New York City is a hot spot for illegal Medicaid enrollment

New York state is grappling with a Medicaid shortfall in the billions of dollars. And one of the main reasons is improper enrollment.

Using annual information from the Census Bureau to assess the demographic make-up of Medicaid enrollees over time, researcher Aaron Yelowitz and I estimated that 2.3 million to 3.3 million Medicaid enrollees nationally make an income in excess of what is allowed.

This is of increasing importance given that ObamaCare massively expanded what was historically a welfare program for vulnerable populations like the disabled and low-income children and pregnant women — and tens of billions of taxpayer dollars are at stake.

Excluding traditional pathways onto Medicaid (such as through disability or pregnancy), Yelowitz and I concluded that the number of working-age New York state residents on Medicaid who have incomes above the eligibility threshold rose by more than 80 percent between 2012 and 2017. We estimated that between 337,000 and 433,000 working-age New York state residents with income above the allowed limit are improperly enrolled in Medicaid.

And nearly half of this improper enrollment is in New York City, with 30 percent in The Bronx and Queens, where a few neighborhoods have among the highest percentage of improper enrollees of anywhere in the country.

In The Bronx, particularly the Concourse, Highbridge and Mount Eden regions, we found that roughly 40 percent of all working-age adults with incomes exceeding income eligibility thresholds were enrolled in Medicaid in 2017. The next-worst area is in Queens — the Elmhurst/South Corona, Jackson Heights/North Corona and Sunnyside/Woodside regions. In those areas, there are likely tens of thousands of ineligible Medicaid enrollees.

ObamaCare deserves much of the blame for the surge in improper enrollment. It created a new category of Medicaid recipients — lower-income, able-bodied, working-age adults — with the federal government paying a much larger share of their expenses than for traditional enrollees.

From 2013 — the year before ObamaCare’s Medicaid expansion took effect — to 2018, there has been a surge of Medicaid payments out of compliance with legal criteria. In fact, improper Medicaid payments more than tripled.

While states bear some of the burden for improper spending, most of the bill is picked up by the federal government. We estimated that improper payments now exceed 20 percent of federal Medicaid expenditures, an amount above $75 billion each year.

As a result of ObamaCare’s more generous Medicaid funding, many states — including New York — have stopped properly assessing whether applicants are eligible before they enroll.

While the health-care industry, particularly insurance companies, has benefitted from ObamaCare’s windfall of federal cash and improper Medicaid enrollment, traditional enrollees face a harder time obtaining care — and taxpayers are stuck with an enormous tab.

‘We estimated that improper payments now exceed 20 percent of federal Medicaid expenditures, an amount above $75 billion each year’

The inspector general at the federal Department of Health and Human Services found substantial problems with New York state’s process for reviewing Medicaid eligibility. The state made large numbers of errors and did not always maintain documentation. An audit of the entire state’s program found 15 percent of applicants improperly enrolled. The size of the error was staggering, with the inspector general estimating that New York state improperly claimed more than $1.8 billion in a six-month period on behalf of more than 900,000 ineligible enrollees or people who were enrolled without having submitted all the proper documentation.

In order to get a handle on its budget crisis, New York should conduct targeted eligibility reviews in The Bronx and Queens. If the state doesn’t act, the federal government must step in and require eligibility reviews in these hot spots and others around the country. Some level of government owes it to taxpayers and to those who are truly eligible to get enrollment right.

Brian Blase, a special assistant to President Trump at the National Economic Council from 2017-19, is president of Blase Policy Strategies. Aaron Yelowitz is an economics professor at the University of Kentucky and a senior fellow at the Cato Institute. They are co-authors of the new Mercatus Center study, “The ACA’s Medicaid Expansion: A Review of Ineligible Enrollees and Improper Payments.”

https://nypost.com/2019/11/30/new-york-city-leads-the-country-in-illegal-medicaid-enrollment/

People on Medicare due to disability make up most opioid-linked deaths

New findings from The University of Texas Medical Branch at Galveston show that patients qualifying for Medicare because of a disability have the highest rates of opioid overdose deaths compared with older Medicare beneficiaries and commercial insurance beneficiaries. The findings are now available in JAMA Network Open. The study, led by Yong-Fang Kuo, UTMB professor in the department of preventive medicine and population health, found that Medicare beneficiaries who qualify because of a disability are a growing group of patients hospitalized for opioid or heroin overdose and account for 25 percent of deaths from prescription opioid overdose each year. Previous research shows that not many of these patients make use of opioid treatment programs.

