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Monday, August 5, 2019

Alnylam: FDA Gives Priority Review for Givosiran New Drug Application

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) for givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) in development for the treatment of acute hepatic porphyria (AHP), and granted Priority Review for the NDA. A Priority Review designation is granted to medicines that the FDA has determined have the potential to provide significant improvements in the treatment, prevention or diagnosis of a serious disease, and FDA’s goal is to take action within six months compared to 10 months under standard review.
The FDA has set an action date of February 4, 2020 under the Prescription Drug User Fee Act (PDUFA), and the agency has indicated that they are not currently planning an advisory committee meeting as part of the NDA review.
Additionally, the Marketing Authorisation Application (MAA) for givosiran has been submitted to and validated by the European Medicines Agency (EMA). Givosiran was previously granted an accelerated assessment by the EMA, which is awarded to medicines deemed to be of major public health interest and therapeutic innovation, and is designed to bring new treatments to patients more quickly. Accelerated assessment potentially reduces the Agency’s evaluation time from 210 to 150 days.
Givosiran also previously received Breakthrough Therapy Designation from the FDA and Orphan Drug Designation in the U.S., as well as Priority Medicines (PRIME) Designation from the EMA and Orphan Drug Designation in the EU.

Cancer Survival Linked to Antidepressant Adherence

A large cohort study of Israeli patients with cancer found that antidepressant adherence above 50% was associated with one quarter less mortality over 4 years compared with adherence below 20%.
The study was published online July 22 in Depression and Anxiety.
However intriguing the results, this study is unlikely to change practice until the reason for the link is better understood, said psychiatrist Gary Rodin, MD, who heads up the Department of Supportive Care at the Princess Margaret Cancer Centre in Toronto, Canada.
“The implication of the paper is that the treatment of depression improves mortality, but I don’t think the paper necessarily proves that,” said Rodin. “Assuming this relationship is valid, the question is, what accounts for it? Correlations do not prove causation.”
For the study, Gal Shoval, MD, of Tel Aviv University, and colleagues analyzed data from 42,075 patients served by Clalit Health Services, the largest health provider in Israel. The researchers included all patients diagnosed with malignant neoplasm from the time each patient was first prescribed an antidepressant during his or her cancer. Adherence was defined as the ratio between the number of months the patient filled an antidepressent prescription and the number of months he or she was in the study.
The researchers reported that any adherence above 20% was linked to increased survival over the 4 years of the study. The apparent benefit maxed out at 50%-80% adherence, with a 23% reduction in the patient’s risk of death over 4 years. Adherence above 80% did not appear to confer any additional benefit.
The methodology of the study was reasonable, said Rodin. “It’s not a bad measure [of compliance]. If they filled the prescription, they’re more likely to take it than people who didn’t fill it. You still don’t know they took it but it’s a not an unreasonable measure, especially in a large study.”
Rodin said that, in general, the sample size — with over 1 million person-years of follow up — was the study’s major strength.
However, Rodin said that it is hard to apply the findings to clinical practice since the study shows an association but has failed to deliver on causality. He rejects any suggestion of a direct biological effect of antidepressants on cancer survival.
“The people who are compliant with [antidepressant] medications may be different to people who are noncompliant,” Rodin said. “They may have different lifestyle behaviors, they may be more compliant with cancer treatment.”
Rodin cites a classic breast cancer study published in The Lancet in 2000 that showed 92% of nondepressed women accepted adjuvant chemotherapy. By contrast, only half of depressed women in the study agreed to chemotherapy.
“The present study tracked compliance with antidepressant treatment, but they didn’t track compliance with anti-cancer treatment.” Rodin said. “It may be that people who were compliant with depression treatment [in this study] were more compliant with all treatment.”
In addition, there are no details of what the antidepressants were prescribed for, or if the patient needed antidepressants at all, said Rodin — or how they responded to treatment.
“I would like to know more about the severity of the depression, which they didn’t measure. That’s a limitation of the study,” he said. “If they showed that people who lived longer not only took the antidepressant medication but their depression remitted that would be a lot more convincing.”
In the article, Shoval and coauthors acknowledged that one of the study’s limitations was lack of data on the mental health diagnosis. They also conceded that unknown factors that stacked the odds against survival could have been more common in the noncompliant patients, noting, “there might be still residual confounding by unmeasured variables, such as grading and staging of the neoplasm.”
Rodin concluded: “So I think’s it’s premature to say that more adherence causes reduced mortality, but it’s an interesting finding and bears further investigation.”
Shoval and coauthors have disclosed no relevant financial relationships.
Depression and Anxiety. Published online July 22, 2019. Full text

