BrainStorm Succeeds on Safety Analysis in Phase 3 ALS Therapy Trial

BrainStormCell Therapeutics Inc., (NASDAQ:BCLI), a leading developer of adult stem cell therapies for neurodegenerativediseases, today announced that the independent Data Safety Monitoring Board (DSMB) has completed the pre-specified interim analysis of safety outcomes for the first 31 participants treated with NurOwn in the Phase 3 trial in ALS (NCT03280056). The DSMB indicated there were no significant safety concerns and recommended that the trial continue, as planned.

The DSMB appreciates the continued commitment of Brainstorm and the research teams to conducting this trial in such an exemplary manner, said Carlayne Jackson MD, DSMB Chairperson, We commend them on their outstanding enrollment and the quality of data collection.

BrainStorm is conducting a repeat dose US Phase 3 trial of NurOwn for ALS participants at 6 US sites, supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The study is expected to enroll 200 ALS participants, randomized 1:1 to NurOwn or placebo, and is evaluating the ALS functional rating scale (ALSFRS-R) as the primary efficacy outcome measure, 28 weeks after the first of three NurOwn intrathecal treatments.

To date, 82 participants have been enrolled in the trial, with 61 currently active. Many of the active participants have received two intrathecal treatments, with some completing all three. The Company anticipates that 110 participants in total will be enrolled in the trial by January 2019. Given the current pace of enrollment, we anticipate completing enrollment by mid 2019, which would then put us in a position to file a Biologics License Application for US FDA approval, once all clinical trial evaluations are completed.

BrainStorm is focused on completing the NurOwn ALS Phase 3 study and to bringing a much needed treatment option to ALS patients, said ChaimLebovits, president and CEO ofBrainStorm, We welcome the DSMBs review which confirms the safety profile of NurOwn following repeat dose intrathecal administration.

Ralph Kern MD, MHSc, Chief Operating Officer and Chief Medical Officer of BrainStorm said, “We are very pleased the DSMB has found no safety concerns that would require modification to the NurOwn ALS Phase 3 protocol. This represents an important clinical advancement for BrainStorm and for NurOwn as a viable cellular therapy approach for ALS patients.

https://bit.ly/2BKNRuV

Esperion has Phase 3 results for cardiology confab session

— Bempedoic Acid Achieved Additional 20% On-Treatment LDL-C Lowering on Background of Maximally Tolerated Statins —

— Study 1 (CLEAR Harmony) Provided the Largest Evidence to Date that Bempedoic Acid Is Safe when Added on to Maximally Tolerated Statins —

— Bempedoic Acid Provides Additional Oral Therapeutic Option to Safely Lower LDL-C in High-Risk ASCVD Patients Treated with Statins —

Esperion (NASDAQ:ESPR) today announced that the final results from the pivotal Phase 3 Study 1 (1002-040 or CLEAR Harmony) were presented at the European Society of Cardiology (ESC) Congress in Munich, Germany. This Phase 3 study evaluated the long-term safety, tolerability and efficacy of bempedoic acid 180 mg versus placebo in high-risk patients with atherosclerotic cardiovascular disease (ASCVD) who are inadequately controlled with current lipid-modifying therapies, including maximally tolerated statins. The late-breaking oral presentation was delivered by Professor Kausik K. Ray, MBChB, MD, MPhil, Professor of Public Health at the School of Public Health, Imperial College London and a Consultant Cardiologist. Topline results were announced earlier this year in May.

“The final data from Study 1 provide greater reassurance about the safety of bempedoic acid and reconfirm the efficacy over a longer period of time,” said Professor Ray.  “Our findings – supported by other ongoing bempedoic acid studies – may very soon offer clinicians an additional oral lipid lowering agent with which to treat high-risk patients.”

New data presented today as part of the final Study 1 results showed patients on bempedoic acid who were on a maximally tolerated statin dose had significantly fewer instances of new-onset or worsening diabetes than those on placebo who were on a maximally tolerated statin dose (5.4 percent compared to 3.3 percent; p<0.02).  In addition, serious AEs, including neoplasms, were balanced between the two study arms.  A detailed listing of all adjudicated cardiovascular events was provided, again showing balance between the two study arms.

https://bit.ly/2MQPfR2

Adverum Gets Orphan Drug Tag for Angioedema Gene Therapy Candidate

Adverum Biotechnologies, Inc. (Nasdaq:ADVM), a clinical-stage gene therapy company targeting unmet medical needs in serious rare and ocular diseases, today announced that the United States (U.S.) Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ADVM-053, a preclinical gene therapy candidate being investigated as a potential singleadministration treatment which has the potential to provide sustained levels of the C1 esterase inhibitor (“C1EI”) protein.