In the study, the researchers analyzed a nationally representative sample of Medicare data, including 1,766,790 people who qualified for Medicare because of a disability to assess the rate of opioid overdose deaths and identify its associated risk factors. Although these disability patients account for only 14.9 percent of the entire Medicare population, they were also found to represent 81 percent of all opioid-related deaths among this group.

“We found that among the patients who have Medicare because of disability, the rates of opioid overdose deaths were higher among people who grapple with substance misuse, psychiatric diseases or chronic pain,” said senior author Kuo of UTMB.

“Right now, there’s a large federal push to increase access to opioid misuse treatment programs and these efforts work more effectively with accurate targeting of high-risk populations. Our findings suggest that Medicare data can help to identify people who can really benefit from these programs.”

###

Other authors include UTMB’s Mukaila Raji and James Goodwin.

https://www.eurekalert.org/pub_releases/2019-11/uotm-pwq112619.php

How gene-edited white blood cells are helping fight cancer

For the first time in the United States, a gene editing tool has been used to treat advanced cancer in three patients and showed promising early results in a pilot phase 1 clinical trial. So far the treatment appears safe, and more results are expected soon.

To develop a safer and more effective treatment for cancer patients, scientists from the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy in San Francisco and Tmunity Therapeutics, a biotech company in Philadelphia, developed an advanced version of immunotherapy. In this treatment, a patient’s own immune cells are removed from the body, trained to recognize specific cancer cells and then finally injected back into the patient where they multiply and destroy them.

Unlike chemotherapy or radiation therapy, which directly kills cancer cells, immunotherapy activates the body’s own immune system to do the work. This team used a gene editing tool called CRISPR to alter immune cells, turning them into trained soldiers to locate and kill cancer cells. By using this technique, the team hoped to develop a more effective form of immunotherapy with minimal side effects.

I am trained as a pharmaceutical scientist and a biomolecular engineer, and I was particularly interested to learn about this new therapy because my lab focuses on editing the gene editors. In particular, I am trying to develop even better CRISPR-based gene editors for the diagnosis and treatment of cancer and other disorders. We combine chemistry, biology and nanotechnology to engineer, control and deliver gene editing tools more efficiently and precisely.

A pseudo-colored scanning electron micrograph shows two T-cells (red) attacking a cancer cell (white). Researchers are creating more powerful cancer treatments by editing the genes inside the T-cells. Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health, CC BY-NC

Training the immune cells to find and kill cancer

The first step in making these tumor-killing cells used in the cancer drug trial was to isolate the T-cells – a type of white blood cells that fights pathogens and cancer cells – from the blood of the cancer patients. Two patients with advanced multiple myeloma and one patient with myxoid/round cell liposarcoma were enrolled for this study.

To arm the T-cells and bolster their tumor-fighting skills without harming normal cells, scientists genetically engineered the T-cells – disabling three genes and adding one gene – before returning them to the patients.

The first two of these deleted genes encode T-cell receptors, which are proteins found on the surface of the T-cells that can recognize and bind specific molecules, known as antigens, on cancer cells. When these engineered T-cells bind to these antigens, it allows them to attack and directly kill the cancer cells. But the problem is that a single T-cell can recognize multiple different antigens in the body, making them less focused on finding the cancer cells. By eliminating these two genes, the T-cells are less likely to attack the wrong target or the host, a phenomenon called autoimmunity,

In addition, they disrupted a third gene, called programmed cell death protein 1, which slows down the immune response. Disabling the programmed cell death protein 1 gene improves the efficiency of T-cells.

The final step in the transformation of these cells was adding a gene which produces a new T-cell receptor that recognizes and grabs onto a specific marker on the cancer cells called NY-ESO-1. With three genes deleted and one added, the T-cells are now ready to fight cancer.

Where is CRISPR in this clinical trial?

So how exactly did this team edit a T-cell? They utilized CRISPR/Cas9 gene editing technology that uses two components: a guide CRISPR molecule that finds and binds the target gene site; and a molecular scissor, Cas9, that snips the DNA, ultimately disabling the gene.

The team used electroporation, a technology that creates temporary holes in the cell membrane, to deliver the Cas9 protein along with the guide molecules that targeted the three genes of interest in millions of T-cells.