Surge of Gun Violence Forces Chicago Hospital to Divert Patients

While the US was reeling over the weekend from two mass shootings in Texas and Ohio, Chicago was dealing with its own all-too familiar crisis related to gun violence.
Multiple gunshot victims sent to Mt. Sinai Hospital in Chicago early Sunday morning forced the hospital to temporarily divert ambulance traffic to other area trauma centers.
Chicago’s gun violence came amid mass shootings in El Paso, Texas and Dayton, Ohio, that left at least 31 people dead and dozens injured.
Overall in Chicago, at least seven people were killed and 48 wounded by guns in what was the city’s most violent weekend this year, according to the Chicago Tribune.
Dan Regan, director of communications and public relations for Sinai Health System, told Medscape Medical News on Monday that there was a shooting in Douglas Park near Mt. Sinai about 1:30 AM Sunday.
Seven people were shot there, he said, five of whom were sent to Mount Sinai.
“In addition to those five patients, we also received a couple of trauma patients from two motor vehicle accidents that occurred at the same time. That volume briefly led us to go on bypass, which simply means that ambulances bypass our hospital and go to a different trauma center,” Regan said.
He said Mt. Sinai — one of five level 1 trauma centers in Chicago — was on bypass from 4:30 AM to 6:30 AM.
“We were still accepting walk-in patients. We were just on bypass for ambulance traffic,” he said.
The rush of seven patients in addition to the other emergency department patients already getting treatment and walking in pushed the hospital to enact what is a “relatively unusual” step, Regan said. He said bypass is ordered at the hospital only a few times a year.
“There’s a coordinated effort with (emergency medical services) and the other trauma centers to direct other ambulances and ensure there is proper care for patients,” he said.
Regan said the health system doesn’t track the numbers of patients who would have come to Mt. Sinai had the bypass not been in effect.
Nancy Foster, the American Hospital Association’s vice president of quality and patient safety policy, told Medscape Medical News that in many communities nationwide, EDs are having surges in demand from the opioid crisis and virus outbreaks, along with the usual accidents and illnesses.
“When a hospital receives a large number of critical patients all at once who fully engage the available doctors, nurses, and other staff and resources, the emergency department may go on diversion as a way to ensure its staff can continue to focus on the patients who have already arrived, and other hospitals can be called on to attend to additional patients rapidly,” she said.
“Diversion is not a perfect solution to overcrowding in an emergency room, but it is one strategy many hospitals use,” Foster explained. “Some hospitals and emergency response teams are experimenting with other strategies for ensuring that patients’ needs are met in a timely fashion, and the AHA shares successful strategies with others around the country as they emerge.”

“Public Health Epidemic”

The Texas and Ohio shootings challenged several other emergency departments nationwide.
In El Paso, a mass shooting at a crowded department store on Saturday killed at least 22 people. The updated toll included a death late Sunday night and early Monday morning, according to the Associated Press. Police have a suspect in custody.
Hours after the El Paso shooting, on Sunday in Dayton, Ohio, a gunman opened fire on a crowd in a popular entertainment district, killing at least nine and injuring 27, according to the AP. The suspect was killed by police within a minute of the start of the rampage, the AP said.
The shooting in Dayton is the 22nd mass killing this year in the United States, according to the AP/USA Today/Northeastern University mass murder database. The 20 before this weekend have resulted in 96 deaths.
Vidor Friedman, MD, president of the American College of Emergency Physicians, said in a statement:
“News reports are numbing, and even the most well-intentioned thoughts and prayers fall short. As emergency physicians, we are on the frontlines of treating the victims of these senseless, violent acts. The frequency of firearm injuries and fatalities in this country is staggering, and there is no doubt about the threat posed to America’s public health and safety.”
Friedman added, “Firearm injuries — accidental or otherwise — should be addressed as a public health epidemic, with investments in research and a sweeping commitment to change that matches or exceeds the level of a number of diseases, outbreaks, or disorders that capture the public conscience but have exacted far less of a human toll in recent years.”

Earnings after Tuesday Aug. 6 close

Bausch Health Companies Q2 2019 Earnings Preview

Bausch Health Companies (NYSE:BHC) is scheduled to announce Q2 earnings results on Tuesday, August 6th, before market open.
The consensus EPS Estimate is $1.06 (+14.0% Y/Y) and the consensus Revenue Estimate is $2.15B (+0.9% Y/Y).
Over the last 2 years, bhc has beaten EPS estimates 75% of the time and has beaten revenue estimates 50% of the time.
Over the last 3 months, EPS estimates have seen 11 upward revisions and 3 downward. Revenue estimates have seen 8 upward revisions and 4 downward.

Earnings before Tuesday Aug. 6 open

Endo EPS beats by $0.04, beats on revenue

Endo (NASDAQ:ENDP): Q2 Non-GAAP EPS of $0.52 beats by $0.04; GAAP EPS of -$0.47 misses by $0.42.
Revenue of $699.73M (-2.1% Y/Y) beats by $5.13M.
Shares +1.75% AH.