Lilly partners with AC Immune for Alzheimer’s treatment

Eli Lilly & Co and AC Immune SA have agreed to jointly develop a potential treatment for Alzheimer’s disease.

Under the terms of the deal, AC Immune will receive an upfront payment of 80 million Swiss francs ($80.47 million) and $50 million in exchange for a note convertible to equity at a premium, the companies said on Wednesday.

https://www.reuters.com/article/us-lilly-alzheimers-ac-immune/lilly-partners-with-ac-immune-for-alzheimers-treatment-idUSKBN1OB18F

More people having cataract surgery at a younger age

If you think cataracts are an eye ailment only afflicting people 70 or older, think again. More younger patients are getting cataracts and having cataract surgery than ever, according to Dr. Ming Wang, an ophthalmologist in Nashville.

Linda Bowman, 54, is a good example. Bowman, who lives in Cedar Falls, Iowa, and works for a senior living community, says she was shocked when diagnosed with cataracts in both of her eyes at 51. “I was in disbelief, and I suddenly felt 20 years older because I had never heard of someone younger having cataract surgery. I always envisioned people in their 70s or 80s,” she says.

Another reality added to Bowman’s shock about her diagnosis: Her 80-year-old father had just undergone cataract surgery, while her mother underwent a cataract operation in her early 70s.

“My doctor kept telling me it’s not a sign of age. It’s just something you need done in your eyes,” she recalls.

Wang says he’s noticed a dramatic uptick of younger cataract surgery patients: “It’s a national trend that’s been happening in the last 20 years.”

Cataracts, a clouding of the normally clear lens of the eye, can start in people in their 40s, although they won’t likely be noticeable. As a person ages, a cataract can grow to the point where it impairs vision in the eye. For example, night driving might become more difficult, halos of glare may be reflected in headlights and vision may be cloudy.

So, if cataracts don’t usually become problematic until a patient is in his or her later years, why are people in their 50s and 60s undergoing cataract surgery with more frequency today?

Cataract surgery: changing expectations and technology

According to Wang, who has performed more than 20,000 cataract surgeries since 1993, there are several reasons. For one, patient expectation has changed over the past 30 years.

It used to be that “patients only had cataract surgery if they couldn’t see even with glasses, which significantly debilitated their daily function. But today, patients undergo cataract surgery when their vision, even with glasses, imposes only a moderate impact on their daily lives. They want to see better with less dependence on glasses,” Wang says.

Numerous advancements in technology during the last 30 years also have made cataract surgery less daunting, he says. There used to be more risk associated with the surgery and outcomes were not as good as they are today.

Another potential reason for the uptick in cataract surgeries among people in their 50s and 60s could be a more active lifestyle with more time spent outdoors, says Dr. David Aizuss, an ophthalmologist in Encino, Calif.

Aizuss, the newly elected president of the California Medical Association, says increased exposure to the sun can lead to cataracts. Wearing sunglasses or other protective gear to block the sun’s harmful rays from the eyes can help to prevent early onset of cataracts.

Some other ways to help prevent cataracts include not smoking; controlling other diseases, such as diabetes and eating a healthy diet that includes leafy green vegetables, fruits and foods high antioxidants, according to the American Optometric Association and the National Eye Institute. The National Eye Institute also recommends that people 60 and older have a comprehensive dilated eye exam at least once every two years.

Benefits of cataract surgery in your 50s or 60s

If you’re in your 50s or 60s, you’re no doubt unhappy to hear about the trend toward more cataracts in your age group. But you can at least take heart knowing there are some benefits to having the surgery at a younger age. For example, younger cataract surgery patients enjoy improved vision for more years than older patients.

If you have cataracts, “What’s the point of waiting until 84, 94, to have the surgery?” Wang says. “You want to be able to enjoy better vision for a longer period of time.”

Younger patients also tend to heal more quickly than older ones, he says. They generally resume their normal level of activity more rapidly than older patients, too, which helps develop a positive attitude imperative for a speedy recovery.

Although Bowman was anticipating improved vision following her cataract operations, she was conflicted about having them. Calling the emotional strife she suffered following her diagnosis of cataracts at 51 as the “most challenging” aspect of her entire experience, she says, in hindsight, the best response is to laugh about it.

Bowman says she loves that she can see much better since her cataract surgery. She has also gained another, and unexpected, type of perspective from her operation: “It made me more empathic because I work with older people.”

https://www.marketwatch.com/story/why-the-increase-of-cataract-surgery-in-younger-people-2018-12-12?siteid=rss&rss=1

BioXcel Therapeutics announces FDA acceptance of IND for BXCL501

BioXcel Therapeutics announced that the FDA has accepted its Investigational New Drug, or IND, application for lead neuroscience candidate, BXCL501. BTI plans to evaluate BXCL501, a proprietary sublingual thin-film formulation of dexmedetomidine in a first-in-human pharmacokinetic and safety study in healthy volunteers. BTI is a clinical-stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology. The IND-opening Phase 1 study is a placebo-controlled, single-dose, dose-escalation study of BXCL501 that is expected to enroll up to 60 healthy adult volunteers across various dosing groups. The primary endpoints are pharmacokinetics and safety, with secondary endpoints including assessment of pharmacodynamics, or PD, and the relationship between BXCL501 concentrations and PD endpoints. The company expects to report top-line data from the study in the first half of 2019 that will provide a path for BTI to launch the anticipated registration studies.
https://thefly.com/landingPageNews.php?id=2835741

Top Ten Drugs Tied to Overdose Deaths

Deaths from drug overdose in the United States increased by 54% from 2011 to 2016 — with opioids, benzodiazepines (benzos), and stimulants the most commonly used drug classes involved, a new report released today by the Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS), shows.

