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Saturday, October 6, 2018

VistaGen Gets Fast Track, Other Drugmakers Advance Non-Opioids


Opioids have shown tremendous efficacy in pain management. At the same time, the dangers of the addiction to the medication have become well-known in recent years as an epidemic has swept across the United States.
Last week, a pharmacist in Illinois warned me of the dangers of opioids as he filled a prescription for hydrocodone following a minor surgery. The pharmacist recommended taking acetaminophen for pain instead of the hydrocodone if that was possible – it was.
According to the National Institutes of Health, about 115 Americans die daily from overdosing on opioids, which includes illicit drugs, as well as prescription medications. As more and more patients, prescribers and pharmacists are recognizing the dangers of opioid-based pain medications, multiple companies are developing non-opioid treatments for pain. This week South San Francisco-based VistaGen Therapeutics snagged Fast Track designation from the U.S.Food and Drug Administration (FDA) for its neuropathic-pain candidate AV-101, the second such designation in the past year.
Neuropathic pain affects approximately 33 million people in the United States. It is characterized by a steady burning or sensation that results in abnormal neuronal function.
AV-101 is an investigational, orally bioavailable, small molecule NMDA (N-methyl-D-aspartate) receptor glycine B antagonist without psychological or sedative side effects, according to company data. In December, AV-101 was awarded the Fast Track designation for major depressive disorder. It is currently in Phase II development for that indication.
Shawn Singh, chief executive officer of VistaGen, said AV-101 has the potential to “address the high unmet need for a new non-opioid, non-sedating treatment for neuropathic pain.” He made that assertion based on peer-reviewed data published last year in The Journal of Pain coupled with data from the company’s Phase I clinical trial.
Singh pointed to the Fast Track designation awarded to AV-101 as a sign of the FDA’s commitment to addressing the opioid epidemic sweeping the nation.
“The FDA’s Fast Track designation for development of AV-101 for neuropathic pain, together with the previously granted Fast Track designation for major depressive disorder, will allow our team to work closely with the FDA to bring AV-101 to patients affected by two of our country’s most debilitating and widespread healthcare concerns as soon as possible,” Singh said in a statement.
VistaGen’s Fast Track designation comes about a month after the FDA and Commissioner Scott Gottlieb outlined plans for the regulatory agency to address opioid addiction. Part of that plan includes a new guidance to advance the development of non-addictive treatments for pain, which would include VistaGen’s AV-101, as well as other potential candidates. Earlier this year the FDA launched an “innovation challenge” to spur on the development of medical devices that can combat the crisis and help prevent and treat opioid use disorder – a disorder that is often caused by abuse of opioid-based pain treatments.
Other pharma and biotech companies are also focused on developing treatments for acute pain that do not use opioids, which BioSpace has highlighted in the past. For example, Connecticut-based Biowave’s non-opioid Smarter Pain Blocking Technology has been adopted for use by 32 veteran’s hospitals across the country. Likewise, startup Tremeau Pharmaceuticals is developing TRM-201 (rofecoxib), a highly potent cyclooxygenase-2 (COX-2) selective NSAID (nonsteroidal anti-inflammatory drugs) to treat hemophilic arthropathy (HA), a degenerative joint disease occurring in patients with hemophilia. Rofecoxib is a non-narcotic analgesic, unlike opioids, and has no effect on bleeding time relative to placebo.
Another non-opioid pain treatment in development is an NSAID spray. Pennsylvania-based Virpax Pharmaceuticals licensed MedPharm’s MedSpray ‘Patch-in-a-Can’ Technology as a non-opioid treatment for pain. The Patch-in-a-Can product, called DSF100 (NSAID spray film 1.3%), delivers an NSAID through a metered spray to the skin. The medicine is absorbed to target the pain.

