Christine Blank, Contributing Editor

FDA is re-examining the safety of a breakthrough Parkinson’s disease drug after reports of hundreds of deaths.

Pimavanserin (Nuplazid, Acadia Pharmaceuticals), the only drug approved to treat hallucinations and delusions associated with Parkinson's disease psychosis, is suspected in hundreds of deaths voluntarily reported by caregivers, doctors and other medical professionals since it hit the market, 

"What does it take for a drug like this to be taken off the market?" asked US Rep. Rosa DeLauro, former chair of the congressional subcommittee responsible for funding and overseeing FDA, at a recent Congressional hearing, 

 reported. "How many more adverse events do we have to have reported? How many people, quite frankly, have to die?” DeLauro asked FDA Commissioner Scott Gottlieb, MD, at the hearing.

However, FDA had already begun conducting a new review of the drug because of "potential signals of serious risk/new safety information" in part by using adverse event data, 

 reported. However, the agency is not suggesting physicians stop prescribing the drug while a safety evaluation is taking place.

Death reports citing Nuplazid have typically involved elderly patients with advanced-stage Parkinson's disease who suffered from numerous medical conditions, according to FDA.

However, the high number of death reports deserved a closer look to determine whether they were related to the drug, sooner, medical experts and physicians told 

. “They also recommended further testing of Nuplazid, worrying that the drug had been approved too quickly, based on too little evidence that it was safe or effective,” 

Nuplazid's review was expedited by FDA because it had been designated a breakthrough therapy.

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FDA reviewing safety of Parkinson’s drug

After FDA approved the first epinephrine injection specifically for infants and toddlers last year, the drug is now on the market.

The epinephrine injection (AUVI-q, Kaleo) 0.1 mg for infants and toddlers has a shorter needle length and lower dose of epinephrine than other FDA-approved epinephrine auto-injectors (EAIs), kalÃ©o said in a statement.

The product is needed, according to the pharma manufacturer, because there was an estimated 130% increase in emergency room visits for anaphylaxis among children four years old and younger between 2005 and 2014.

“Before the introduction of AUVI-q 0.1 mg, the youngest and most vulnerable population did not have a treatment for anaphylaxis designed for them,” said Eric S. Edwards, MD, PhD, vice president of innovation and research & development at kalÃ©o. “This day means a lot to me personally, as I suffer from life-threatening allergies and have a child who was diagnosed with life-threatening allergies as an infant.”

“I would have loved to have had the AUVI-q 0.1 mg available back when my son was an infant and was first diagnosed with an egg and wheat allergy,” said Todd Mahr, MD, a pediatric allergist and president-elect of the American College of Allergy, Asthma and Immunology, in the statement. “Prior to this, there was no EAI specifically designed for infants and toddlers weighing 16.5 to 33 pounds, so the AUVI-q 0.1 mg helps to address that significant unmet need.”

Each AUVI-q 0.1 mg prescription includes 2 auto-injectors and 1 Trainer for patients and caregivers to practice administration before an allergic emergency. AUVI-q 0.1 mg features a voice instruction system that helps guide caregivers step-by-step through the injection process, as well as a needle that automatically retracts following administration.

 First infant epinephrine injector on market

	Walmart, CVS Health, and a number of other healthcare organizations are supporting a new multi-million dollar consumer campaign to combat high prescription drug prices.

	The Campaign for Sustainable Rx Pricing (CSRxP), a coalition of leaders that also includes AARP, the American Hospital Association and the American Academy of Family Physicians, launched the nationwide campaign in early May “to hold Big Pharma accountable for their out-of-control prescription drug prices,” the group said in a statement.

	CSRxP debuted the first in a series of nationwide advertisements, “

,” on broadcast and cable television that will run in Washington, D.C., and in the districts of key lawmakers around the country.

	The ads highlight the “hypocrisy of Big Pharma’s claims that out-of-control prescription drug prices are necessary to fund research and development,” CSRxP said. “The truth is, nine out of 10 of the biggest drug manufacturers in the United States spend more on advertising than they do on R&D,” the group said.

	“American Society of Health-System Pharmacists members have identified this as a huge problem and a growing burden on hospital pharmacy budgets,” Joseph Hill, director of ASHP’s Government Relations Division, told 

 “The new advertising campaign is a way to reach consumers directly and let them know this is a significant problem and that they’re not alone.”

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	However, the Pharmaceutical Research and Manufacturers of America (PhRMA) denounced the new price gouging campaign. “Rather than offering solutions, this advertisement makes light of the real challenges patients are facing when trying to access the health care they need,” Holly Campbell, senior director of public affairs for PhRMA, told 

We believe the focus should be on advancing common sense, practical solutions that 

	“On average, biopharmaceutical companies invest 20% of their revenue in R&D-far more than any other industry in the U.S. economy,” Campbell said.

 of a medicine with more than a third being rebated back to insurance companies, PBMs and the government, Campbell said.

Walmart, CVS Health, and a number of other healthcare organizations are supporting a new multi-million dollar consumer campaign to combat high prescription drug prices.

Campaign gears up to combat high drug prices

	Late last week, FDA approved a new drug to treat acute myeloid leukemia (AML), the first treatment for Batten disease, and expanded the use of a current drug to treat liver cancer.

) was approved to treat adults with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3, in combination with chemotherapy. The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay (

), used to detect the FLT3 mutation in patients with AML.
	 
