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Sunday, April 7, 2019

Allergan’s failed depression drug shows promise in opioid withdrawal

Last month, Allergan said that rapastinel—the centerpiece of its $560 million acquisition of Naurex—had failed in three pivotal trials in major depressive disorder. But not all is lost. Scientists at Duke University and Villanova University may have found a use for the drug in treating opioid withdrawal.
People who become dependent on opioids can experience excruciating withdrawal symptoms, such as anxiety, vomiting, diarrhea and insomnia. These symptoms often prevent them from seeking help, or they cause relapse in patients who do seek out treatment for addiction.
Rapastinel might help manage those symptoms, according to a new study by Julia Ferrante at Villanova University and Cynthia Kuhn at Duke University. The experimental drug substantially reversed acute withdraw signs in rats in three days, the researchers said in a release. The study was presented at the American Society for Pharmacology and Experimental Therapeutics annual meeting in Orlando.
There are FDA-approved drugs to treat opioid use disorder. Buprenorphine and methadone are commonly used to help eliminate the opioid cravings. But they are also opioids that can be abused, they can cause side effects, and patients sometimes need to use them over the long term to avoid relapse.
Two other drugs, naloxone and naltrexone, are not opioids. But patients need to detox before they can use naltrexone, and naloxone is more appropriate for use in emergency settings to reverse opioid overdoses.
Rapastinel, in comparison, binds to the same NMDA receptor that the “party drug” ketamine uses, but at a different site. In their study, Ferrante and Kuhn gave rat models of opioid dependence either rapastinel, ketamine or a saline solution. On the third day, rats given rapastinel showed significantly fewer signs of withdrawal than the other animals did, the researchers reported.

Opioid overdose has become a public health crisis in the U.S., with an estimated 130 people dying each day from opioid-related drug overdoses, according to the U.S. Department of Health and Human Services. While health regulators are pursuing tactics for cutting down on opioid use, scientists are stepping up their research efforts, looking for new ways to fight addiction.
Last May, the FDA greenlighted US WorldMeds’ Lucemyra as the first approved drug specifically for opioid withdrawal, even though the drug had been used for more than two decades in the U.S.
Scientists at the Walter Reed Army Institute of Research previously found a heroin vaccine could block the euphoric effects of opioids in the brain by blocking heroin from crossing the blood-brain barrier.
Although rapastinel’s use in depression turned out to be a dead end, clinical trials have shown it is well-tolerated in people. Before rapastinel can be moved into clinical trials in opioid withdrawal, more studies are needed to investigate its molecular effects and to determine whether it can reduce the possibility of relapse, according to the researchers.

Biotech week ahead, April 8

Biotech stocks ended higher for the second straight week, with the presentations at the American Association of Cancer Research annual meeting taking the spotlight. Additionally, there were clinical trial readouts from companies that carried a fourth-quarter timeframe.
ADMA Biologics Inc ADMA 2.12% shares rallied sharply after the  FDA nod for its immunodeficiency therapy. But Evoke Pharma Inc EVOK 0.98%‘s NDA for diabetic gastroparesis drug Gimoti received a thumbs-down from the regulatory agency, sending its shares down about 50% Tuesday.
Looking ahead to the unfolding week, the following are some key catalytic events biotech investors will be focusing on.

Conferences

  • Society for Inherited Metabolic Disorders 2019 annual meeting: April 6-9 in Bellevue, Washington.
  • H.C. Wainwright Global Life Sciences Conference: April 8-9 in London.
  • 13th International Conference on Endocrinology, Diabetes and Metabolism: April 8-9 in Wellington, New Zealand.
  • 12th World Conference on Human Genomics and Genomic Medicine: April 8-9, in Abu Dhabi, UAE.
  • 18th Annual Needham Healthcare Conference: April 9-10 in New York City.
  • 3rd International Conference on Influenza and Emerging Infectious Diseases: April 10-11 in Toronto, Canada.
  • 2019 Congress of the Schizophrenia International Research Society: April 10-14 in Orlando, Florida.
  • The European Association for the Study of the Liver, or EASL, International Liver Congress 2019:  April 10-14 in Vienna, Austria.
  • 12th World Congress on Dementia and Alzheimer Rehabilitation: April 11-12 in Stockholm, Sweden.
  • 29th European Congress of Clinical Microbiology & Infectious Diseases: April 13-16 in Amsterdam, Netherlands.