After disrupting the three genes with CRISPR, the team used a safe, deactivated virus to deliver a gene to the T-cell that would enable it to recognize the cancer-specific marker – NY-ESO-1. Removing these genes from millions of cells and then allowing the T-cells to multiply into billions of cells outside the body in petri dishes can take several days to weeks.

Four days before injecting the CRISPR-modified T-cells, the team gave each of the three patients several doses of chemotherapy drugs to deplete the existing white blood cells in their bodies.

Finally, approximately 100 million modified T-cells per kilogram of body weight were injected into the patients as a single infusion.

After modifying the T-cells by clipping out three genes with CRISPR and adding a new one, the immune cell becomes better at locating and killing cancer cells. Piyush Jain, CC BY-SA

Promising future of CRISPR

The team monitored the patients continuously for the first 28 days after injecting the T-cells. Then they followed up monthly for six months; after that every three months by monitoring any adverse events such as immune reaction. The T-cell therapy is frequently associated with various side effects such as fever, muscle pain, headaches, confusion, seizures, low blood pressure, bleeding disorders and multiple organ dysfunction. The team noted no signs of toxicity in any patient, which is exciting.

But the first patient with advanced multiple myeloma had continued growth of a tumor after 60 days. While the treatment seemed not so successful for the first patient, the phase 1 clinical trial is mainly designed to test the safety, and the team reported no toxicity to any patient.

The second patient with advanced myxoid/round cell liposarcoma was monitored using serial CT scans and seemed stable after 90 days. The third patient with multiple myeloma started the trial recently and is too early for any results. The fact that there were no serious toxicity issues with this new therapy involving the CRISPR-based gene editing technology in cancer patients is a remarkable step toward the broad use in the clinic.

https://theconversation.com/how-gene-edited-white-blood-cells-are-helping-fight-cancer-126806

‘Cultured’ meat could create more problems than it solves

Cultured or in vitro meat, also called “clean meat” by its supporters, is meat produced in a laboratory using bioengineering techniques.

In 2013, Mark Post, professor at Maastricht University, presented the first hamburger made of cultured meat. Since then, the dream of being able to create and consume meat based on “cellular agriculture”, without livestock farming, has gained support among both animal-rights activists and, especially, players in the industry. A large number of start-ups have been created, with many sponsored by big names in the food industry. The ambition is to market cultured beef, poultry or fish meat at an affordable price by 2020 or 2022.

With this goal in mind, in 2018 the US Food And Drug Administration established a regulatory framework and this has opened the way for the marketing of these products.

So, is artificial meat a true food revolution or an impossible utopia?

What will the global diet be in 2050?

According to the United Nations Food and Agriculture Organisation (FAO), conventional meat production accounts for a significant share of greenhouse gas emissions (18%) and land use (30%), as well as global consumption of water (8%) and energy. The FAO also estimates that meat consumption will double by 2050, while meat production is already close to its peak. What’s the solution to this problem?

According to Mark Post, “cows are very inefficient”, with a “bioconversion rate” estimated at 15%. In other words, to produce 15 grams of meat, you need 100 grams of vegetable protein. The only way to produce meat sustainably is to increase the efficiency rate.

Different methods have been considered in the past, such as producing meat made of plant- or insect-derived proteins. These alternatives, however, don’t always satisfy consumers due to cultural preconceptions and the difficulty of mimicking the taste and texture of conventional meat. In vitro meat could help bypass these problems.

How is meat grown?

In concrete terms, the first step is to isolate a small number of satellite muscle cells from an adult animal. The physiological function of those satellite cells is to participate in muscle regeneration: they are not yet muscle cells, but stem cells that are able to multiply and, under the influence of certain hormones, to differentiate into muscle cells.

The satellite cells are grown in bioreactors, which are sterile enclosures containing nutrient liquids, under stimulation with growth factors to induce rapid proliferation. They are then transformed into muscle cells and mechanically assembled into muscle tissue and then a consumable artificial steak…

According to the website of Mosa Meat, the Dutch company founded by Mark Post, the production of cultured meat would significantly reduce the environmental impact of meat production as well as the risk of infectious diseases transmitted from animals to humans. Moreover, the company asserts that the taste of cultured meat is close to that of conventional meat.

Cellular agriculture has also been touted by Paul Shapiro, author of the bestseller Clean Meat: How Growing Meat Without Animals Will Revolutionize Dinner and the World and CEO of the Better Meat Company. He asserts that cultured meat is the key to feeding a world population that will reach around 9.5 billion by 2050, while respecting animals and preserving the environment.

