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GlobalTort

The Intersection Among Torts, Science, Corporate Law, Insurance & Bankruptcy

Negligent Homicide – Navy Trial Ahead

Posted in Criminal Law and Torts

The lines between legal doctrines sometimes intersect. One of those intersections lies between tort law and criminal law. That intersection will be interesting to watch as the Navy proceedings move forward regarding the recent collisions between ships.  One also wonders about some of the collisions involving non-Navy ships.

As to the Navy proceedings, a January  17, 2018 Newsweek article provides an overview, and is pasted below:

“The former commanders of two U.S. Navy ships will face negligent homicide and other criminal charges in relation to accidents in the Pacific last year that left 17 sailors dead, Military Times reported Tuesday

Cmdr. Bryce Benson, who commanded the USS Fitzgerald when it was involved in a collision in June near Japan that killed seven sailors, will face charges of negligent homicide, dereliction of duty and hazarding a vessel. Three of Benson’s lieutenants will also face these charges. 

Cmdr. Alfredo J. Sanchez, who commanded the USS McCain when it was involved in a collision in August near Singapore that killed 10 sailors, will face the same charges as Benson. A chief petty officer from the McCain has also been charged with dereliction of duty.

“The announcement of an Article 32 hearing and referral to a court-martial is not intended to and does not reflect a determination of guilt or innocence related to any offenses. All individuals alleged to have committed misconduct are entitled to a presumption of innocence. Additional administrative actions are being conducted for members of both crews including non-judicial punishment for four Fitzgerald and four John S. McCain crewmembers,” the U.S. Navy said in a statement

These charges are the latest and perhaps most serious actions taken against officers involved in the deadly collisions, which were determined to be a result of human error. There have also been high level dismissals, including the firing of Vice Adm. Joseph Aucoin as head of the Japan-based 7th Fleet.

But what is “negligent homicide” and how does it pertain to the U.S. military?

Negligent homicide is the lowest level of criminal homicide in military law and carries a maximum sentence of three years in a military prison. It essentially is an accussation or charge of failing to exercise enough care for the safety of others. 

In a case early in the history of the U.S. Code of Military Justice (UCMJ)––federal law established by Congress that dictates military justice system and lists criminal offenses under military law––it stated, “[It] is our view that unlawful homicide through simple negligence is an offense under the Uniform Code of Military Justice,” according to the California Law Review at Berkeley Law Scholarship Repository

Negligent homicide falls under Article 134 of the UCMJ, which states, “Though not specifically mentioned in this chapter, all disorders and neglects to the prejudice of good order and discipline in the armed forces, all conduct of a nature to bring discredit upon the armed forces, and crimes and offenses not capital, of which persons subject to this chapter may be guilty, shall be taken cognizance of by a general, special or summary court-martial, according to the nature and degree of the offense, and shall be punished at the discretion of that court.”

In short, it is a serious charge but not the worst allegation a service member can face. 

In May 2017, a panel of seven U.S. Air Force officers found Senior Airman Benjamin Hann guilty of negligent homicide in connection to an incident in which Hann hit and killed Staff Sgt. Grant Davis with his car. Hann also pleaded guilty to two counts of dereliction of duty as well as one count of making a false official statement and one count of obstruction of justice. He was ultimately sentenced to four years in jail. “

 

“The coming of age of gene therapy: A review of the past and path forward”

Posted in Mass Tort Issues, Science

Advances in gene therapy are accelerating the pace and scale of the revolution in molecular biology. A new, open access review article in Science is very readable and helpful for a broad view of the history of the efforts, and a broad view of the history. The abstract sections are pasted below; the entire article is online here. Over time, the tools developed for this work will strongly influence personal injury and mass tort litigation.

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“Gene therapy: The power of persistence

Nearly 50 years after the concept was first proposed, gene therapy is now considered a promising treatment option for several human diseases. The path to success has been long and tortuous. Serious adverse effects were encountered in early clinical studies, but this fueled basic research that led to safer and more efficient gene transfer vectors. Gene therapy in various forms has produced clinical benefits in patients with blindness, neuromuscular disease, hemophilia, immunodeficiencies, and cancer. Dunbar et al. review the pioneering work that led the gene therapy field to its current state, describe gene-editing technologies that are expected to play a major role in the field’s future, and discuss practical challenges in getting these therapies to patients who need them.

