New anti-influenza drugs

Researchers at LSTM and Imperial College London have designed drugs which could help combat any potential new flu pandemic, by targeting the receptors of the cells by which the virus gains entry to the human body.

In a paper published today in the Journal of Immunology the team, led by LSTM’s Professor Richard Pleass, show that by engineering a part of an antibody they can target the viral proteins that allow flu to mutate and become so deadly to humans.

Last year marked the centenary of the 1918 influenza pandemic that claimed nearly 100 million lives worldwide, thus becoming the deadliest disease outbreak in recorded history. Global annual influenza outbreaks account for 300,000-650,000 respiratory deaths, mostly in children and the elderly.

Professor Pleass explained: “Influenza vaccines have limited public health impact during pandemics, and current influenza vaccines are less efficacious than vaccines for many other infectious diseases. This is because influenza viruses that circulate in human and animal populations mutate two key viral surface proteins, haemagglutinin (HA) and neuraminidase (NA), thus allowing them to escape from protective antibodies produced through natural infection or vaccination”

Both HA and NA target a sugar called sialic acid, that is found in abundance on the receptors of cells lining the mammalian respiratory tract, which the virus uses to gain entry into the body. The sialic acid-binding contacts on HA and NA do not mutate readily, otherwise the virus would not be able to infect human cells.

The team has engineered antibody Fc fragments with enhanced sialic acid that target these conserved parts of both HA and NA, binding influenza viruses and thus blocking their interactions with human cells.

By targeting sialic acid, these engineered biologicals may also be useful in the control of other pathogens, such as group B streptococci, Streptococcus pneumoniae, Mycoplasma genitalium, and Newcastle Disease Virus.

“Better anti-influenza therapeutics are urgently needed.” Continued Professor Pleass: “The transfer of antibodies from people recovering from influenza during the 1918 and 2009 pandemics reduced mortality from influenza by 50% and 26% respectively. However, to be useful, these antibody medicines (also called FLU-IVIG) need to be manufactured in advance of future epidemics, which is obviously problematic as there may be modest or little neutralising activity against newly emerging strains. Therefore, combinations of existing medicines, including FLU-IVIG, with sialic acid blockers could increase their efficacy while future-proofing against the next pandemic.”

Professor Sara Marshall, Head of Clinical and Physiological Sciences at the Wellcome Trust, who provided funding for this work, said: “This is a fascinating project, and one which could have really far-reaching impact not only for influenza but as a platform technology to develop new medicines for many other diseases that are currently treated by antibodies.”

The technology described is available for licensing.

---

Story Source:

Materials provided by Liverpool School of Tropical Medicine. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2019/01/190125120114.htm

Inconsistencies in Medicare off-label prescription list

If a patient has private insurance, doctors can get prior approval to prescribe a drug “off-label” to make sure the medication will be covered, but when it comes to Medicare part D, coverage decisions are dictated by two compendia — lists of medications and what they’re indicated for. Physicians have no way of checking for approval in advance, and if the compendia indicate coverage should be denied, there is no appeals process. Researchers from several institutions, including the Perelman School of Medicine at the University of Pennsylvania, examined these lists and found they are incomplete, outdated, and frequently in conflict with each other. They published their findings, as well as their call for new policy surrounding off-label coverage decisions, today in JAMA Dermatology.

Dermatologists often have good reason to prescribe a drug off-label, since the specialty deals with many rare and unique diseases, meaning evaluating treatments in randomized clinical trials may not always be feasible. Approximately a quarter of prescriptions for the ten most common dermatologic diagnoses are used off-label, and this percentage is likely higher for rare diseases. The compendia are meant to serve as a reference for which uses are medically accepted. If a medication is in the compendia, it’s approved. If it’s not, it’s rejected.

“There’s no real appeal process, so that rejection is the end of the story, and the rejection does not come with a suggestion of an alternative of what therapy might be approved instead,” said the study’s lead author John Barbieri, MD, a Dermatology Research Fellow at Penn. “This makes it incredibly challenging as a clinician, since we can find ourselves playing a guessing game while our patients wait for treatment.”

As a result, researcher set out to get a better understanding of what the compendia do include and whether they are sufficient for current clinical realities. They made a list of accepted treatments for 22 chronic, non-infectious diseases for which off-label prescribing is an important part of treatment. They then analyzed both compendia, the American Hospital Formulary Service (AHFS) Drug Information and the DRUGDEX® Information System for inclusion of these therapies.