Higher environmental costs than originally thought

As indicated by a 2011 study, cultured meat can offer many advantages over conventional meat: It would reduce greenhouse gas emissions by 78-96% and require 7-45% less energy and 82-96% less water. However, more recent research suggests that over the long term, the environmental impact of lab-grown meat could be higher than that of livestock. Unlike the previous research, these studies considered not only the nature of the gases emitted, but also the energy costs of the infrastructures required for cell culture.

Animals have an immune system that naturally protects them against bacterial and other infections. This is not the case for cell culture, and in a nutrient-rich environment, bacteria multiply much faster than animal cells. To avoid producing a steak made up of more bacteria than meat, it is essential to avoid contamination, and that requires a high level of sterility.

In the pharmaceutical industry, cell cultures are carried out in highly controlled and sanitized “clean rooms”. Sterility is most often guaranteed by using disposable plastic materials. This significantly reduces the risk of contamination, but generates plastic waste, whose level in ecosystems is already alarming. Some of the culture materials are made of stainless steel and can thus be steam sterilized or washed with detergents, but these treatments also have an environmental cost.

While few studies have been done on the environmental impact of the pharmaceutical industry, the available data suggest that its carbon footprint may be 55% higher than that of the automotive industry.

Importantly, we should not forget that livestock fulfils many functions other than just the production of meat. It contributes to the recycling of large quantities of plant waste that cannot be consumed by humans and produces fertilizer. Furthermore, pastures capture and store carbon. What will replace them if meat is produced by cell culture? This means that it is extremely complex to evaluate the long-term environmental cost of a transition from conventional to cultured meat.

Anabolic hormones and endocrine disruptors: significant risks

In animals, muscle volume increases slowly, and it takes time for muscular satellite cells to multiply. To obtain what an animal produces over several years in just a few weeks in vitro, it is necessary to continuously stimulate proliferation of the satellite cells with growth factors, including anabolic sex hormones.

These hormones are present in animals and humans, as well as in conventional meat. They stimulate protein synthesis in cells, resulting in increased muscle mass. They can therefore be rightly described by industry as “natural growth factors”. However, overexposure to them has established deleterious effects. In Europe, the use of growth hormones in agriculture has been prohibited since 1981 by directive 81/602. This ban was confirmed in 2003 by directive 2003/74 and validated by the European Food Safety Authority (EFSA) in 2007. What will the final concentration of these hormones be in cultured meat?

In addition, a growing number of studies have documented the toxicity of commonly used plastic products. Endocrine disruptors, compounds that can interfere with the hormone system and disrupt it, can be transferred from plastic packaging to food. Unsurprisingly, the same phenomenon has been documented in cell cultures grown in plastic containers by in vitro fertilization.

Unless the use of plastic in the production of meat by cell culture is tightly controlled, the meat could be contaminated with endocrine disruptors and other substances before it is even packaged.

Healthy and sustainable nutrition also means education

Cultured meat is presented today as a high-tech product that has the potential to be both ecologically and morally responsible. But it can only become an alternative to traditional meat by conquering the world market—in other words, by being affordably priced for consumers and profitable for producers, and that requires high-volume, low-cost production techniques. Will the impacts on health and the environment still be taken into consideration with the transformation of the scale of production?

It’s also important to remember to that high consumption of meat is detrimental not only to the environment but also to human health. However, many consumers are not aware or decline to accept such conclusions.

To achieve a diet that is both sustainable and healthy, it is therefore essential to improve information and education to stimulate an informed debate on the crucial issue of meat consumption.

---

Explore further

Scientists enhance color and texture of cultured meat

https://medicalxpress.com/news/2019-11-cultured-meat-problems.html

Hardening of the arteries: Platelets, inflammation, rogue protein v. the heart

The Lipid Hypothesis of coronary artery disease has long held that a high level of cholesterol is the causative factor of atherosclerosis, but a group of New York scientists is making a powerful case for platelets as the trigger of an artery-damaging inflammatory response.

Heart disease, a term that refers to a vast number of complex conditions, is most frequently used to define coronary artery disease, or atherosclerosis. The condition is a leading cause of cardiovascular deaths in Western countries and is marked by arterial deposits of plaque, which is composed of cholesterol, fatty material, calcium deposits and a motley collection of biological debris.

