Endo Has A Huge Opportunity — And Allergan May Want A Piece of It

Endo Pharmaceuticals (ENDP) is closing in on a $400 million opportunity for treating cellulite in the U.S. — and that could prompt top dog Allergan (AGN) to seek a partnership, an analyst said Tuesday.

There was significant interest on Endo’s second-quarter earnings conference call about its drug, called collagenase clostridium histolyticum, or CCH, for cellulite treatment. Cellulite occurs when connective tissue under the skin, made of collagen, hardens and contracts, causing dimples.

Cellulite affects 80%-90% of women post puberty. Endo’s drug aims to break the collagen tethers to release the dimples and, potentially, smooth the skin. Mizuho analyst Irina Koffler says there are a number of reasons for Allergan to seek a partnership to market CCH internationally.

“Allergan could get global rights to this product, which may drive revenue synergies with its other body contouring assets and facial injectables,” she said in a note to clients. “We believe that Allergan already has all of the necessary commercial infrastructure to market CCH Cosmetic.”

Further, Allergan is soon to face competition from Evolus (EOLS), which is making an injectable drug that could rival massive moneymaker Botox. As such, Allergan would benefit “from a new and innovative product to introduce to physicians in 2020,” she said.

Cellulite Treatment Rivalries

Endo is testing CCH Cosmetic in Phase 3 studies. Results are expected in late 2018. The market is already saturated with rival products from Allergan and Hologic (HOLX), but none have 100% customer satisfaction, Mizuho said.

“We learned that doctors categorize cellulite treatment as either relatively effective (but expensive and debilitating) or less invasive and less effective,” she said.

Cellfina, a cellulite treatment from privately held Merz Pharmaceuticals, costs $4,000-$6,000 and provides durable results. But it comes with pain, bruising and very specific recovery instructions. One website notes 73% of Cellfina patients surveyed say it’s worth it. Allergan’s drugs, Kybella and Botox, have 75% and 95% worth-it ratings.

In contrast, Hologic’s Cellulaze only has a 33% satisfaction rating, due to lacking effectiveness.

Challenges In Cellulite

An expert cited by Koffler says he’s already tried Endo’s drug, Xiaflex, as an off-label cellulite treatment. Xiaflex is the branded name for CCH when used to treat scar tissue in the hand and in male genitalia. He says Xiaflex could prove to be overzealous in severing collagen tethers.

“There are other fibrous (connective tissues) that provide support and structure to the skin,” Koffler said. “Physicians have had negative prior experience with an existing laser that destroyed the underlying structural support to the skin and cause skin laxity.”

Other physicians have noted the same concern, Koffler said. They say it’s difficult to treat cellulite without knowing where the collagen tethers are in relation to the dimples.

Endo says there are no approved devices to visualize the tethers. The firm also said it hasn’t seen laxity problems in testing.

Market Opportunity In Cellulite

The market opportunity in cellulite is significant, Koffler said. Physicians say cellulite can lead to eroding self confidence in women.

Koffler sees the opportunity for CCH Cosmetic to be in line with Allergan’s CoolSculpting, which aims to improve the appearance of double chins.

“Because of the significant sales of topical agents and noninvasive products, our (key opinion leader) believes that a product that produces a noticeable improvement in the appearance of cellulite, and is economical and has a short recovery time would be ‘wildly popular,'” Koffler wrote.

At the same time, these treatments are unlikely to be as popular as liposuction, the doctor said.

https://bit.ly/2MkIQNZ

Acid-suppression meds overused in ICU

Gordon Guyatt and Deborah Cook’s recent New England Journal of Medicine review of prophylaxis for upper gastrointestinal bleeding among hospitalized patients explains that not only is acid suppression commonly used without indication in the intensive care unit (ICU) and medical wards, but these medications are frequently continued after discharge. For example, studies have shown that ~60% of patients transferred from the ICU to the wards were continued on prophylactic acid suppression without indication.