PDUFA Dates

The FDA is set to rule on Merck & Co., Inc. MRK 0.83%‘s sBLA for Keytruda as a monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer in patients whose tumors express PD-L1 without EGFR or ALK genomic tumor aberrations. The FDA decision is due Thursday, April 11.

Clinical Trial Readouts

Alkermes Plc ALKS 3.51% is due to release new Phase 3 data for ALKS 3831, which is being evaluated in a study dubbed ENLIGHTEN-2 for schizophrenia, at the 2019 Congress of the Schizophrenia International Research Society on Thursday, April 11.

The EASL International Liver Congress 2019 Presentations

Thursday, April 11
  • Eiger Biopharmaceuticals Inc EIGR 1.03%: Late-breaker presentation of already released Phase 2 data for pegylated interferon lambda (hepatitis delta virus).
  • Assembly Biosciences Inc ASMB 4.74%: Poster presentation of Phase 1a data for ABI-H2158 (hepatitis B virus).
  • Intercept Pharmaceuticals Inc ICPT 1.12%): Full Phase 3 data for Ocaliva from the REGENERATE study (non-alcoholic steatohepatitis).
  • Viking Therapeutics Inc VKTX 2.91% and Ligand Pharmaceuticals Inc. LGND 1.15%: additional Phase 2 data for VK2809 (hypercholesterolemia and non-alcoholic fatty liver disease, or NAFLD).
Friday, April 12
  • Spring Bank Pharmaceuticals Inc SBPH 0.42%: full Phase 2 data for inarigivir and vemlidy (hepatitis B virus).
  • Albireo Pharma Inc ALBO 0.23%: Phase 2 data for A4250 (liver disease).
  • Altimmune Inc ALT 2.84%: Phase 1 data for HepTCell (hepatitis B).
Saturday, April 13
  • Assembly Biosciences: Interim Phase 2a data for AB-H0731 (hepatitis B virus).
  • Conatus Pharmaceuticals Inc CNAT 3.85%: Late-breaker presentation of Phase 2b data for emricasan (NASH cirrhosis).

29th European Congress of Clinical Microbiology & Infectious Diseases Presentations

Saturday, April 13
  • SCYNEXIS Inc SCYX: Phase 3 data for oral SCY-078 (candida auris).
  • Cidara Therapeutics Inc CDTX: new analysis from Phase 2 STRIVE B for Rezafungin (candidemia).

