and tenofovir disoproxil fumarate (DF), an adenosine 5’-monophosphate analog. Each drug interferes with HIV viral RNA-dependent DNA polymerase thereby inhibiting viral replication. Emtricitabine and tenofovir DF should not be used concurrently with adefovir or lamivudine-containing products or other emtricitabine- and/or tenofovir-containing products.

	The generic combination is approved for treatment of HIV-1, in combination with other antiretroviral medications, and for PrEP in adults at high risk of sexually acquired HIV infection. PrEP may be a part of a comprehensive HIV prevention plan that includes safer sex practices, such as consistent and correct condom use, regular HIV testing and risk reduction counseling. In PrEP, HIV-uninfected individuals who are at high risk of sexually-acquired HIV infection take antiretroviral medication daily to try to decrease the chance of becoming infected with HIV if exposed to the virus.

	Emtricitabine and tenofovir DF used for PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initial use and periodically thereafter. Drug-resistant HIV-1 variants have been identified with the use of emtricitabine and tenofovir DF for PrEP following undetected HIV-1 infection therefore, the medications should not be initiated in any patient for PrEP if signs or symptoms of acute HIV infection are present unless HIV-negative status is confirmed.

	In clinical trials, the most common side effects associated with the use of emtricitabine and tenofovir DF in the treatment of HIV-infected individuals included diarrhea, nausea, fatigue, headache, dizziness, abnormal dreams and rash. the most common adverse reactions in PrEP patients included headache, abdominal pain, and weight loss.

	Emtricitabine and tenofovir DF must be dispensed with a Medication Guide, which explains the drug’s intended uses and risks. Patients with kidney dysfunction may require less-frequent dosing and women who are HIV-positive should not breastfeed while taking emtricitabine and tenofovir DF.

The first generic Truvada for treating and preventing HIV will be available, but when?