Friday, October 5, 2018

Spinal implant manufacturer SI-BONE sets terms for $84 million IPO


SI-BONE, which manufactures spinal implants for the alleviation of lower back pain, announced terms for its IPO on Friday.
The Santa Clara, CA-based company plans to raise $84 million by offering 6 million shares at a price range of $13 to $15. Insiders intend to purchase up to $32 million of the IPO (38% of the deal). At the midpoint of the proposed range, SI-BONE would command a fully diluted market value of $335 million.
SI-BONE was founded in 2008 and booked $52 million in revenue for the 12 months ended June 30, 2018. It plans to list on the Nasdaq under the symbol SIBN. Morgan Stanley and BofA Merrill Lynch are the joint bookrunners on the deal. It is expected to price during the week of October 15, 2018.
Relevant Profile: SIBN

Collins defends Kavanaugh’s healthcare record, renders confirmation likely


The senator’s speech defended the nominee’s track record on the ACA and abortion, rejecting claims that confirming him could endanger legal healthcare-related legal precedent.

With a highly anticipated speech on the Senate floor Friday afternoon, Sen. Susan Collins, R-Maine, announced that she will vote in favor of Judge Brett Kavanaugh’s nomination to the U.S. Supreme Court, virtually guaranteeing that a contentious vetting process will end with Kavanaugh’s confirmation.
Due to a lack of corroborating evidence, the allegations of sexual misconduct brought against Kavanaugh did not overcome the presumption of innocence, Collins said, scolding her fellow senators for allowing the process to devolve into a partisan fight.
Collins defended the nominee’s record on a number of topics, specifically rejecting claims that confirming Kavanaugh could spell trouble for the Obama administration’s signature healthcare law and decades of legal precedent on abortion rights.
“One concern that I frequently heard was that the judge would be likely to eliminate the Affordable Care Act’s vital protections for people with preexisting conditions. I disagree with this contention,” Collins said. “In a dissent in Seven-Sky v. Holder, Judge Kavanaugh rejected a challenge to the ACA on narrow procedural grounds, preserving the law in full. Many experts have said that his dissent informed Justice Roberts’ opinion upholding the ACA at the Supreme Court.”
Roberts’ opinion upheld the ACA as constitutionally authorized by congressional power to tax. In light of the ACA’s individual mandate being zeroed out, a Texas-led coalition of conservative states has claimed that dropping the tax penalty to $0 renders the entire law unconstitutional, so they have asked a federal judge to impose an injunction. The judge, who reportedly seemed sympathetic to the plaintiffs’ argument, could rule on the request any day now, setting off a chain of appeals that could land before the Supreme Court.
Collins argued that Kavanaugh would be disinclined to overturn the ACA in its entirety because his approach to severability is narrow.
“When a part of a statute is challenged on constitutional grounds, he has argued for severing the invalid clause as surgically as possible, while allowing the overall law to remain intact,” Collins said, citing Kavanaugh’s dissent last January in PHH Corp. v. Consumer Financial Protection Bureau.
“Given the current challenges to the ACA, proponents—including myself—of protections for people with preexisting conditions should want a justice who would take just this kind of approach,” she added.

ABORTION RIGHTS

On the campaign trail, then-candidate Donald Trump promised to pick Supreme Court nominees who would overturn Roe v. Wade, the 1973 decision affirming a woman’s constitutional right to an abortion prior to a fetus achieving viability.
Collins said Friday, however, that this pledge has been part of the Republican platform in every presidential campaign since at least 1980 and that Kavanaugh views abiding by legal precedent as constitutionally required, “except in the most extraordinary of circumstances.”
“In short,” Collins said, “his views on honoring precedent would preclude attempts to do by stealth that which one has committed not to do overtly.”
The final vote is expected to take place on Saturday.

Healthcare jobs growth contributes to lowest unemployment in 49 years


The growth contributed to the unemployment rate falling to 3.7% last month.

The U.S. healthcare sector added about 26,000 jobs last month, including 12,000 associated with hospitals, according to monthly Bureau of Labor Statistics data released Friday.
The growth contributed to the unemployment rate falling from 3.9% in August to 3.7% in September. That’s the lowest unemployment rate since 1969, according to historical BLS data.
Although the report indicated that the economy added 134,000 jobs last month across all sectors, that figure fell well below expectations, falling to the slowest pace in a year, as CNBC reported. But the dampened data could be attributed in part to Hurricane Florence, as Center on Budget and Policy Priorities senior fellow Jared Bernstein wrote in a blog post Friday.
“The decline in unemployment is ‘real,’ meaning it occurred through fewer unemployed persons as opposed to people leaving the labor market,” Bernstein added.
Healthcare employment has increased by more than 300,000 jobs over the year.