Over time, plaque not only hardens, but causes afflicted arteries to narrow, limiting the free flow of oxygen-rich blood. The Lipid Hypothesis, which continues to hold sway, is also known as the Cholesterol Hypothesis. It isn’t, however, the entire story of how plaque forms and narrowed arteries set the stage for heart attack and stroke.

Scientists at New York University School of Medicine have been investigating the role of platelets in the evolution of atherosclerosis. Platelets are tiny, sticky cellular fragments whose key function is to aid the formation of blood clots. In injuries that cause bleeding, platelets are necessary to clot blood at the wound site.

But the NYU researchers are finding that platelets have functions beyond those involved with preventing severe bleeding. These sticky little fragments play a big role in inflammation and plaque.

Drs. Tessa Barrett and Jeffrey Berger of the Marc and Ruti Bell Program in Vascular Biology at NYU investigated platelets and platelet activation. They were particularly interested in how platelets promote inflammation and spur the development of macrophage-platelet aggregates. All are key actors in the development of plaque, the scientists say. While the Lipid Hypothesis provides a foundational understanding of atherosclerosis, it doesn’t provide an intricate understanding of a sometimes deadly drama that plays out in affected arteries.

Detailing their findings in Science Translational Medicine, Barrett and Berger, along with a team of NYU cardiovascular investigators, explained how a range of molecular processes can lead to the types of blockages that underlie coronary artery disease.

The scientists found, for example, that white blood cells are not innocent bystanders in the cascade of events that leads to atherogenesis, the formation of plaque in arteries. The team identified monocytes and macrophages as constituents with noteworthy roles.

A mini-lesson in cell biology is necessary at this juncture to better understand those cells. Monocytes are precursors to macrophages. Both are leukocytes—white blood cells—and both are also called myeloid cells.

“Activated platelets locally release a host of inflammatory mediators that support the chemotaxis, adhesion and transmigration of leukocytes to sites of inflammation,” wrote Barrett, lead author of the research. Chemotaxis refers to the movement of leukocytes into areas of the vessel with high inflammation.

Additionally, the NYU investigators also found that platelets have an influence on a protein known as SOCS3. And platelet regulation of myeloid SOCS3, the team discovered, accelerates the development of atherosclerosis.

Although platelets are crucial to the development of atherosclerosis, they are not necessarily part of thrombosis—forming clots in arteries, the team found. “Our findings define an atherogenic role of platelets and highlight how, in the absence of thrombosis, platelets contribute to inflammation,” Barrett reported.

“Atherosclerosis, a chronic vascular inflammatory disease, represents the interplay between lipid deposition in the artery wall and unresolved inflammation,” Barrett underscored. “Here, we reveal that platelets induce monocyte migration and recruitment into atherosclerotic plaques, resulting in plaque platelet-macrophage aggregates.”

Working with specially bred Ldlr mice that were fed a Western diet, the team found that “platelets drive atherogenesis by skewing plaque macrophages into an inflammatory phenotype.” This, in turn, influences SOCS3 expression, the team found.

Translating their data to humans with cardiovascular disease, the investigators discovered that among women who had heart attacks, there was an increase of the SOCS3 protein and a concomitant increase in monocyte-platelet aggregates.

A second group of patients with atherosclerosis in vessels in their legs also demonstrated evidence of elevated SOCS3 proteins, elevated platelet activity, and inflammation. Collectively, the data provided a causative link between platelet-mediated myeloid inflammation and dysfunction, SOCS3 and cardiovascular disease.

“Recruitment of monocytes to the sub-endothelium and their subsequent differentiation to macrophages are key steps in atherosclerotic plaque formation and progression. Macrophages, critical effectors of inflammation and innate immunity, are key pathogenic drivers of vascular disease,” Barrett wrote.

---

Explore further

Blocking a hormone’s action in immune cells may reduce heart disease risk

---

More information: Tessa J. Barret et al. Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis, Science Translational Medicine (2019). DOI: 10.1126/scitranslmed.aax0481

https://medicalxpress.com/news/2019-11-hardening-arteries-platelets-inflammation-rogue.html

Y-mAbs Starts Rolling Submission to FDA for Naxitamab Neuroblastoma Treatment

Y-mAbs Therapeutics, Inc. (the “Company” or “Y-mAbs”) (Nasdaq: YMAB), a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today announced that it has submitted to the U.S. Food and Drug Administration (“FDA”) the first portions of its Biologics License Application (“BLA”) for naxitamab for the treatment of patients with relapsed/refractory high-risk neuroblastoma under the FDA’s Rolling Review process.