HAE affects approximately 8,000 individuals in the U.S. This disease is caused by a genetic mutation that results in low levels of C1 esterase inhibitor which can be associated with sudden swelling and edema of respiratory airways, gastrointestinal tract, and extremities.

“We are pleased to receive the Orphan Drug Designation for ADVM-053 from the FDA,” said Leone Patterson, interim president and chief executive officer of Adverum Biotechnologies. “We are committed to developing effective treatments for patients living with HAE and the support from the FDA will be invaluable towards this goal. We look forward to submitting our IND application in the fourth quarter.”

https://bit.ly/2Ni6uYA

Sun Pharma gets final USFDA approval for generic Aggrenox

Sun Pharma has received final USFDA approval for Aspirin and Dipyridamole. This is a generic copy of Boehringer Ingelheim Pharmas drug Aggrenox, which is used to lower the risk of stroke in people who have had a mini-stroke or stroke due to a blood clot.

Teva launched the generic of this drug in July 2015 and there are six more generic companies who have final USFDA approval to make copy of this drug (Sandoz, Barr, Par, Cadila, Amneal and ANI pharma). Sun will become eighth generic manufacture.

Aggrenox and its generics are estimated to have US sales of ~$230mn in the US and with the lower competition, we expect Sun to make $8-10mn/annum from this drug.

https://bit.ly/2MwLjW9

EpiPen Shortage Hits Back-to-School Season

Parents are scrambling to find pharmacies carrying EpiPens for the new school year as regulators and the drug’s manufacturer struggle to abate a continuing global shortage of the lifesaving devices.

EpiPens, the emergency epinephrine treatment for allergic reactions, have been in short supply since at least May, when the U.S. Food and Drug Administration first declared a shortage. Some pharmacies around the country have been unable to restock the medication for weeks at a time because of the shortages.

A rival epinephrine injector product, a generic version of Adrenaclick made by Amneal Pharmaceuticals Inc., is also in short supply, according to the FDA. That product is manufactured at a different Pfizer plant in Kansas, where production delays have caused shortages since the first quarter of the year, an Amneal spokesman said.

The scarcity is being felt more acutely now amid the back-to-school rush of August and September when demand for the devices is highest. For parents of children with food allergies, refilling EpiPen prescriptions, which are typically for sets of two in case the first injection doesn’t work, has become part of the annual back-to-school ritual.

Julie Cook has been unable to fill EpiPen prescriptions for her two teenagers since the beginning of August and is relying on a single unexpired set if one of them has an allergic reaction. When she called a Walgreens near her Wheaton, Ill., home a few days ago, the pharmacist said they may not have more until September.

On the first day of school this week, Ms. Cook split the unexpired EpiPen set and gave one injector each to her children. As a backup, she also gave each an old, expired injector from among the dozen or so she keeps just in case.

“It’s so frustrating,” Ms. Cook said. “Why is this happening in August? What’s going on? And what’s going to happen in the future?”

EpiPens are sold by Mylan NV and manufactured at a Pfizer Inc.-owned plant in Brentwood, Mo. Pfizer has been unable to make enough EpiPens because it is changing its manufacturing processes in response to an FDA inspection last year that found several violations, including a failure to investigate serious complaints about product quality. In a statement, Pfizer said, “We are working tirelessly to increase production and expedite shipments as rapidly as possible.”

Mylan referred questions about manufacturing delays to Pfizer. In a statement earlier this month, the company encouraged patients to call its customer service hotline for assistance in locating pharmacies with EpiPens in stock.

Rajiv Malik, Mylan’s president, said on an earnings call with analysts earlier this month that “Pfizer supplies to Mylan are inconsistent and inadequate in meeting global demand.” There are months where supply from Pfizer is good, and “then suddenly we get very erratic,” and supply is 30% to 40% off expectations “because of the quality issues,” Mr. Malik said, according to a transcript.

To help alleviate the effects of the shortage, the FDA on Tuesday extended the expiration date for certain EpiPen lots for an additional four months. The devices typically have a shelf life of 20 months, the agency said. The FDA has also been in touch with manufacturers of rival products to help ensure alternatives are available, the agency said.