HCA’s success over 50 years banks on sticking with the basics


HCA Healthcare’s recipe for success in a complex and technical industry is pretty simple. It comes down to size, deep pockets and unparalleled operational savvy.
The sheer size of Nashville-based HCA, the nation’s largest health system with 178 hospitals and thousands of other facilities, has given it an advantage over others by allowing it to spread the expense of back-office functions, the latest technology, and tasks like billing and purchasing supplies across its vast network, driving efficiency and lowering unit costs.
Size and dominant market share have enabled HCA to negotiate higher prices from health insurers. And lots of cash has allowed it to invest in the buildings, equipment, and clinical research that smaller health systems or stand-alone hospitals don’t necessarily have the capital to do.
Industry experts say that over its 50 years, HCA’s executives have also gotten really good at the day-to-day running of hospitals and understanding changes in the broader healthcare landscape. “It has to do with execution and getting the right people and executing a well-thought-out business plan, and being very entrepreneurial and flexible as the world changes,” co-founder Dr. Thomas Frist Jr. said.

Focused on growth

“It has to do with execution and getting the right people and executing a well-thought-out business plan, and being very entrepreneurial and flexible as the world changes.”
Dr. Thomas Frist Jr.
Co-founder
HCA“It has to do with execution and getting the right people and executing a well-thought-out business plan, and being very entrepreneurial and flexible as the world changes.”
Dr. Thomas Frist Jr.
Co-founder
HCAMark Mosrie
Being big was always the goal. In 1968, Frist, along with his cardiologist father, Dr. Thomas Frist Sr., and Jack Massey, the former owner of fast-food chain KFC, combined their medical expertise with business savvy to build what was then known as the Hospital Corporation of America, which has grown from a 200-bed hospital in Nashville to the behemoth it is today, representing 5%-6% of all U.S. healthcare spending, according to the company.
From the beginning, HCA grew rapidly by buying up hospitals and building new ones as demand surged on the heels of the creation of Medicare and Medicaid. It has had periods characterized by organic growth and others by fast-paced mergers and acquisitions. It has gone private and then back to public at times when valuations were most attractive. And it survived one of the industry’s largest fraud investigations to solidify its reputation as a well-oiled, well-managed corporate machine.
Its net income in 2017 totaled $2.7 billion on revenue of $43.6 billion. That year, HCA’s net patient revenue of $40.1 billion dwarfed that of not-for-profit Kaiser Foundation Hospitals, the next biggest system with net patient revenue of $21.4 billion. Its stock price has grown to nearly $140 per share from $46 five years ago.