The article also reviews some of the potential adverse effects of unnecessary acid suppression, including chronic kidney disease, osteoporosis, and infections. We agree with their Slow Medicine conclusion that prophylactic acid suppression is often “used for critically ill patients at low risk [of bleeding] and for many hospitalized patients who are not critically ill and have a very low risk of bleeding … For low-risk patients in the ICU, in medical and surgical units … use of acid suppression in the absence of a clear indication for it may confer a net harm.”

The overuse of acid-suppressing medications is not limited to the inpatient setting, however. A series of studies have also demonstrated that roughly 50% of outpatients on chronic proton pump inhibitors (PPIs) do not have indications for these medications.

So the question arises: how should we approach “deprescribing” PPIs? Anecdotally, we have not had much success with simply recommending that patients stop cold turkey. In part this is due to rebound acid hypersecretion, which begins ~2 weeks after stopping PPIs and can last for months until acid production returns to normal. Fortunately, the Canadian Family Physician recently published an evidence review with some tips. While the authors find there is little solid evidence to recommend one approach over another when deprescribing PPIs, what is clear is that we should consider several options, including a gradual dose decrease, spacing out dosing to every other day, or switching to “as needed” use.

Another option is a “step-down” approach in which patients are transitioned to H2 blockers or antacids; there is some evidence from the DIAMOND trial to support this strategy. These options are clearly laid out for clinicians in a complementary review by the Canadian Therapeutics Initiative.

https://bit.ly/2Mdvh3v

How to Fight Misinformation in Healthcare

“Fake news” is a term that’s become notorious over the last couple of years — for notorious reasons, perhaps. But there’s actually another serious area where there is inadvertently an awful lot of “fake news” on a daily basis. And that is, well you guessed it: in healthcare throughout our nation’s hospitals and offices.

Let me explain, and I suspect anyone who works in healthcare will be familiar with the scenario. A physician or nurse assumes care of a new patient and a huge amount of information is thrown their way. They have “coronary artery disease,” they “drink five beers a day,” they “take a steroid pill every day,” they “will be discharged to rehabilitation.” All sounds like very serious stuff. However, in years of being a practicing physician, there is one rule I always follow: Take everything with a grain of salt until you actually sit down and talk directly with the patient.

I have written a lot about the problems that electronic medical records have caused at the frontlines of healthcare. I am not going to make this another rant on the topic. However, I will say this: information technology is currently the number one reason for the propagation of fake news in healthcare. And this has serious implications for patients — who must always be sure to double check that their physician is aware of their accurate history. God knows what is on the computer and what old information is still being banded around about you. Physicians, for our part, are sadly fast losing the art of simply talking with our patients. No matter where technology takes us, there’s no substitute for this.

I used to be heavily involved in educating residents and medical students before I had to cut back over the last couple of years owing to my other commitments. I recall several situations that I would hazard a bet take place every day in our teaching hospitals. A classic example went something like this (and I usually just let the situation unfold before I respond in a tongue-in-cheek way): I am the teaching attending and we are huddled around a computer. After a result comes back, the residents start debating what antibiotic to put the patient on. They had information that the patient was “allergic to a couple of major antibiotics.” This had come from the computer and from their printed piece of paper.

Here’s a group of young intelligent doctors and medical students. They brainstorm and it’s clear our choices are limited. I listened to them and finally said, “You know what, we are about 30 feet away from the patient’s room. Have any of you actually gone in to talk to the patient about their allergy history and confirm what really happened?” Sure enough, nobody has! That was perhaps all too much work and common sense (I say in a semi-derogatory but mentor-like way). When I send one of them in to go and confirm with a face-to-face conversation — turns out that none of the antibiotics were true allergies, and we were fine starting one of them. I’ve seen this happen more times than I can even remember. There are countless other examples I can also recall: whether the patient is or isn’t a drinker, whether they cut their pill in half, whether they did or didn’t have a flu vaccination. So much fake news all around!