Kaleo, the privately held maker of the Auvi-Q epinephrine injectors, has significantly increased manufacturing capacity to help meet demand in the U.S. and Canada due to the EpiPen shortage, said Kaleo CEO Spencer Williamson in an interview. Some 40% of all epinephrine injectors are purchased during the back-to-school season, he said.

However some patients have said they are reluctant to use Auvi-Q because it isn’t covered under their insurance or because it has a different mechanism that they and their children aren’t used to.

Patient access to EpiPens has been a controversial issue since the summer of 2016, when parents looking to buy the devices for their school-age children complained they had to pay hundreds of dollars out of pocket to meet insurance deductibles. Congress began scrutinizing Mylan for raising the list price of EpiPen 548% over several years to about $608 for a set of two. Mylan later began selling its own generic version of EpiPen for $300.

Earlier this month, the FDA approved the first generic EpiPen from a rival, which the agency said was part of an effort to inject more competition into the pharmaceutical industry and bring down prices. But Teva Pharmaceutical Industries Ltd., which will market the generic version in the U.S., said the product would be launched in “coming months.” Antares Pharma Inc., which is manufacturing the injection device for Teva’s generic, said the delay wasn’t due to manufacturing constraints on its part and that it has already shipped $22 million of product to Teva.

Meanwhile, Mylan issued a nationwide recall last year of certain EpiPen lots because of a potential manufacturing defect that could cause the devices to fail to activate. In a letter to Pfizer last year, the FDA admonished the company for “not thoroughly investigat[ing]” hundreds of complaints it received, stating that “EpiPen products failed to operate during life-threatening emergencies, including some situations in which patients subsequently died.”

Pfizer said in a statement that “there is no information to show that there was any causal connection between complaints of product failure and any patient deaths.”

Rosvold Pharmacy in Cinnaminson, N.J., hasn’t received an EpiPen shipment since July 19, said owner Thomas E. Stehr. The pharmacy tries to order more every day, but it is still on back-order, he said. “We have a pretty good school-age population here,” and “the parents start freaking out” when they can’t get EpiPens, Mr. Stehr said.

Wegmans Food Markets Inc., an East Coast supermarket chain, said its pharmacies’ supply of EpiPens has been spotty since April, and some of its stores have extremely limited quantities. A significant share of EpiPen prescriptions are filled between July and September, according to a Wegmans spokeswoman. To meet demand, the company will move product between stores or refer patients to another location, she said.

Tory Palenscar tried in early August to fill EpiPen prescriptions for her 7-year-old daughter, who suffers from severe food allergies. Her daughter’s school wants her to have four sets.

But there were no EpiPens at any pharmacy near Ms. Palenscar’s home in Beaumont, Calif. “I started panicking,” she said. Finally, Ms. Palenscar found a pharmacy 30 minutes away in San Bernardino that agreed to hold one set for her, but she is still waiting to buy more. She used a voucher from Mylan to cover the prescription’s $170 copay, she said.

She and her husband are keeping the new EpiPen set in an emergency bag. Ms. Palenscar also obtained two sets of Auvi-Q, which Kaleo provided to her free of charge because her insurance policy doesn’t cover the product. She has given the Auvi-Q injectors to her daughter’s school, along with two expired EpiPen sets.

“There’s been so many recalls and overcharging. It’s one thing after another, and it feels like we’re being taken advantage of and played with,” Ms. Palenscar said. “This is my daughter’s life.”

https://bit.ly/2BMc58h

Caring for Aging Parents, With an Eye on the Broker Handling Their Savings

Tracey Dewart faced a daunting task last summer: moving her 84-year-old mother, Aerielle, from her Manhattan apartment to an assisted living facility in Brooklyn. Her mother, who has Alzheimer’s, didn’t want to go, but there was little choice after she was found wandering near her home on the Upper East Side several times.

It was “physically and emotionally a horrible and overwhelming time,” said Ms. Dewart, 58. “It felt like there had been a death in the family as we had to sort through all of my parents’ belongings.”

And she was about to confront another ordeal — one that could serve as a cautionary tale for anyone who helps manage their parents’ money and, more broadly, anyone who does business with an investment broker.

To help pay for her mother’s care, Ms. Dewart relied on an investment account at J.P. Morgan Securities that her 89-year-old father, Gordon, opened at least eight years ago. The account was already paying expenses for Ms. Dewart’s father — who, after two strokes, was living in the residence that his wife was moving to — and for Ms. Dewart’s younger sister, who lives in a community for adults with developmental disabilities.