Overall, they found just 73 of the 238 treatments they evaluated (31 percent) were included in either compendium. Among diseases, 10 of 22 (45 percent) had one or fewer treatments included in the DRUGDEX compendium, and 15 of 22 (68 percent) had one or fewer treatments included in the AHFS. For 53 out of 238 treatments (22 percent), the medication was included in one but not the other.

“The compendia don’t even agree with each other, and the literature they used as a basis for inclusion did not follow any discernable patter and was often based on decades old sources,” Barbieri said.

Just 56 percent (18 out of 32) of treatments with Grade A evidence (a double-blind study) were included in either compendium. The number dropped all the way down to 10 percent (3 of 30) for Grade B evidence (a clinical trial ? 20 Subjects), but went up to 12 percent (5 of 43) for Grade C evidence and 13 percent (8 of 61) for Grade D evidence. Results from randomized controlled trials were ignored while citations from single patient case-reports and even personal communication with pharmaceutical companies were included.

“It was not uncommon for first line therapies with a Grade A or B evidence to be missing from the compendia, while second or third line therapies with a lower evidence grade were included,” Barbieri said.

Researchers point out that the compendia are likely the most convenient way to make coverage decisions, but the inconsistencies that already exist combined with the rapid pace of new research and the more than 3,000 conditions managed by dermatologists means keeping them updated is logistically difficult. They propose two other potential solutions. One approach would require Medicare part D to consider evidence from literature that clinicians present during the authorization process. A second would be to develop an expert panel to review appeals for therapies not included in the compendia.

---

Story Source:

Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

---

Journal Reference:

1. John S. Barbieri, Kayla St Claire, Arash Mostaghimi, Joerg Albrecht. Evaluation of Clinical Compendia Used for Medicare Part D Coverage Determinations for Off-label Prescribing in Dermatology. JAMA Dermatology, 2019; DOI: 10.1001/jamadermatol.2018.5052

https://www.sciencedaily.com/releases/2019/01/190123112335.htm

Migraine’s link to higher stroke risk

Migraine with aura was associated with an increased risk of ischemic stroke in the Atherosclerosis Risk in Communities study, but a recent post-hoc analysis published in Headache reveals unexpected results suggesting that onset of such migraines before age 50 years is not associated with such risk. Later onset of migraine with aura was linked with a higher risk, however.

The analysis included 447 migraineurs with aura (MA) and 1,128 migraineurs without aura (MO) among 11,592 participants (elderly men and women with a history of migraine). Over 20 years, there was a twofold increased risk of ischemic stroke when the age of MA onset was 50 years or older when compared with no headache. MA onset before 50 years old was not associated with stroke. Also, MO was not associated with increased stroke risk regardless of age of onset.

In the elderly population in this study, the absolute risk for stroke in MA was 37/447 (8.27 percent) and in MO was 48/1,128 (4.25 percent).

“I think clinically this is very meaningful, as many individuals with a long history of migraine are concerned about their stroke risk, especially when they get older and when they have other cardiovascular disease risks,” said lead author Dr. X. Michelle Androulakis, Chief of Neurology at WJB Dorn VA Medical Center, in South Carolina. “Cumulative effects of migraine alone — with onset of migraine before age of 50 — did not increase stroke risk in late life in this study cohort. On the contrary, the recent onset of migraine at or after age 50 is associated with increased stroke risk in late life.”

---

Story Source:

Materials provided by Wiley. Note: Content may be edited for style and length.

---

Journal Reference:

1. X. Michelle Androulakis, Souvik Sen, Nishanth Kodumuri, Tianming Zhang, John Grego, Wayne Rosamond, Rebecca F. Gottesman, Eyal Shahar, B. Lee Peterlin. Migraine Age of Onset and Association With Ischemic Stroke in Late Life: 20 Years Follow-Up in ARIC. Headache: The Journal of Head and Face Pain, 2019; DOI: 10.1111/head.13468

https://www.sciencedaily.com/releases/2019/01/190124084828.htm

Lilly’s Oxtoby Jumps to Aimmune for Chief Commercial Officer Post

Aimmune Therapeutics (NASDAQ: AIMT) has appointed Andrew Oxtoby to serve as its chief commercial officer. Oxtoby comes to Brisbane, CA-based Aimmune after 16 years at Eli Lilly (NYSE: LLY), most recently as vice president of U.S. diabetes connected care and insulins. Aimmune is awaiting an FDA decision on its experimental peanut-allergy treatment, AR101.