Science, this issue p. eaan4672

Structured Abstract

BACKGROUND

Nearly five decades ago, visionary scientists hypothesized that genetic modification by exogenous DNA might be an effective treatment for inherited human diseases. This “gene therapy” strategy offered the theoretical advantage that a durable and possibly curative clinical benefit would be achieved by a single treatment. Although the journey from concept to clinical application has been long and tortuous, gene therapy is now bringing new treatment options to multiple fields of medicine. We review critical discoveries leading to the development of successful gene therapies, focusing on direct in vivo administration of viral vectors, adoptive transfer of genetically engineered T cells or hematopoietic stem cells, and emerging genome editing technologies.

ADVANCES

The development of gene delivery vectors such as replication-defective retro viruses and adeno-associated virus (AAV), coupled with encouraging results in preclinical disease models, led to the initiation of clinical trials in the early 1990s. Unfortunately, these early trials exposed serious therapy-related toxicities, including inflammatory responses to the vectors and malignancies caused by vector-mediated insertional activation of proto-oncogenes. These setbacks fueled more basic research in virology, immunology, cell biology, model development, and target disease, which ultimately led to successful clinical translation of gene therapies in the 2000s. Lentiviral vectors improved efficiency of gene transfer to nondividing cells. In early-phase clinical trials, these safer and more efficient vectors were used for transduction of autologous hematopoietic stem cells, leading to clinical benefit in patients with immunodeficiencies, hemoglobinopathies, and metabolic and storage disorders. T cells engineered to express CD19-specific chimeric antigen receptors were shown to have potent antitumor activity in patients with lymphoid malignancies. In vivo delivery of therapeutic AAV vectors to the retina, liver, and nervous system resulted in clinical improvement in patients with congenital blindness, hemophilia B, and spinal muscular atrophy, respectively. In the United States, Food and Drug Administration (FDA) approvals of the first gene therapy products occurred in 2017, including chimeric antigen receptor (CAR)–T cells to treat B cell malignancies and AAV vectors for in vivo treatment of congenital blindness. Promising clinical trial results in neuromuscular diseases and hemophilia will likely result in additional approvals in the near future.

In recent years, genome editing technologies have been developed that are based on engineered or bacterial nucleases. In contrast to viral vectors, which can mediate only gene addition, genome editing approaches offer a precise scalpel for gene addition, gene ablation, and gene “correction.” Genome editing can be performed on cells ex vivo or the editing machinery can be delivered in vivo to effect in situ genome editing. Translation of these technologies to patient care is in its infancy in comparison to viral gene addition therapies, but multiple clinical genome editing trials are expected to open over the next decade.

OUTLOOK

Building on decades of scientific, clinical, and manufacturing advances, gene therapies have begun to improve the lives of patients with cancer and a variety of inherited genetic diseases. Partnerships with biotechnology and pharmaceutical companies with expertise in manufacturing and scale-up will be required for these therapies to have a broad impact on human disease. Many challenges remain, including understanding and preventing genotoxicity from integrating vectors or off-target genome editing, improving gene transfer or editing efficiency to levels necessary for treatment of many target diseases, preventing immune responses that limit in vivo administration of vectors or genome editing complexes, and overcoming manufacturing and regulatory hurdles. Importantly, a societal consensus must be reached on the ethics of germline genome editing in light of rapid scientific advances that have made this a real, rather than hypothetical, issue. Finally, payers and gene therapy clinicians and companies will need to work together to design and test new payment models to facilitate delivery of expensive but potentially curative therapies to patients in need. The ability of gene therapies to provide durable benefits to human health, exemplified by the scientific advances and clinical successes over the past several years, justifies continued optimism and increasing efforts toward making these therapies part of our standard treatment armamentarium for human disease.”

 

 

Crime Scene DNA in Reverse – Using Genetics of Wild Animals to Hunt Down Poachers

Posted in Science

Hunting down poachers using genetic data from animals is a cool new use of genetic data; the idea arose from some creative thinking.  The strategy is outlined in a Janaury 9, 2018  NYT article by Gina Kolata. An excerpt is below.

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“[The poacher had]  jumped bail and fled to northern Pretoria, but it was vexingly difficult to catch and prosecute him — until a scientist helped make the case against him with rhino DNA.

His subsequent conviction resulted from a new tactic in wildlife preservation: The genetic fingerprinting methods that have been so successful in the criminal justice system are now being used to solve poaching crimes.

First, researchers in South Africa had to build a large database of genetic samples drawn from African rhinoceroses. The DNA would be used to match a carcass to a particular horn discovered on a suspected poacher or trafficker, or to rhinoceros blood on his clothes, knives or axes.