Around the time of her mother’s move, Ms. Dewart noticed what looked like unusual activity in the account, which she and her older sister had overseen for about four years. A closer look revealed that it was down $100,000 in a month.

“My own accounts were rallying, so I thought this was strange,” she said.

She notified the firm that something seemed awry. As someone who does research and policy analysis for a living, she also put her own skills to work.

She pored over piles of statements and trade confirmations, built spreadsheets and traded phone calls and emails with the broker who handled the account, Trevor Rahn, his manager and the manager’s manager. She hired a lawyer and worked with a forensic consultant.

After about six months, she learned that the account, worth roughly $1.3 million at the start of 2017, had been charged $128,000 in commissions that year — nearly 10 percent of its value, and about 10 times what many financial planners would charge to manage accounts that size.

In August 2017 alone, Mr. Rahn had sold two-thirds of the portfolio, or about $822,000, and then reinvested most of the proceeds, yielding about $47,600 in commissions, according to monthly financial statements and an analysis by Genesis Forensic Consulting, the firm Ms. Dewart’s lawyer hired.

A statement listed all 344 trades that month as “unsolicited” — meaning, in Wall Street terms, that they were the customer’s idea, not the broker’s. But Ms. Dewart said she had not authorized the transactions and had only discussed a few specific ideas with Mr. Rahn, including possibly selling some Exxon shares if cash was needed.

An August 2017 statement showed that the Dewarts’ portfolio was down about $100,000 in a month and that roughly two-thirds of the stocks in it had been sold in that time.

Something else was unusual. Mr. Rahn was selling stocks in small batches multiple times a day. In April 2017, he sold between 75 and 125 shares of Exxon eight times in one day, rather than all at once, generating commissions on each sale.

“These are not just bad choices,” said Laura Levasseur, the president of Genesis Forensic. “This is frantic trading.”

Ms. Dewart also discovered that the Exxon stock and other investments were being held in a margin account, which lets customers use borrowed shares to make bigger bets, potentially amplifying gains and losses. She said she never approved opening such an account.

“I had implicitly trusted Trevor because my father did,” she said. Her father had first put his investments in Mr. Rahn’s care when the broker was at Deutsche Bank, and had followed him to J.P. Morgan in 2010.

About five months after Ms. Dewart questioned Mr. Rahn’s handling of the account, J.P. Morgan had canceled 681 of the 1,499 transactions for 2017, crediting about $84,000 in commissions, according to Genesis. That left 818 trades and commissions totaling about $44,000 for the year — about 3.8 percent of the account’s value, still triple what many financial planners would charge.

Ms. Dewart considered taking J.P. Morgan to arbitration as allowed by the customer agreement, but she settled instead for a sum that she is prohibited from discussing.

In a statement, J.P. Morgan said, “The client agreed to an appropriate resolution of this matter in June.” The firm said it was committed to doing the right thing for its clients, and was “disappointed when any feel their expectations haven’t been met.”

Mr. Rahn, who still works at J.P. Morgan, and the two managers at the firm with whom Ms. Dewart dealt did not respond to emails seeking comment.

Ms. Dewart’s experience leaves many questions unanswered. Her broker was not authorized to trade without permission, so why did he? Why was such a large stock sold in so many small transactions? Were other customers subject to similar trading activity? She said a firm manager told her that there had been a system error — what kind?

The episode also underscores the murky regulatory territory that brokers inhabit. They are not necessarily fiduciaries, meaning they do not always have to act in a client’s best interest. Instead, brokers typically only have to recommend investments that are “suitable,” a lower standard.

Ms. Dewart said Mr. Rahn’s supervisor had told her that “any transaction the adviser does is meant to be done with the client’s knowledge,” but that had not happened.

The Dewarts’ customer agreement with J.P. Morgan Securities stated that the firm was not acting as a fiduciary, providing advice or acting as an adviser.

“I knew that I did not know enough about equities to sign off on a massive restructuring,” she said. “And he restructured twice.”

Excessive and unauthorized trading are among the top complaints in customer arbitration cases, according to the Financial Industry Regulatory Authority, or Finra. Just last year, the Securities and Exchange Commission issued an alert about churning, a term for excessive trading, to help investors identify warning signs.

There were 166 cases of unauthorized trading in 2017, 209 in 2016 and 145 in 2015, Finra said. There were 142 complaints for excessive trading in 2017.