https://xconomy.com/san-francisco/2019/01/23/eli-lillys-oxtoby-jumps-to-aimmune-for-chief-commercial-officer-post/

Indivior Granted Temporary Restraining Order on Generic Sublingual Film

Indivior PLC (LON: INDV) (“Indivior” or the “Company”) today announced that the U.S. District Court for the District of New Jersey has granted Indivior a temporary restraining order (TRO) that prevents Alvogen Pine Brook LLC (Alvogen) from launching its generic buprenorphine and naloxone sublingual film product.

This TRO will remain in place until February 7, 2019.

A Preliminary Injunction (PI) hearing will take place on that day.

“We are pleased that the District of New Jersey has granted Indivior’s motion for a TRO,” said Shaun Thaxter, CEO of Indivior. “We will continue to vigorously pursue our infringement cases against Alvogen to protect our SUBOXONE(R) (buprenorphine and naloxone) Sublingual Film patent portfolio, including continuing to pursue the appeal of the U.S. District Court for the District of Delaware’s non-infringement decision related to U.S. patents 8,603,514, as well as litigating our recently listed Orange Book patents for SUBOXONE(R) Film.”

https://www.marketscreener.com/INDIVIOR-19344116/news/Indivior-Is-Granted-Temporary-Restraining-Order-on-Generic-Sublingual-Film-27922447/

Patents asserted v. Janssen, Genmab in US declared invalid by summary judgment

Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the U.S. District Court of Delaware has declared the three U.S. patents (Nos. 8,263,746, 9,200,061, and 9,758,590), asserted by MorphoSys AG against Genmab and Genmab’s collaboration partner Janssen Biotech, Inc. (Janssen) are invalid by summary judgment.  The patent infringement lawsuit was initiated by MorphoSys against Genmab and Janssen in April 2016asserting that activities with DARZALEX (daratumumab) in the United States infringe its U.S. patents, and the case has been pending before the U.S. District Court of Delaware. The summary judgment order declared all three patents invalid due to lack of enablement.  As a result of this decision, the jury trial scheduled for February 2019 will not take place. MorphoSys has the opportunity to appeal the district court decision to the U.S. Court of Appeals for the Federal Circuit (CAFC). In addition, during the case a further claim by Janssen and Genmab was included in the case that the three MorphoSys patents were unenforceable due to inequitable conduct by MorphoSys. That issue remains to be decided.

https://www.marketscreener.com/GENMAB-1412914/news/Genmab-Announces-that-the-patents-asserted-against-DARZALEX-in-the-United-States-have-been-declar-27922534/

Apollo Hospitals Proton Cancer Centre inaugurated

Apollo’s Proton Cancer Centre (APCC) was inaugurated by Vice President Venkaiah Naidu, with Chief Minister ‘Edappadi’ K Palaniswami and several of his cabinet colleagues in attendance, on Friday.

The centre, said to be the first of its kind in south east Asia, is a 150-bed facility. Speaking at the launch, Venkaiah Naidu said, “The country, despite its fast growing economy, is facing many formidable challenges on the healthcare front.”

Inadequate public spending on healthcare, lack of penetration of health insurance and inadequate infrastructure in rural areas, are some of the issues plaguing the sector, he added.

When compared to standard radiation therapy, proton therapy is said to be able to offer a more targeted and precise approach to cancer, minimising damage to healthy tissues, resulting in fewer complications.

A statement from Apollo said that proton therapy is effective against many forms of cancer, particularly tumours affecting the eye and brain, tumours close to the brain stem, spinal cord, head and neck cancers, deep seated abdominal and pelvic cancers, recurrent cancers and paediatric cancers.

The launch of the proton centre is a defining movement in the country’s healthcare and also that of the world, said Prathap C Reddy, chairman, Apollo Hospitals group.

https://www.marketscreener.com/APOLLO-HOSPITALS-ENTERPRI-9058923/news/Apollo-Hospitals-Proton-Cancer-Centre-inaugurated-27922625/