It is my firm belief that misinformation in healthcare, especially in the age of electronic medical records, is dangerous. The only sure-fire way to combat all this — whether you are a doctor, nurse, or even a patient — is to communicate directly the good old-fashioned way and not believe what you hear until you diligently confirm it yourself.

Suneel Dhand is an internal medicine physician and author. He is the founder of DocSpeak Communications and co-founder of DocsDox, and blogs at his self-titled site, Suneel Dhand.

https://bit.ly/2OBa2oO

Orchard raises $150m to develop gene therapies

Biotech Orchard Therapeutics has raised $150m to further develop its three most advanced rare disease gene therapies.

Earlier this year GlaxoSmithKline handed over its rare disease gene therapy pipeline to Orchard, along with the already approved Strimvelis, for adenosine deaminase severe combined immunodeficiency (ADA-SCID) – the immune disorder known as “bubble boy syndrome”.

GSK also took a 20% stake in the company and Orchard is looking to progress development of its three most promising pipeline drugs – gene therapies OTL-101 for ADA-SCID, OTL-200 for metachromatic leukodystrophy (MLD) and OTL-103 for Wiskott Aldrich syndrome.

Funding will also support clinical and preclinical development of other rare disease drugs in Orchard’s pipeline.

Orchard also has a drug for X-linked chronic granulomatous disease (X-CGD) and transfusion dependent beta-thalassemia (TDBT) in the clinic.

Deerfield Management led the Series C financing, with significant cash from new investors including RA Capital Management, Perceptive Advisors,  and Ghost Tree Capital Group.

Existing investors also participated including Temasek, Baillie Gifford, RTW Investments, LP, Cowen Healthcare Investments and Agent Capital.

Mark Rothera, president and CEO of Orchard, said: “We are thrilled to have such strong support from both new and existing investors in this financing round.”

“The quality of this investor syndicate is a testament to the confidence we have built among our stakeholders, based on the substantial progress of Orchard’s clinical and preclinical programs since our Series B round last year.”

Elise Wang, Principal at Deerfield Management, said: “Orchard has made an impressive transition from a start-up company to an emerging leader in gene therapy for rare diseases by building a comprehensive, industry-leading portfolio of ex vivo gene therapies and assembling a highly experienced team.  We are pleased to have led this round of financing. We believe the company has generated compelling clinical data on products which have the potential to become breakthrough treatments for patients.”

https://bit.ly/2w5qQgh

Nebraska resorts to fentanyl in execution, despite appeal from pharma

Nebraska is to become the first US state to use the opioid fentanyl in an execution – after an appeals court threw out a legal challenge from the German drug maker Fresenius Kabi.

The court gave the go ahead yesterday for Nebraska to execute Carey Dean Moore on the grounds that it is the “will of the people”, The Guardian reported.

This is Nebraska’s first execution in 21 years after 61% of the voters in the state voted to reinstate the death penalty two years ago, after the state government abolished it.

Moore has been on death row for four decades for the 1979 murders of two cab drivers in Omaha.

Fentanyl was implicated in more than 20,000 overdose deaths in 2016 alone – but Nebraska has opted to include it in the lethal injection cocktail for its first execution in 21 years after struggling to buy pharmaceuticals for use in the procedure.

Many pharma companies have set up special distribution arrangements for certain drugs to prevent their use in lethal injections.

Moore said he wishes to die and is among the longest serving prisoners on death row in the US.

He will be given the sedative Valium alongside fentanyl, a combination that is often found in drug overdose deaths – both drugs suppress breathing.

Fresenius accuses Nebraska of obtaining the other two drugs in the cocktail illegally – a muscle relaxant and potassium chloride to stop Moore’s heart.

The company takes no position on the death penalty but said contracts with distributors bar sales for use in capital punishment.