	“Rydapt is the first targeted therapy to treat patients with AML, in combination with chemotherapy,” said Richard Pazdur, MD, 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. “The ability to detect the gene mutation with a diagnostic test means doctors can identify specific patients who may benefit from this treatment.”

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	AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream. The National Cancer Institute estimated that approximately 19,930 people would be diagnosed with AML in 2016 and 10,430 were projected to die of the disease.

	FDA also expanded the approved use of regorafenib (Stivarga, 

) to include treatment of patients with hepatocellular carcinoma (HCC or liver cancer) who have been previously treated with the drug sorafenib.

	“This is the first FDA-approved treatment for a liver cancer in almost a decade,” FDA said in a statement.

	Plus, limited treatment options are available for patients with liver cancer, said Richard Pazdur, MD, 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, in the statement.

	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.

	Meanwhile, FDA also approved the first treatment for a specific form of Batten disease: cerliponase alfa( Brineura (

), to slow loss of walking ability in symptomatic pediatric patients aged 3 years 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, MD, 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 (NCLs), 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.

	Batten disease is relatively rare, occurring in an estimated 2 to 4 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 aged 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.

Late last week, FDA approved a new drug to treat acute myeloid leukemia (AML), the first treatment for Batten disease, and expanded the use of a current drug to treat liver cancer.

FDA approves first targeted leukemia drug for certain patients, plus 2 more

	A new abuse-deterrent painkiller-oxycodone hydrochloride (RoxyBond, 

)–will be available soon after receiving FDA approval.

	RoxyBond, approved in 5 mg, 15 mg and 30 mg strengths, is an abuse-deterrent formulation of oxycodone that uses physical and chemical barriers to deter abuse, without the use of aversive agents or opioid antagonists. According to Inspirion, RoxyBond is the first immediate-release opioid analgesic approved with labeling describing its abuse-deterrent properties.

Abuse-deterrent opioid pain drug approved

’s oxycodone/naltrexone (Troxyca ER) extended-release, abuse-deterrent oxycodone. Troxyca ER has properties that are expected to reduce abuse when crushed and administered by the oral and intranasal routes, according to Pfizer.

	“Oxycodone immediate release opioid tablets are widely abused and the development of RoxyBond will offer clinicians a new approach for treating patients in pain while also fighting against the potential for abuse,” said Jeffrey Gudin, MD, department director of the Pain Management Center Englewood Hospital and Medical Center, in a statement from Inspirion.

	Using Inspirion's SentryBond technology, Roxybond is formulated with inactive ingredients that make the tablet more difficult to manipulate for misuse and abuse even if the tablet is subjected to physical manipulation and/or attempts at chemical extraction. “Laboratory test data demonstrated that, relative to another approved oxycodone immediate-release tablet, RoxyBond has increased resistance to cutting, crushing, grinding, or breaking using selected tools,” according to a statement from the company.

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	In addition, both intact and manipulated RoxyBond tablets resisted extraction in selected household and laboratory solvents under various conditions, including selected pre-treatments. Relative to oxycodone immediate-release tablets, the RoxyBond formulation forms a viscous material that resists passage through a needle; it was also more difficult to prepare solutions suitable for intravenous injection.

	“The in vitro data demonstrate that RoxyBond has physicochemical properties expected to make abuse via injection difficult.  However, abuse by the intranasal, oral, and intravenous route is still possible,” Inspirion said. A clinical abuse potential study was also conducted.

	"As reflected in the prescribing information, the data from the clinical study, along with support from in vitro data, indicate that RoxyBond has physicochemical properties that are expected to reduce abuse by the intranasal route of administration," said Lynn R. Webster, MD, principal investigator of PRA Health Sciences in Salt Lake City, Utah.

A new abuse-deterrent painkiller - oxycodone hydrochloride (RoxyBond, Inspirion Delivery Services) - will be available soon after receiving FDA approval.

New abuse-deterrent opioid available

	In what is expected to produce hefty savings for rheumatoid arthritis (RA) patients and the healthcare system, FDA approved the second biosimilar to Remicade (

 infliximab-abda (Renflexis) was just approved, after FDA approved the biosimilar infliximab-dyyb (Inflectra, 

) last year. The new drug will be marketed and distributed in the United States by Merck.

Another win for biosimilar arthritis drugs

	Renflexis, the first drug for Samsung Bioepsis in the United States, is indicated for reducing signs and symptoms in patients with RA, adult and pediatric Crohn’s disease, adult ulcerative colitis, ankylosing spondylitis and psoriatic arthritis, and for the treatment of adult plaque psoriasis.

	“Since our company was established five years ago, we have strived day in and day out to realize the promise of biosimilars for patients across the US by offering them treatment options at a lower cost. We hope this regulatory milestone will bring us a step closer to achieving this goal,” said Christopher Hansung Ko, president and CEO of Samsung Bioepis, in a statement from the company.

Biosimilar approvals deemed “too slow”

	The new biosimilar is also expected to impact Johnson & Johnson’s U.S. Remicade sales, which reached $4.84 billion in 2016.

	Renflexis has also been approved in 28 European Union (EU) member states, Norway, Liechtenstein, Iceland, Australia and Korea. 

In what is expected to produce hefty saving for rheumatoid arthritis patients and the healthcare system, FDA approved the second biosimilar to Remicade (Johnson & Johnson).