Blocking and tackling

HCA’s focus on booming markets where the population is growing, unemployment is low and thus, the demand for healthcare is rising—places like Houston, Nashville, Florida, and Ashville, N.C., where it recently struck a deal to acquire market leader Mission Health—have helped it grow admissions from paying customers even as other hospitals suffer from softer volumes. Its net revenue per adjusted admission has averaged between 2.5% and 2.7% over the past several years, driven by the local markets’ growing population and aging seniors’ demand for services, said CEO R. Milton Johnson, who is retiring at the end of this year to be succeeded by HCA President and Chief Operating Officer Sam Hazen.
When expanding into new territories, HCA eyes areas where it will dominate in terms of market share, which it can leverage into negotiating power to secure better rates from insurers.
“They want to be the No. 1 or No. 2 player in every market they go into,” said Brian Tanquilut, a Nashville-based equity analyst at investment firm Jefferies & Co. “They are very methodical, and they stick to a strategic playbook.”
That approach also means HCA generally steers clear of communities with less-than-favorable payer mixes.
“They tend not to open hospitals in impoverished neighborhoods and in states that pay poorly,” said Scott Phillips, managing director for Healthcare Management Partners.
Before 2017, HCA hadn’t entered a new market since 2003. In the years prior it invested in facilities, doctors and capabilities in areas where it already operated, taking share from its competitors. In Nashville, for instance, HCA expanded its pediatric services and is siphoning customers away from the renowned Monroe Carell Jr. Children’s Hospital at Vanderbilt, which has the higher prices typical of academic systems, Tanquilut said.
Under the direction of Johnson and Hazen, HCA has aggressively added outpatient clinics, urgent-care centers, free-standing emergency departments and ambulatory surgery centers to complement its hospitals. The company ended 2017 with 72 free-standing EDs and 123 urgent-care centers with plans to add more. Hazen said the company now has roughly 2,000 facilities providing outpatient care, which makes up 38% of HCA’s revenue.
“They were buyers of outpatient businesses and imaging clinics at the right time of the cycle, and now with the inpatient hospital being out of favor, they’ve been able to take advantage of the market,” said Nephron Research analyst Joshua Raskin.
He noted that HCA also empowers its hospital leaders with the tools necessary to drive change in their markets, such as the technologies needed to understand what staffing levels are necessary and what patient volumes will look like.
Those investments were possible because HCA generates a lot cash. Through its internal revenue-cycle management business, a service it also sells to other hospitals, HCA is adept at collecting payment from patients for services and making sure health plans pay up, Tanquilut said. In 2018, HCA will have generated $2.4 billion in free cash flows after investments, while other hospitals are pulling back on investments to pay off debt.
“They are operationally savvy,” said Paul Keckley, an industry analyst in Nashville. HCA leadership understands where to build its hospitals, how many beds to allot, how to staff and how to buy supplies. And their financial, operational and clinical decisions have been backed by hard data that HCA collected before it was necessary for compliance standards, Keckley said.
Importantly, HCA’s executives and managers are trained to demand and use that information, and are held accountable for producing results, said Dr. Mike Schatzlein, former CEO of Ascension Health’s St. Thomas Health who has also worked for HCA-owned hospitals. “Their operators know their numbers, and so they can react in real time and operate efficiently,” he said. “If you operate efficiently, that means you have reduced variation, waste and rework—and that results in higher quality.”
Analytics also gives HCA an edge in setting prices.
“They are the absolute leaders in maintaining discipline with their cost structure, but they also have world-class analytics to know where and when they can successfully raise prices, down to the smallest unit,” Paul Hughes-Cromwick, co-director of sustainable health spending strategies for consultancy Altarum, said in an email.
HCA’s aggressive pricing, enabled by its market share and patient volume, is a major factor in its financial success. Researchers have found that HCA’s negotiating power with insurers allows it to set high prices for its healthcare services. The high cost of healthcare in the U.S. is in part attributed to high prices, not the actual cost of services, experts say.
“They’re out to maximize profit, and one of the ways you can do it is by raising prices,” said Gerard Anderson, a health policy professor at Johns Hopkins University who has studied HCA’s prices.
Anderson and Johns Hopkins associate professor Ge Bai’s 2015 Health Affairs study found that HCA owned more than one-quarter of the top 50 U.S. hospitals with the highest ratio of charges to Medicare-allowable costs in 2012. Those 50 hospitals marked up charges by 1,000% on average. For-profit competitor Community Health Systems owned more than half of the hospitals. While charges don’t reflect the payment rates that most patients pay, uninsured patients often do end up paying full charges, Anderson said. About 28 million people were uninsured in 2016.
In another Health Affairs study published this month, Anderson and Bai found that the 20 hospitals in Florida with the highest prices for auto, workers compensation, liability and travel insurers in 2016 were all owned by HCA. Oftentimes, these nontraditional insurers pay for consumers’ medical expenses when an accident occurs, for example. But such insurers are smaller than giant HMO and PPO payers, and so have less negotiating power with big health systems.
The 20 HCA hospitals with the highest prices set them at 7.8 to 14.1 times the rate of Medicare, with a median price twice that of the other 124 hospitals operating in Florida that year, researchers found. Those 20 HCA hospitals received about a quarter of their commercial net revenue from such insurers—twice that of other payers—despite treating a small number of patients covered by them. The stakes are high for patients, because policies such as an auto insurance plan often have low coverage limits and high out-of-pocket spending.
HCA’s prices for HMOs and PPOs were largely in line with the other hospitals in Florida, the researchers said. The 20 highest-priced hospitals set prices at 1.7 to 4.1 times Medicare rates.
An analysis using the Modern Healthcare Metrics database, which relies on Medicare cost reports, found that HCA hospitals were docked $38.3 million in readmissions penalties and $9.1 million in value-based purchasing penalties in 2017.