There is a risk of grave harm to its reputation, the company said, because the state has not properly stored the drugs, which could lead to a botched and painful execution.

The human rights charity Reprieve has been campaigning against the death penalty, and has criticised the lethal injection as a form of torture.

Lethal injections usually consist of three components – an anaesthetic to send the subject to sleep, before a paralytic agent (such as pancuronium bromide) is administered to prevent thrashing during the final dose of potassium chloride to stop the heart.

But the charity has raised concerns that the injection could be seen as a form of torture, as subjects can experience extreme levels of pain should the first injection not work properly.

The charity’s director Maya Foa has described the lethal injection as “the chemical equivalent of burning at the stake”.

https://bit.ly/2vLGsGj

UnitedHealthcare weighs options after losing NY risk adjustment pay suit

UnitedHealthcare said it is evaluating its options after a federal judge in New York dismissed a lawsuit brought by the insurer and Oxford Health Insurance against the state Department of Financial Services over the constitutionality of risk adjustment payments.

“We respectfully disagree with the court’s decision and are evaluating our options,” UnitedHealthcare said by statement.

The insurers filed the lawsuit last year over a modification to the federal risk adjustment program implemented by the U.S. Department of Health and Human Services in New York. The regulation allowed DFS Superintendent Maria Vullo to collect up to 30 percent of funds received from insurers and redistribute them to other insurers based on the state’s own methodology, according to the New York Law Journal.

The insurers said the methodology used by the state was an unconstitutional taking of their property, according to the court decision of August 11. UnitedHealth and Oxford said the DFS did not have the authority to take their funds and redistribute them, as the state regulation is preempted by the federal risk adjustment program.

U.S. District Court Judge John Koeltl of the Southern District of New York disagreed, saying the U.S. Department of Health and Human Services allows states to adjust the federal program. The judge granted the state’s motion to dismiss.

“DFS is pleased that the federal court has recognized the superintendent’s authority to promulgate New York’s health insurance risk adjustment regulation and to enforce state law through regulation to protect New York’s markets and consumers,” Vullo said by statement. “This decision correctly upholds New York’s regulatory insurance authority and clearly affirms that New York’s continued enforcement of New York insurance law and regulation is not preempted by federal law.”

Risk adjustment, established under the Affordable Care Act, is a budget neutral program that collects payments from insurers in the market and redistributes the funds to payers that cover higher risk individuals.

https://bit.ly/2vLF86j

Give your child a head start in math

Many kids struggle with math — and for a number of reasons.

Knowing when to be concerned will allow you to get your child study help early on, which is important because research shows that young children who have difficulty with math typically will continue to struggle as they get older.

Signs of math difficulties can start as early as 2 years of age. Unlike the terrible 2s, however, this is not something they grow out of. For preschool children, risk factors for math struggles include low cognitive functioning, vocabulary difficulties, and being from a low socioeconomic household.

For elementary- and middle-school children, risk factors for math struggles include reading, math and attention-related behavioral difficulties, as well as being from a lower socioeconomic household.

Attending preschool or Head Start can lower the risk of math struggles. Screening and intervention efforts as soon as a child starts school also help. Kids should be assessed for math, reading and even behavior problems.

Help your kids get comfortable with math as early as possible. Play informal counting games, like counting the forks and spoons in your kitchen, or the cans and boxes as you unpack groceries. Make a game of looking for a certain number as you read the pages of a book. These activities help lay the groundwork for future classroom success.

And make sure you feel comfortable with math yourself. Kids of math-anxious parents often learn less math at school and are more likely to become math-anxious themselves when their mom or dad repeatedly tries to help with homework.

Resist verbalizing any dislike you have of math in front of your child. Instead use tools like computer and board games and even apps to help you interact in a more positive way.

You might even start to like math yourself.

More information

GreatSchools.org has seven secrets to get kids excited about math with help from mom and dad.

https://bit.ly/2Moj0Zj