J&J wins trial over Cal. man’s talc-cancer claim

Johnson & Johnson won the latest trial over claims its iconic baby powder can cause cancer, as a jury in Long Beach, California, rejected a lawsuit brought by a 65-year-old retired teacher who claimed the product was contaminated with asbestos.
The J&J victory Friday comes the week after the company settled three cases alleging baby powder caused a rare asbestos-connected cancer. Two, in Oklahoma and California, were settled during trial. The other, in New York, was settled less than two weeks before trial was set to begin.
Plaintiff Robert Blinkinsop was diagnosed in July 2017 with mesothelioma, a rare cancer of the lining of the lung generally caused by asbestos exposure. Blinkinsop used Johnson’s baby powder daily for personal hygiene from 1977 to 1994 and on his children from 1992 to 1996, his attorney, Mark Bratt, said at trial. He also used the company’s Shower to Shower talc product.
J&J is facing more than 13,000 lawsuits linking baby powder and another talc product, Shower to Shower, to ovarian cancer or mesothelioma. More than two dozen trials have been scheduled in U.S. courts in 2019.
“Today’s jury unanimously ruled that Johnson’s Baby Powder does not contain asbestos and was not the cause of the plaintiff’s disease,’’ Kim Montagnino, company spokeswoman, said in an emailed statement. “This conclusion is aligned to the decades of clinical evidence and scientific studies by medical experts around the world that support the safety of Johnson’s Baby Powder.’’
Blinkinsop’s attorney said he was shocked and disappointed by the verdict.
“Given the hundreds of positive historical tests from J&J showing asbestos in its talc containing baby powder, as well as J&J’s ongoing decision to use deceptive testing techniques that allow for false negative results — we have no doubt asbestos was, and currently still is in J&Js talc baby powder products,” Bratt said in a statement. “Asbestos in baby powder is a huge public health concern that is far bigger than just this case.”
The company’s record at trial has been mixed so far. The company lost a $29 million jury award in a California mesothelioma case March 13 and won a defense verdict in a New Jersey trial March 27, the same day it settled the three cases.
Litigation Tourism Suffers Blow as J&J Dodges Trial in St. Louis
Several of the first trials resulted in plaintiffs’ verdicts, including one for $4.69 billion in St. Louis in 2018 to 22 women with ovarian cancer. But J&J has been able to win reversals of three of the first five jury awards.The company has also won other defense verdicts in cases alleging links between baby powder and mesothelioma beyond the New Jersey trial.
Some of the verdicts include awards against J&J’s talc supplier, Imerys America, which filed for bankruptcy protection in February.
Lawyers for Blinkinsop and his wife Karen alleged that J&J knew for decades that its talc contained asbestos yet didn’t warn or protect customers. People at J&J “made some really poor decisions in the past,’’ which led to Blinkinsop’s exposure to asbestos, Bratt said. Talc and asbestos were found in Blinkinsop’s lung tissue, he said.
Blinkinsop’s condition is “terminal,’’ he testified at trial. “It’s not curable,’’ he said. The doctors have “all said the same thing that if everything goes well, I might survive three years,’’ he told jurors. “Never any guarantee about the quality of life during that time.’’
The company’s attorney told jurors here is no asbestos in J&J talc products and its talc didn’t cause Blinkinsop’s illness. “For over 40 years we have been working with the best scientists, the best universities and the best laboratories who have all confirmed our products do not contain asbestos,’’ defense attorney Bruce Hurley said.
Blinkinsop could have been exposed to asbestos while working on construction jobs, he said.
“Mr. Blinkinsop’s mesothelioma was not cause by Johnson’s baby powder,’’ Hurley said. “Cosmetic talc does not cause mesothelioma.’’
https://www.ocregister.com/2019/04/05/jj-wins-trial-over-california-mans-talc-cancer-claim/

Ill. Medicaid to begin covering sex reassignment surgeries

Gov. J.B. Pritzker has ordered the state’s Medicaid program to begin covering the costs of sex reassignment surgeries for transgender people.
The Illinois Department of Healthcare and Family Services will develop administrative rules to offer coverage to people diagnosed with gender dysphoria to pay for genital and breast-related surgeries.
“Healthcare is a right, not a privilege, and I’m committed to ensuring our LGBTQ community and all Illinoisans have access to that right,” said Pritzker. “Expanding Medicaid to cover gender affirming surgeries is cost effective, helps avoid long term health consequences, and most importantly is the right thing to do. With continued attacks coming from Washington, this administration will always stand with our transgender community and their right to lead safe and healthy lives.”
The department said paying for the surgeries will help stave off negative health effects, such as depression and suicide. The HFS said 17 states and Washington, D.C. offer coverage for the surgeries without a significant cost increase.
The ACLU of Illinois hailed the decision to cover sex reassignment surgeries.
“We welcome Governor Pritzker’s announcement that Illinois will cover gender affirming surgery under its Medicaid program. This is a crucial step to respond to the health care needs of all Illinois residents, including those who are transgender,” said John Knight, LGBTQ and HIV Advocacy Director for the ACLU of Illinois. “By putting an end to this outdated exclusion on gender affirming surgery, Illinois now joins a long and growing list of states providing coverage for this critical, life-saving health care. We applaud the Governor for making this important step forward.”
The rule is likely to go into effect this summer.