In August 2018, naxitamab, which is an anti-GD2 monoclonal antibody, received Breakthrough Therapy Designation by the FDA, which facilitates frequent interactions with the FDA review team. The Rolling Review process allows Y-mAbs to submit individual portions of the BLA for review, rather than waiting until all portions are completed and submitted to the FDA for review. Upon potential approval, the Company intends to commercialize naxitamab in the U.S.

https://www.streetinsider.com/Corporate+News/Y-mAbs+Therapeutics+%28YMAB%29+Initiates+Rolling+Submission+of+BLA+to+U.S.+FDA+for+Naxitamab+for+Treatment+of+Neuroblastoma/16193623.html

Removal of Generic Litigation Overhang Could Push Amarin to $25-30 – Jefferies

Jefferies analyst Michael Yee provided his takeaways from a recent call with a patent lawyer related to ongoing generics litigation for Amarin’s (NASDAQ: AMRN) Vascepa. AMDA litigation between Amarin and generic filers Reddy’s and Hikma has come into focus amid the approval of the sNDA for Vascepa and a trial is set to start on 1/13/20.

Yee said they came away from the expert call positive as many generic claims have already abandoned or invalidated by the court and, in the opinion of the patent attorney, a settlement or outright win by Amarin is probable.

The analyst said a settlement would be a positive outcome and could potentially push the stock to $25-30 as a key overhang is removed.

“We still think a settlement would be a great outcome as it would benefit all parties involved, including removing an overhang on AMRN and the generics potentially getting ~6 months of limited exclusivity in a $5B+ mkt later in 2029, which is worth a lot to generic companies,” Yee commented. “We estimate that every six mos of generic entry earlier than 2029 equates to $2/share, though Teva has already settled for 2029.”

If a settlement is not reached, the expert still thinks Amarin would likely win the case outright.

“Our DCF suggests the stock is worth $30 on peak sales of $3-4B, and every $1B higher peak flows to the bottom line and is worth $5/sh upside,” Yee commented.

In addition to the takeaways on the generics litigation, Yee previewed upcoming competitor data. While data from competitor fish oils over the next 12 months could result in some headline noise, the big picture shouldn’t affect Amarin, he said.

The analyst reiterated a Buy rating and $30.00 price target on AMRN.

https://www.streetinsider.com/Analyst+Comments/Removal+of+Generic+Litigation+Overhang+Could+Push+Amarin+%28AMRN%29+to+%2425-30+-+Jefferies/16193578.html

Biotech VC Down 20% in US as Policies Drive Away Foreign Investors, BIO

Reforms to a US national security regulation are putting off foreign investors and driving down VC investment in the biotech space by as much as 20 percent, says BIO’s David Thomas.

In August 2018, Congress passed the Foreign Investment Risk Review Modernization Act (FIRRMA) as part of the Fiscal 2019 National Defense Authorization Act. The Act broadened the scope and oversight of the Committee on Foreign Investment in the United States (CFIUS) to include the review of foreign investments in companies involved in critical technology, all in the name of national security.

Whether the ruling was intended to specifically curb investment from China, as many commentators at the time suggested, it has had an adverse impact on venture capital (VC) investment in biotech, according to the Biotechnology Innovation Organization (BIO).

David Thomas, vice president of Industry Research at the advocacy group, told us, that Congress “expanded the regulation to include biotechnology as one of these core areas that needs to be governed for national security purposes,” and additional procedures have made foreign investors look to other markets.”

US companies with foreign investment now have to go through an application and review process which can take months and involve substantial legal fees, Thomas told Xconomy journalist Mike Ward at the recent BIO-Europe event in Hamburg, Germany. “It’s starting to slow things down, and we’ve seen a couple of investments not go through because one of the key components of a deal was this outside, foreign investment.”

BIO uses multiple databases to track the biotech market, and while official figures for 2019 will not be available until the beginning of next year, preliminary numbers show investment in VC is down around 20 percent on the year prior.

“We actually see it going up in Europe where we don’t have that policy,” Thomas continued, adding a further expansion in CFIUS’ remit is only going to push investors further away from US biotech companies.

“They expanded the review to incorporate companies working on genetic data of patients. If you have genetic data stored on your server, you would also potentially [fall] under the rules and regulations, so that is pretty much everyone working in cancer and rare disease where you need some type of genotyping,” he added.