A learning system

“It didn’t take one hospital 64 years to get these data. It took 43 hospitals 18 months.”
Dr. Jonathan Perlin
Chief medical officer
HCA Healthcare“It didn’t take one hospital 64 years to get these data. It took 43 hospitals 18 months.”
Dr. Jonathan Perlin
Chief medical officer
HCA Healthcare
HCA has leveraged its scale to solve big problems in clinical care and produce better outcomes for patients. The health system stores information from its 32 million patient visits per year in a clinical data warehouse and has a dedicated team of 300 professionals who find ways to use that data to improve best practices, said Dr. Jonathan Perlin, HCA’s chief medical officer. Some of HCA’s research into best practices have led to changes in clinical processes across the nation, he said.
In one case, HCA studied the difference in the rate of newborns going to the neonatal intensive-care unit after an early elective delivery. Over decades, the term of a mother’s pregnancy had been shortened from the normal 39 weeks because of convenience, but it wasn’t known if shorter terms meant higher risk of newborn complications.
Because so many babies are delivered at HCA hospitals, the health system was in a position to find out. It studied 18,000 births over 90 days and found that the risk for complications requiring a baby to go to the NICU was four times greater when delivered electively at 37 weeks and more than two times greater at 38 weeks than delivering at full term.
Similarly, HCA used its patient data to test the best approaches to preventing MRSA and other hospital-acquired infections over 18 months. The chain managed to reduce MRSA rates by 37% and cut all potentially life-threatening blood stream infections in the ICU by 44%. The study changed practice in the U.S. and worldwide, Perlin said.
“This is really what a learning health system can allow, which was research conducted during the course of normal operations by normal care providers at speed and at scale to definitively answer a question that’s important for the patients we’re privileged to treat,” Perlin said. “It didn’t take one hospital 64 years to get these data. It took 43 hospitals 18 months.”
HCA’s track record isn’t spotless. Its ill-fated 1994 merger with Louisville, Ky.-based Columbia Hospital Corp. ended with one of the largest Medicare fraud settlements when Rick Scott, who is now the governor of Florida and running for the U.S. Senate, was at the helm of the merged company. The investigation and a roughly $2 billion settlement were an embarrassment to HCA’s culture and tarnished its reputation at the time. It is largely now considered a distant memory by many in the industry.
The hospital system has also been criticized for refusing to treat patients who came to the emergency department with nonurgent conditions unless they paid upfront, a strategy that helped reduce ED costs and overcrowding. A 2012 New York Times story also accused several HCA Florida hospitals of performing unnecessary cardiac procedures to grow profits.
Critics might take issue with HCA’s for-profit model, Keckley said. HCA doesn’t take many risks, and it doesn’t chase trends. It makes decisions about clinical programs based on potential payoff, and will leave a market if it’s not profitable enough, Keckley said.
“They don’t want to be on the bleeding edge of anything,” he said. But “it’s an interesting model and you have to respect their success. It’s their efficiency and their data-driven approach to looking at opportunity that I think is exceptional bar none.”

Moody’s picks 5 early winners in biosimilar market


  • While biosimilars have yet to take off in the U.S., top credit rating agency Moody’s remains optimistic of the future market opportunity for the biologic copycats, calling the competition “a rising headwind for branded pharmaceutical companies” in an Oct. 4 report.
  • The agency’s analysis highlighted five pharmaceutical giants that stand to gain the most from biosimilars, as well as four companies at the highest risk from these drugs.
  • In Europe, annual sales erosion is expected at eat between 25% and 30% out of branded sales, Moody’s found, while the U.S. remains “slow to date” in adoption.

Eight of the top 10 selling drugs in the world were biologics in 2017, creating a huge market opportunity for biosimilars. Moody’s analysts are paying attention to how the still-developing area could affect the bottom lines of the industry’s biggest players.
“Over the next year or so, as biosimilars gain traction globally, several branded pharmaceutical companies will face declining sales of important blockbuster drugs,” Michael Levesque, a Moody’s senior vice president and lead author of the report, said in an Oct. 4 statement.
“Biosimilars have seen strong uptake in Europe and this trend will accelerate as the biosimilar market there continues to develop, with more drugs approved and launched.”