Because Ms. Dewart settled her case, it was not included in last year’s count, suggesting that Finra’s statistics understate the number of complaints raised with brokerage firms. And many investors who settle such cases sign confidentiality clauses, securities lawyers said. (Ms. Dewart said she was unable to speak about the terms and conditions of her settlement.)

Commission-based accounts like the one Ms. Dewart had can be economical for investors who don’t require many changes to their portfolios. But because brokers are only paid each time they conduct a transaction, their interests are not necessarily aligned with those of their clients.

Big brokerage and financial services firms have been shifting to accounts that charge a flat annual fee for management services, reducing the potential for conflicts of interest.

The shift accelerated in anticipation of a consumer-protection rule crafted by the Department of Labor during the Obama administration that required all financial professionals to put their customers’ interests ahead of their own, at least when handling retirement accounts. Merrill Lynch went as far as banning commission-based retirement accounts. The rule was struck down by a federal appeals court in June, and Merrill has said it was considering reversing that policy.

In April, the S.E.C. proposed a new rule that it said would require brokers to put their clients’ interests first. Consumer advocates have come out against the proposal, arguing that it does not go far beyond what is already required of brokers.

“If the rule did what they say it does, we’d support it,” said Barbara Roper, director of investor protection at the Consumer Federation of America. “But it just flat doesn’t.”

A stronger rule may not have helped Ms. Dewart, but she said the current structure was stacked against consumers.

“There is a point,” she said, “where, out of sheer exhaustion, people surrender to the system.”

Morgan Stanley warns of momentum in hospital closings

While the stock market could indeed be in the most extended bull market in history, there are new, troubling signs that the real economy is faltering.

A new report has sounded the alarm about the pace of hospital closures across the country. It says there are several factors pressuring margins at hospitals that are contributing to the accelerating rate of closures, particularly in rural communities.

The American Hospital Association (AHA) conducts an annual survey of hospitals in the United States. The data shows hospitals have been closing at a rate of about 30 per annum.

Bloomberg spoke with Morgan Stanley analysts led by Vikram Malhotra, who examined data from roughly 6,000 US private and public hospitals and determined eight percent are at risk of closing; another 10 percent are considered extremely “weak.” Malhotra defined weak hospitals based on criteria for margins for earnings before interest and other items, occupancy and revenue. The “at risk” group was defined by capital expenditures and efficiency, among others.

In a phone interview with Bloomberg, Malhotra warned about the next wave of hospital closings that could be triggered in the next 6 to 18 months.

“The risks are coming following years of mergers and acquisitions. The most recent deal saw Apollo Global Management LLC swallowing rural hospital chain LifePoint Health Inc. for $5.6 billion last month. Apollo declined to comment on the deal; LifePoint has until Aug. 22 to solicit other offers. Consolidation among other health-care players, such as CVS’s planned takeover of insurer Aetna Inc., could also pressure hospitals as payers push patients toward outpatient services.

There are already a lot of hospitals with high negative margins, consultancy Veda Partners health care policy analyst Spencer Perlman said, and that’s going to become unsustainable. Rural hospitals with a smaller footprint may have less room to negotiate rates with managed care companies and are often hobbled by more older and poorer patients,” said Bloomberg.

Rural Hospital Closures Since 2010

There have been 83 rural hospital closures since 2010 and 125 since 2005, according to a new infographic by Stroudwater. The infographic breaks down the hospitals’ Medicare payment type, location, whether or not the hospitals are located in a Medicaid expansion state and the closure year (Source/ Melanie Matthews)

Bloomberg Intelligence analyst Jason McGorman said margin compression is also occurring as technological improvements allow patients to get more surgeries and imaging done outside of the hospital.

They “are getting eaten alive from these market trends,” Perlman cautioned.

“Future M&A options could be too late – buyers may hesitate as debt-laden operators like Community Health Systems Inc. and Tenet Healthcare Corp. focus on selling underperforming sites to reduce leverage,” Morgan Stanley’s Zachary Sopcak said.

Some facilities are restructuring as outpatient emergency clinics with free-standing emergency departments. “Microhospitals,” or facilities with ten beds or less, seems to be gaining a foothold across the country. They have been springing up as of late in multiple states, including Texas, Colorado, Nevada, and Arizona. Dignity Health, a health system with facilities in Nevada, Arizona, and California, is also considering the possibility of testing the model in California, Kaiser Health News reports.

As for the incoming wave of hospital closures that Morgan Stanley expects to hit in the near term, well, it is more bad news for rural America that seems to have been left out of the “greatest economy ever.”

https://bit.ly/2wqBLRR