Amgen: New Data on Osteoporosis Treatment Gap In Europe

Amgen (NASDAQ:AMGN) today announced new data presented from a cross-sectional study revealing a gap in the diagnosis and treatment of osteoporosis in Europe. The real-world study of osteoporosis management in primary care revealed that 75 percent of female patients aged 70 years and older who were at increased risk of fragility fractures were not treated for osteoporosis. The treatment gap was much lower in those with a recorded diagnosis of osteoporosis than in those without a recorded diagnosis. The results of the study, which was performed across eight European countries, were presented during the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO), in Paris from April 4-7, 2019.
“This study assessed patterns of real-world osteoporosis diagnosis and medical treatment in the European primary care setting,” said Eugene McCloskey, M.D., FRCPI, Professor of Adult Bone Diseases at The University of Sheffield and Director of the MRC Arthritis Research UK Centre for Integrated Research in Musculoskeletal Ageing. “Based on the results, future strategies need to increase awareness and facilitate the diagnosis of patients at risk in order to improve the treatment of osteoporosis and prevent fragility fractures from happening.”
The study enrolled 3,798 women aged 70 years or older after spontaneously visiting their primary care physician for any reason, not specifically related to their bone health. The primary outcome of the study was to assess the proportion of patients at increased risk of fragility fracture who were not receiving osteoporosis medication. Nearly 55 percent (n=2,077/3,798) of patients were considered to be at increased risk of fragility fracture, with 75 percent (n=1,550/2,077) of them not being medically treated for osteoporosis. Further, the study showed that among these untreated patients at risk for fracture, 85 percent (n=1,318/1,550) had no recorded diagnosis of osteoporosis.
“This real-world study further proves that an underdiagnosis of osteoporosis in Europe is a major barrier to treatment,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “The finding that the vast majority of patients at increased risk of fracture remain untreated underscores the drastic need for better osteoporosis management and reinforces our ongoing commitment to help address this worldwide public health crisis1 and improve the care for millions of people living with this disease.”

FDA moves to curb insulin prices as pressure on manufacturers mounts

Insulin manufacturers have long been criticized for raising their list prices year after year. Now the FDA aims to make it easier to compete.

As insulin manufacturers and pharmacy benefit managers (PBM) face increasing pressure over rising list prices for the drugs millions of diabetics need to survive, the Food & Drug Administration has a plan to curb costs by spurring competition.
Insulin products have been approved as drugs under the Federal Food, Drug, and Cosmetic Act, but the FDA wants to transition insulin to an abbreviated approval pathway for licensure as biologics under the Public Health Service Act in 2020. This transition for insulin and certain other biologics follows congressional intent behind the Biologics Price Competition and Innovation Act (BPCI Act)—which was passed as part of the Affordable Care Act in 2010—outgoingFDA Commissioner Scott Gottlieb, MD, said Tuesday.
“The transition of insulin from the drug to the biologics pathway will open up these products to biosimilar competition,” Gottlieb said in a statement. “We’re already seeing robust activity among sponsors seeking to bring forward biosimilar copies of insulin.”
“Once an interchangeable insulin product is approved and available on the market, it can then be substituted for the reference product at the pharmacy, potentially leading to increased access and lower costs for patients,” Gottlieb added. “The FDA anticipates that biosimilar and interchangeable insulin products will bring the competition that’s needed to help bring affordable treatment options to patients.”

Insulin manufacturers have long been criticized for raising their list prices year after year. Eli Lilly & Co.’s popular fast-acting insulin product Humalog had a list price of about $21 per vial when it first came to market in 1996, but that price rose incrementally over the years, to nearly $100 in 2009, then $275 last year, as Kaiser Health News reported.
Lilly said last month that it will offer a half-price authorized generic version of Humalog for $137.35 per vial—a move that Mayo Clinic hematologist Vincent Rajkumar, MD, and others have described as a gesture made for the sake of public relations.
PBMs, too, have taken action to address the public outcry. Cigna’s Express Scripts, one of the nation’s largest PBMs, said Wednesday it will give clients the option to limit monthly out-of-pocket insulin costs at $25 per month, as The Wall Street Journal‘s Joseph Walker reported. The move comes as the Trump administration has blamed PBM middlemen for a chunk of the high cost of U.S. healthcare.
Amid all of this, the FDA said Tuesday that it will host a public hearing May 13 to discuss insulin’s affordability and the plan to transition to a biosimilar evaluation and approval process.
“We understand the urgent need to address the high prices and lack of competition in the insulin market,” Gottlieb said.
“A drug that’s nearly a century old should not have a list price that increases between 15-17% annually,” he added. “American patients who rely on insulin to live deserve to have high-quality, affordable options.”