This latest expansion of CFIUS is only in a pilot stage, and Thomas said continued advocacy could help reverse the VC spending trend. “The government is trying to find out where to draw the line and BIO’s role is to have conversations with the Treasury to identify how broad this is and maybe where that scope could be narrowed.”

Drug Pricing Proposals

Thomas also spoke about the impact of proposed pricing controls in the US, specifically plans to reference drug prices in the US to those in Europe and Japan. The result, he said, is that the biotech index is down 13 percent over the past four and a half years, when conversations about drug pricing really began. “Things have gone up and down but really never recovered back to those 2015-2016 highs,” Thomas added.

The most extreme plan is the Democrats’ HR3 Bill, put forth by Speaker Nancy Pelosi. The Congressional Budget Office (CBO) said in October that the Bill could lead to a reduction in revenues of $0.5 trillion to $1 trillion over the next 10 years and “would lead to a reduction of eight to 15 new drugs coming to market.”

BIO’s own analysis, done in conjunction with the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Council of State Bioscience Associations (CSBA), has placed the figure at around 56 fewer new medicines for patients over the next 10 years, but Thomas told us the actual figure could be even higher in the longer-term. “Some of the companies that are just starting off right now with great innovations are going to take ten to twenty years. There is going to be less capital going into those companies, and so it could be another zero on the end of that if you look at the longer timeframe. It would be devastating to innovation.”

And with most pharma firms fixing their R&D budgets as a percentage of their revenues – roughly 15 to 20 percent – controlled drug prices would mean less R&D, less innovation, and less money for partnering activities, he added. “There might be less beneficial deal terms here [at BIO-Europe] or less deals overall, which impacts everyone here at this event.”

https://xconomy.com/national/2019/11/29/biotech-vc-down-20-in-us-as-policies-drive-away-foreign-investors-bio/

Biotech Investors: Mark Your Calendar For These December PDUFA Dates

Biotech stocks had a fairly robust November, with the iShares NASDAQ Biotechnology Index IBB 0.22% advancing over 10% for the month. This compares to the 3% gains for the S&P 500 Index.

The month witnessed eight new molecular entity, or NME, approvals, taking the total NME approvals for the year to 41 compared to 55 approvals by the same time last year.

The FDA approved two drugs for sickle cell disease this month: Novartis AG’s NVS 0.29% Adakveo as well as Global Blood Therapeutics Inc’s GBT 0.36% Oxbryta.

PDUFA dates are deadlines for the FDA to review new drugs. The FDA is normally given 10 months to review new drugs. If a drug is selected for priority review, the FDA is allotted six months to review the drug. These time frames begin on the date that an NDA is accepted by the FDA as complete.

As we approach the end of the year, here’s a look at a few drugs that await FDA’s final word in December.

Will Roche’s Tecentriq Win FDA Backing For Lung Cancer?

• Company: Roche Holdings AG Basel ADR RHHBY 0.05%
• Type of Application: sBLA
• Candidate: Tecentriq and Bristol-Myers Squibb Co’s BMY 1.16% chemo medications Carboplatin and Abraxane
• Indication: non-squamous non-small cell lung cancer, or NSCLC
• Date: Dec. 2

Roche’s Tecentriq along with chemo combination is being evaluated as a first-line treatment for patients with metastatic non-squamous NSCLC, who do not have EGFR or ALK genomic tumor aberrations.

Following the acceptance of the sBLA with priority review designation in January, the FDA had initially set a PDUFA action date of Sept. 2 which was subsequently extended by three months.

Amgen’s Biosimilar For J&J’s Inflammation Drug Remicade Awaits FDA Nod

• Company: Amgen, Inc. AMGN 0.08%
• Type of Application: BLA
• Candidate: ABP 710 or Infliximab biosimilar
• Indication: migraine in adults
• Date: Dec. 14 (Biosimilar User Fee Act date)

ABP 710 is a biosimilar candidate to Johnson & Johnson’s JNJ 0.17% Remicade, which has been approved for multiple indications such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ankylosing spondylitis.

Amgen had submitted the BLA in December 2018. Incidentally, the company withdrew its European filing for ABP 710 in May, citing a change in product strategy for the pipeline candidate.

D-Day Set For Avadel’s AV001 After 3-Month Extension

• Company: Avadel Pharmaceuticals PLC AVDL 2.25%
• Type of Application: NDA
• Candidate: AV001
• Indication: Sterile injectable product for the hospital market
• Date: Dec. 15

The NDA was originally accepted for review in May under Priority Review program, with the decision date fixed for Sept. 15. The FDA extended the review period by three months, requiring time to review submissions related to additional analytical information sought for by the agency. The company maintained its commercial launch schedule intact at the first quarter of 2020.