The winners

The report selected Pfizer, Biogen, Novartis, Amgen and Mylan as the initial leading biosimilar companies by sales, with a slate of already launched biosimilars and others in development between them.
Moody’s expects Pfizer to post $700 million in biosimilar revenues for 2018, growing to $1.5 billion in 2020.
Biogen, through its share of a joint venture with Samsung Bioepis, is poised to be runner-up to Pfizer, with $550 million in expected 2018 sales from biosimilars and $1 billion by 2020.
For 2020, Moody’s estimated Novartis’ Sandoz unit to log $750 million in biosimilar revenue, and Amgen and Mylan to reach $500 million each.

Companies most at risk from biosimilars

The report also concluded Roche, Amgen, AbbVie and Johnson & Johnson will likely face declining sales in the next 12 to 18 months for key products dinged by biosimilar competition.
Nearly half of Roche’s global sales come from three cancer biologics: Rituxan (rituximab), Herceptin (trastuzumab) and Avastin (bevacizumab). The first two are now facing European biosimilars and Moody’s deemed it likely they will also see U.S. copycats by 2019.
Other at-risk drugs include Amgen’s Neulasta (pegfilgrastim) and Epogen (epoetin alfa) — which combine to make up about 25% of total sales for the company —​ AbbVie’s Humira (adalimumab) and J&J’s Remicade (infliximab).

Shifting regulatory landscape

Amgen is in a unique position, standing both to gain and to lose from biosimilar uptake. Copycat competition could take a bite out of Amgen’s biologic sales, even as the California biotech seeks to do the same to some of its large-cap peers.
This fits with a notable distinction between the markets for biosimilars and generics: large pharma has been on both sides of the biosimilar game, as Richard Mortimer, a managing principal at the Analysis Group who specializes in health economics, recently noted in an Oct. 4 talk on the subject.
With generics, the pharma industry largely stood united against companies that focused exclusively on knockoff copies. Biosimilars, however, have so far led to some splits in the ranks, as the high-profile legal battles between Novartis and Amgen, and Pfizer and J&J have shown.
Mortimer predicted drugmakers will be more active in promoting biosimilars than generics. He also expects to see more brand-brand competition between biologics and their copycats, partially due to the absence — so far — of any fully interchangeable biosimilars in the U.S.
Moody’s found the U.S. regulatory framework to still be evolving, but was optimistic that biosimilars will be helped by future efforts from the Food and Drug Administration and from the White House’s drug pricing blueprint.

Retrophin to Present Long-Term Phase 2 Sparsentan Data at Kidney Meeting


Retrophin, Inc. (NASDAQ: RTRX) today announced that it will present new data examining the long-term effects of sparsentan in focal segmental glomerulosclerosis (FSGS), at the American Society of Nephrology (ASN) Kidney Week 2018. The Company will present an 84-week analysis of the open-label extension portion of the Phase 2 DUET Study, as well as preclinical findings demonstrating that treatment with sparsentan provides nephroprotection in an autosomal mouse model of Alport syndrome. FSGS and Alport Syndrome are rare, progressive kidney disorders that often lead to end-stage renal disease (ESRD). ASN Kidney Week 2018 is being held October 23–28, 2018, in San Diego, CA.
Oral Presentation:
Long-term Effects of Sparsentan, a Dual Angiotensin and Endothelin Receptor Antagonist in Primary Focal Segmental Glomerulosclerosis (FSGS): Interim 84-Week Analysis of the DUET Trial
Abstract Program #: FR-OR087 
Session: Glomerular Diseases: Clinical, Outcomes, and Trials
Location: Room 24A, San Diego Convention Center
Date & Time: Friday, October 26, 2018, 6:18 p.m. – 6:30 p.m. PT
Poster Presentation:
Sparsentan, a Dual Angiotensin II Type 1 (AT1) and Endothelin Type A (ETA) Receptor Antagonist, Prevents Renal Disease in COL4A3 -/- Autosomal Alport Mice
Poster #: FR-PO624
Session: Genetic Diseases of the Kidney Non-Cystic II
Location: Exhibit Hall C, San Diego Convention Center
Date & Time: Friday, October 26, 2018, 10:00 a.m. – 12:00 p.m. PT