Exemptions surge as parents, doctors do ‘Hail Mary’ around vaccine laws

Parents have found end runs around the new law requiring vaccinations. And they have done so, often, with the cooperation of doctors — some not even pediatricians.


KEY TAKEAWAYS

California law bars parents from citing personal or religious beliefs to avoid vaccinating their children. Children could be exempted only on medical grounds.
Doctors have broad authority to grant medical exemptions to vaccination, and to decide the grounds for doing so.
Some doctors are wielding that power liberally and sometimes for cash: signing dozens — even hundreds — of exemptions for children in far-off communities.

At two public charter schools in the Sonoma wine country town of Sebastopol, more than half the kindergartners received medical exemptions from state-required vaccines last school year. The cities of Berkeley, Santa Cruz, Nevada City, Arcata and Sausalito all had schools in which more than 30% of the kindergartners had been granted such medical exemptions.
Nearly three years ago, with infectious disease rates ticking up, California enacted a fiercely contested law barring parents from citing personal or religious beliefs to avoid vaccinating their children. Children could be exempted only on medical grounds, if the shots were harmful to health.

Yet today, many of the schools that had the highest rates of unvaccinated students before the new measure continue to hold that alarming distinction. That’s because parents have found end runs around the new law requiring vaccinations. And they have done so, often, with the cooperation of doctors — some not even pediatricians. One prolific exemption provider is a psychiatrist who runs an anti-aging clinic.
Doctors in California have broad authority to grant medical exemptions to vaccination, and to decide the grounds for doing so. Some are wielding that power liberally and sometimes for cash: signing dozens — even hundreds — of exemptions for children in far-off communities.
“It’s sort of the Hail Mary of the vaccine refusers who are trying to circumvent SB 277,” the California Senate bill signed into law by Gov. Jerry Brown in 2015, said Dr. Brian Prystowsky, a Santa Rosa pediatrician. “It’s really scary stuff. We have pockets in our community that are just waiting for measles to rip through their schools.”
The number of California children granted medical exemptions from vaccinations has tripled in the past two years.
Across the nation, 2019 is shaping up to be one of the worst years for U.S. measles cases in a quarter-century, with major outbreaks in New York, Texas and Washington state, and new cases reported in 12 more states, including California. California’s experience underlines how hard it is to get parents to comply with vaccination laws meant to protect public safety when a small but adamant population of families and physicians seems determined to resist.
When Senate Bill 277 took effect in 2016, California became the third state, after Mississippi and West Virginia, to ban vaccine exemptions based on personal or religious beliefs for public and private school students. (The ban does not apply to students who are home-schooled.)
In the two subsequent years, SB 277 improved overall child vaccination rates: The percentage of fully vaccinated kindergartners rose from 92.9% in the 2015-16 school year to 95.1% in 2017-18.
But those gains stalled last year due to the dramatic rise in medical exemptions: More than 4,000 kindergartnersreceived these exemptions in the 2017-18 school year. Though the number is still relatively small, many are concentrated in a handful of schools, leaving those classrooms extremely vulnerable to serious outbreaks.
Based on widely accepted federal guidelines, vaccine exemptions for medical reasons should be exceedingly rare. They’re typically reserved for children who are allergic to vaccine components, who have had a previous reaction to a vaccine, or whose immune systems are compromised, including kids being treated for cancer. Run-of-the-mill allergies and asthma aren’t reasons to delay or avoid vaccines, according to the U.S. Centers for Disease Control and Prevention. Neither is autism.
Before California’s immunization law took effect, just a fraction of 1% of the state’s schoolchildren had medical exemptions. By last school year, 105 schools, scattered across the state, reported that 10% or more of their kindergartners had been granted medical exemptions. In 31 of those schools, 20% or more of the kindergartners had medical exemptions.