AV001 is marketed as an unapproved marketed product by another company, and Avadel’s development and formulation has improved its safety profile, the company said.

Bausch Health’s Acne Treatment

• Company: Bausch Health Companies Inc BHC 0.32%
• Type of Application: NDA
• Candidate: IDP-123 (tazarotene 0.045%) lotion
• Indication: Acne treatment
• Date: Dec. 22

The FDA accepted the NDA filed by Bausch Health’s Ortho Dermatologics subsidiary in August. If approved, IDP-123 is expected to be the first tazarotene treatment available in lotion form.

Can Correvio’s Abnormal Heart Rhythm Drug Clear FDA Hurdle?

• Company: Correvio Pharma Corp CORV 2.36%‘s
• Type of Application: NDA
• Candidate: Brinavess
• Indication: recent onset atrial fibrillation
• Date: Dec. 24

The FDA has refused to file the initially submitted NDA in August 2017, citing insufficiency of data. Subsequently, the company refiled the application and the agency accepted the application this time around, assigning an FDA decision date of Dec. 24. The FDA also said it will hold an Adcom meeting ahead of the approval.

Brinavess, or vernakalant HCl in intravenous formulation, is an antiarrhythmic drug that’s being evaluated for the rapid onset atrial fibrillation to sinus rhythm for non-surgery patients. It has already been approved in Europe, Canada and other countries worldwide.

Inter-Cellular Expects Smooth Sailing For Schizophrenia Drug

• Company: Intra-Cellular Therapies Inc ITCI 1.22%
• Type of Application: NDA
• Candidate: Lumateperone
• Indication: Schizophrenia
• Date: Dec. 27

Lumateperone is Inter-Cellular’s lead product candidate that provides selective and simultaneous modulation of serotonin, dopamine and glutamate – three neurotransmitter pathways implicated in severe mental illness.

The initial PDUFA date of Sept. 27 was pushed back by three months after the company provided additional information to the FDA in response to the agency’s request related to non-clinical studies. Incidentally, the FDA also cancelled an Adcom meeting scheduled to discuss the NDA.

Later, following a meeting with the FDA, the company said the agency doesn’t plan to hold an Adcom meeting.

Amarin’s Vascepa Faces Final Hurdle After Unanimous FDA Panel Backing

• Company: Amarin Corporation plc AMRN 3.76%
• Type of Application: sNDA
• Candidate: Vascepa
• Indication: Reduce the risk of cardiovascular events
• Date: Dec. 28

An FDA panel that met in mid-November unanimously recommended approval of Vascepa to reduce the risk of cardiovascular events in high-risk patients.

Pfizer, Astellas Seek Label Expansion For Prostate Cancer Drug

• Company: Pfizer Inc. PFE 0.13% and ASTELLAS PHARMA/ADR ALPMY 1.16%
• Type of Application: sNDA
• Candidate: Xtandi
• Indication: prostate cancer
• Date: Fourth quarter

Xtandi capsules is an androgen receptor inhibitor initially approved for the treatment of patients with castration-resistant prostate cancer. The companies are now seeking approval of the drug for metastatic hormone-sensitive prostate cancer.

Can Allergan Get Relief With Migraine Drug Approval?

• Company: Allergan plc AGN 0.17%
• Type of Application: NDA
• Candidate: Ubrogepant
• Indication: migraine in adults
• Date: Fourth quarter

Ubrogepant is being evaluated for acute treatment of migraine in adults. The company announced FDA acceptance of the NDA in March, with the application submitted based on four clinical trials: two pivotal studies dubbed ACHIEVE 1 and ACHIEVE II and two additional studies.

Adcom Meetings

FDA’s Cardiovascular and Renal Drugs Advisory Committee will discuss on Dec. 10 Correvio’s NDA for Brinavess, or vernakalant HCl solution, ahead of the Dec. 24 PDUFA action date.

The Dermatologic and Ophthalmic Drugs Advisory Committee is scheduled to meet Dec. 13 to discuss Horizon Pharma Ireland Ltd.’s BLA for teprotumumab solution for intravenous use to treat active thyroid eye disease.

https://www.benzinga.com/general/biotech/19/11/14896078/attention-biotech-investors-mark-your-calendar-for-these-december-pdufa-dates