To make that possible, Dr. Cindy Harper, a veterinarian at the University of Pretoria, and her colleagues collected DNA from every rhinoceros they could find — more than 20,000 so far. They have taught park rangers how to retrieve blood, tissue or hair samples from every rhinoceros that is killed, dehorned or moved.”

An Example of Predicting/Finding Problems with New Drugs Using Proteomics (Biomarkers) – Work of SomaLogic

Posted in Drugs, Litigation Industry, Science

Pasted below is a fascinating press release from a proteomics company known as SomaLogic. The gist is the scientists were able to predict adverse effect problems with an experimental drug using SomaLogic’s molecular tools for measuring the amounts of proteins circulating in persons who were part of a clinical trial of the drug. The entire area of proteomics is fascinating and offers great potential for, among other things, better understanding of diseases and risks. This work by SomaLogic provides an exciting example of how new “omic” knowledge will create incredible changes in civil litigation issues. The full press release is pasted below and is well worth reading.

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“Protein changes in blood can provide early warning of potential harmful side effects from experimental drug candidates

In an article published “early online”in the American Heart Association journal Circulation, researchers at Pfizer, the Karolinska Institute, the University of California, San Francisco and SomaLogic describe how the measurement of blood-based protein changes in response to treatment with an experimental drug candidate may improve the efficiency and safety of clinical drug development. The published study used a nine-protein-based risk score to detect potential cardiovascular problems with a drug candidate (torcetrapib) well before significant adverse symptoms manifested themselves in patients in the drug’s clinical trial. Their analysis also identified changes in approximately 200 additional proteins that help describe the biology behind those adverse symptoms, which is applicable more broadly in cardiovascular disease management.

Pfizer’s phase three clinical trial (named “ILLUMINATE”) of torcetrapib, a drug candidate that had been shown to raise levels of “good”cholesterol and lower levels of “bad”cholesterol, was expected to confirm its blockbuster potential in reducing the risk of serious cardiovascular events such as heart failure and stroke. Instead, ILLUMINATE was halted abruptly in 2006 due to an unexpected increase in deaths and cardiovascular problems in trial subjects receiving the new drug candidate. At the time the trial was halted, Pfizer had invested 15 years and nearly a billion dollars in developing torcetrapib.
The Circulation study describes an attempt to determine if the problems from torcetrapib treatment could have been detected earlier, and thus at a lower cost. In this study, the researchers used the SOMAscan®assay to measure changes in the levels of over 1,000 proteins in blood samples from ILLUMINATE trial participants. Using a previously validated, nine-protein cardiovascular risk score, they found that they could successfully predict the harmful effects of torcetrapib in specific patients after only three months of treatment—much earlier than the point at which the ILLUMINATE trial was terminated (18 months).
In addition, a wider analysis of approximately 200 blood proteins that significantly changed in torcetrapib-treated patients revealed that the drug candidate had widespread, unexpected effects on normal immune and inflammatory processes. In addition, changes in only eight of the proteins measured were sufficient to explain the biology underlying the hypertension side effect seen in clinical trials. Beyond torcetrapib, these insights can also provide additional guidance for more personalized and targeted prescribing of currently marketed cardiovascular drugs, such as statins and ACE inhibitors.
Torcetrapib is just one member of a promising class of cardiovascular disease-prevention drugs, cholesteryl ester transferase (CETP) inhibitors, that have garnered considerable interest from the pharmaceutical industry. In addition to Pfizer, both Eli Lilly and Roche had candidate CETP inhibitors that were dropped late in development due to lack of efficacy. However, Merck recently announced that their drug candidate anacetrapib successfully completed the longest CETP clinical trial to date.

Expanding the work described in the Circulation paper to include comparative analyses from all of these drug candidate trials from different companies could provide, not only enhanced understanding of critical protein changes related to side effects, but could also reveal early signs of “positive”protein changes that would help accelerate the successful development of more promising candidates from not only this drug, but across many different classes and even disease types.

Reference: Williams, SA et al. (2017) “Improving Assessment of Drug Safety Through Proteomics: Early Detection and Mechanistic Characterization of the Unforeseen Harmful Effects of Torcetrapib” Circulation (published early online October 3, 2017).
Contact:
Fintan R. Steele, Ph.D.
Chief Communications Officer
T: 720-214-3080
C: 617-816-9834
fsteele@somalogic.com

About SomaLogic

SomaLogic is committed to helping people worldwide receive timely, accurate, trustworthy and actionable information that helps them manage their personal health and wellness. To realize this vision, we are creating and delivering the ”SOMAscan Platform,”a clinically useful and affordable health information system based on comprehensive and personalized protein measurement, delivered broadly through a global ecosystem of partners and users.

“FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss”

Posted in Science

The molecular revolution continues to expand. Some of the new evidence arises from the FDA’s December 19, 2017 approval of a therapy based on gene editing for vision loss resulting from inherited gene defects. The FDA’s December 19, 2017 press release is pasted below and highlighted to emphasis implications for the future.

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December 19, 2017

Summary
FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss

Release
The U.S. Food and Drug Administration today approved Luxturna (voretigene neparvovec-rzyl), a new gene therapy, to treat children and adult patients with an inherited form of vision loss that may result in blindness. Luxturna is the first directly administered gene therapy approved in the U.S. that targets a disease caused by mutations in a specific gene.

“Today’s approval marks another first in the field of gene therapy — both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss — and this milestone reinforces the potential of this breakthrough approach in treating a wide-range of challenging diseases. The culmination of decades of research has resulted in three gene therapy approvals this year for patients with serious and rare diseases. I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses,” said FDA Commissioner Scott Gottlieb, M.D. “We’re at a turning point when it comes to this novel form of therapy and at the FDA, we’re focused on establishing the right policy framework to capitalize on this scientific opening. Next year, we’ll begin issuing a suite of disease-specific guidance documents on the development of specific gene therapy products to lay out modern and more efficient parameters — including new clinical measures — for the evaluation and review of gene therapy for different high-priority diseases where the platform is being targeted.”

Luxturna is approved for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy that leads to vision loss and may cause complete blindness in certain patients.

Hereditary retinal dystrophies are a broad group of genetic retinal disorders that are associated with progressive visual dysfunction and are caused by mutations in any one of more than 220 different genes. Biallelic RPE65 mutation-associated retinal dystrophy affects approximately 1,000 to 2,000 patients in the U.S. Biallelic mutation carriers have a mutation (not necessarily the same mutation) in both copies of a particular gene (a paternal and a maternal mutation). The RPE65 gene provides instructions for making an enzyme (a protein that facilitates chemical reactions) that is essential for normal vision. Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. Individuals with biallelic RPE65 mutation-associated retinal dystrophy experience progressive deterioration of vision over time. This loss of vision, often during childhood or adolescence, ultimately progresses to complete blindness.

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal protein that converts light to an electrical signal in the retina to restore patient’s vision loss. Luxturna uses a naturally occurring adeno-associated virus, which has been modified using recombinant DNA techniques, as a vehicle to deliver the normal human RPE65 gene to the retinal cells to restore vision.

“The approval of Luxturna further opens the door to the potential of gene therapies,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Patients with biallelic RPE65 mutation-associated retinal dystrophy now have a chance for improved vision, where little hope previously existed.”

Luxturna should be given only to patients who have viable retinal cells as determined by the treating physician(s). Treatment with Luxturna must be done separately in each eye on separate days, with at least six days between surgical procedures. It is administered via subretinal injection by a surgeon experienced in performing intraocular surgery. Patients should be treated with a short course of oral prednisone to limit the potential immune reaction to Luxturna.

The safety and efficacy of Luxturna were established in a clinical development program with a total of 41 patients between the ages of 4 and 44 years. All participants had confirmed biallelic RPE65 mutations. The primary evidence of efficacy of Luxturna was based on a Phase 3 study with 31 participants by measuring the change from baseline to one year in a subject’s ability to navigate an obstacle course at various light levels. The group of patients that received Luxturna demonstrated significant improvements in their ability to complete the obstacle course at low light levels as compared to the control group.

The most common adverse reactions from treatment with Luxturna included eye redness (conjunctival hyperemia), cataract, increased intraocular pressure and retinal tear.

The FDA granted this application Priority Review and Breakthrough Therapy designations. Luxturna also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The sponsor is receiving a Rare Pediatric Disease Priority Review Voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive Priority Review of a subsequent marketing application for a different product. This is the 13th rare pediatric disease priority review voucher issued by the FDA since the program began.

To further evaluate the long-term safety, the manufacturer plans to conduct a post-marketing observational study involving patients treated with Luxturna.

The FDA granted approval of Luxturna to Spark Therapeutics Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.