SEESAWING EXEMPTIONS

As of July 2016, California no longer allows parents to exempt their children from state-required vaccinations based on personal beliefs. Many of the same schools that once had the highest percentage of students with personal belief exemptions now lead the state in student medical exemptions.
The spike in medical exemptions is taking place amid a politically tinged, often rancorous national conversation over vaccines and personal liberty as measles resurges in the U.S. and worldwide. At least 387 cases of measles had been reported nationwide through March 28, according to the CDC. In California, 16 cases had been reported, two of them requiring hospitalization.
The problem in California, state officials say, is how the immunization law was structured. It removed the ability of parents to cite “personal belief” as a reason for exempting their children from vaccine requirements in day care and schools. Exemptions now must be authorized by a licensed physician who provides a written statement citing a medical condition that indicates immunization “is not considered safe.”
But the law does not specify the conditions that qualify a student for a medical exemption, nor does it require physicians to follow federal guidelines.
The wording has led to a kind of gray market in which parents share names of “vaccine-friendly” doctors by word of mouth or in closed Facebook groups. And some of those doctors are granting children blanket exemptions — for all time and all vaccines — citing a range of conditions not supported by federal guidelines, such as a family history of eczema or arthritis.
Amid growing concerns about suspect exemptions, the California Department of Public Health recently launched a review of schools with “biologically unlikely” numbers of medical exemptions, said the agency’s director, Dr. Karen Smith. Doctors who have written questionable exemptions will be referred to the Medical Board of California for possible investigation.
The medical board, which licenses doctors, has the authority to levy sanctions if physicians have not followed standard medical practice in examining patients or documenting specific reasons for an exemption.
In recent years, however, the board has sanctioned only one doctor for inappropriately writing a medical vaccine exemption in a case that made headlines. Since 2013, the board has received 106 complaints about potentially improper vaccine exemptions, including nine so far this year, said spokesman Carlos Villatoro.
One pending case involves Dr. Ron Kennedy, who was trained as a psychiatrist and now runs an anti-aging clinic in Santa Rosa.
Medical board investigators took the unusual step of subpoenaing 12 school districts for student medical records after receiving complaints that Kennedy was writing inappropriate exemptions. They found that Kennedy had written at least 50 exemptions, using nearly identical form letters, for students in multiple communities, including Santa Rosa, Fremont and Fort Bragg, saying that immunizations were “contraindicated” for a catchall list of conditions including lupus, learning disability, food allergies and “detoxification impairment.”
Dr. Dean Blumberg, chief of pediatric infectious diseases at UC Davis Children’s Hospital and the medical board’s expert witness, said that the exemptions issued by Kennedy appear to have been provided “without an appropriate evaluation,” according to court documents.
Kennedy has refused to respond to the board’s subpoenas seeking the medical records of three of his patients, according to court documents. The board has yet to file a formal accusation against Kennedy, and he continues to practice.
Like Kennedy, many of the doctors granting unorthodox exemptions cite their belief in parental rights or reference concerns not supported by conventional medical science. Kennedy is suing the medical board and its parent agency, the California Department of Consumer Affairs, saying the state did not have the legal right to subpoena school districts for his patients’ medical records without first informing him so he could challenge the action in court. The case is ongoing.
Kennedy declined comment to Kaiser Health News. “I don’t want to be out in the open,” he said in a brief phone exchange. “I’ve got to go. I’ve got a business to run.”
In Monterey, Dr. Douglas Hulstedt is known as the doctor to see for families seeking medical exemptions. In a brief phone interview, he said he was worried about being targeted by the state medical board. “I have stuck my neck way out there just talking with you,” he said. Hulstedt does not give exemptions to every child he examines, he said, but does believe vaccines can cause autism — a fringe viewpoint that has been debunked by multiple studies.
In March, the online publication Voice of San Diego highlighted doctors who write medical exemptions, including one physician who had written more than a third of the 486 student medical exemptions in the San Diego Unified School District. District officials had compiled a list of such exemptions and the doctors who provided them.
State Sen. Richard Pan (D-Sacramento), a pediatrician who sponsored California’s vaccine law, has been a vocal critic of doctors he says are skirting the intent of the legislation by handing out “fake” exemptions. Last month, he introduced follow-up legislation that would require the state health department to sign off on medical exemptions. The department also would have the authority to revoke exemptions found to be inconsistent with CDC guidelines.
“We cannot allow a small number of unethical physicians to put our children back at risk,” Pan said. “It’s time to stop fake medical exemptions and the doctors who are selling them.”