The report notes that there were 41,340 drug overdose deaths in 2011 vs 63,632 such deaths in 2016.

Although the opioid oxycodone was the most cited drug in overdose death records in 2011, heroin took the top spot from 2012 to 2015.

The story around fentanyl may be even more troubling. The rate of overdose deaths involving it or one of its analogs doubled each year from 2013 through 2016, when it finally took the lead in becoming the most mentioned drug. In 2016, 29% of all overdose deaths involved fentanyl (n = 18,335).

In addition, the stimulant cocaine was the second or third most cited drug in the overdose death records throughout the entire study period.

The CDC’s list of the 10 most frequently mentioned drugs also included the opioids methadone, morphine, and hydrocodone; the benzos alprazolam and diazepam; and the stimulant methamphetamine.

Of all 10 drugs, only methadone was associated with a decreasing overdose death rate from 2011 to 2016.

“While the ranking changed from year to year, the top 10 drugs involved in overdose deaths remained consistent throughout the 6-year period,” note the investigators, led by Holly Hedegaard, MD, NCHS.

“This report identifies patterns in the specific drugs most frequently involved in drug overdose deaths…and highlights the importance of complete and accurate reporting in the literal text on death certificates,” they write.

The data were published online in the December 12 issue of the National Vital Statistics Reports.

Rise in Overdose Death Toll

An NCHS report released last year showed the age-adjusted rate of US drug overdose deaths increased dramatically from 1999 (6.1 per 100,000 population) to 2016 (19.8 per 100,000).

Although several previous studies on drug overdoses have used National Vital Statistics System-Mortality (NVSS-M) information, this data is coded using the International Classification of Diseases, Tenth Revision (ICD-10); and these ICD-10 codes focus on broad drug categories rather than on individual drugs, note the investigators.

In answer to this, the NCHS and the US Food and Drug Administration “collaboratively developed methods to search the literal text from death certificates to identify mentions of specific drugs and other substances, and to search contextual terms to identify involvement of the drug(s) or substance(s) in the death,” the researchers write.

They defined “literal text” as written information from the medical certifier on cause or circumstances related to a death.

For the current report, they examined NVSS-M data from 2011 through 2016. These data were linked to electronic files containing death certificate information.

In addition to the top 10 drugs involved in overdose deaths, drugs that held the number 11 through number 15 ranking throughout the 6-year study period included diphenhydramine, acetaminophen, citalopram, carisoprodol, oxymorphone, tramadol, amitriptyline, clonazepam, gabapentin, and amphetamine.

Threefold Increase in Heroin Deaths

The involvement of heroin in overdose deaths rose threefold from 4571 deaths in 2011 to 15,961 deaths in 2016. This made it the second-most mentioned drug in 2016, behind fentanyl.

Mentions of cocaine increased from 5892 overdose deaths in 2014 to 11,316 deaths in 2016, giving it that year’s number 3 ranking.

The fourth most mentioned drug in overdose deaths in 2016 was methamphetamine. Its 6762 related deaths signified a sharp increase from the 1887 related deaths in 2011.

“An analysis of trends…showed that, for several drugs, the age-adjusted rate of drug overdose deaths increased considerably within a relatively short period,” the investigators write.

Heroin, cocaine, and methamphetamine all showed significant increasing trends for age-adjusted rates of drug overdose deaths between 2011 and 2016 (1.5 vs 5.1 per 100,000 population; 1.6 vs 3.6 per 100,000; and 0.6 vs 2.1 per 100,000, respectively; all, P < .05).

Fentanyl showed a significant increasing trend between 2013 and 2016 (0.6 vs 5.9 per 100,000; P < .05).

The only decrease for a specific drug came from methadone, which was mentioned in 4545 overdose deaths in 2011 vs 3493 deaths in 2016 (1.4 vs 1.1 per 100,000). Still, it was the eighth most mentioned drug in 2016.

For the 2016 top 10 drugs, “the proportion of deaths involving both the referent drug and at least one other concomitant drug ranged from 50% for methamphetamine to 96% for alprazolam or diazepam,” the researchers report.

Finally, drugs most frequently recorded in unintentional overdose deaths in 2016 were fentanyl, heroin, and cocaine. The most frequently cited drugs in suicide by overdose were oxycodone, diphenhydramine, hydrocodone, and alprazolam.

NCHS National Vital Statistics Reports. Published December 12, 2018. Full text

https://www.medscape.com/viewarticle/906434#vp_1

GlaxoSmithKline’s Shingrix shortage expected to persist ‘throughout 2019’

In the face of “unprecedented” demand for its shingles vaccine, GlaxoSmithKline is doing everything it can to boost supply. But in spite of those efforts—it shipped as much vaccine in the third quarter as it did in the first half of the year—GSK says the Shingrix shortage will persist into 2019.

Over the next two to three years, the company intends to significantly boost shipments to the U.S., with plans to grow its overall capacity to the “high teen millions” annually, spokesman Sean Clements said.

But for now, the unexpected uptake for the vaccine in the U.S. has overwhelmed the company’s ability to keep up, forcing it to take steps like implementing order limits and delaying TV advertising.

“Because healthcare professionals continue to vaccinate at a rate many times that of previous years, we expect ordering limits to continue throughout 2019 to help us ensure that vaccine is distributed fairly and equitably where it is needed,” Clements added.

GSK makes the shots, which take 6 to 9 months to produce, at a plant in Belgium. In the face of an expected approval, GSK had stockpiled some “critical elements” to shorten production timelines after approval. Even with that effort, the company hasn’t been able to keep up with demand. For consumers, the shortage means pharmacies have long wait lists or no wait lists at all, according to reports.

GlaxoSmithKline’s new shingles vaccine won U.S. approval last fall and has surpassed early sales estimates. About 7 million doses had been administered as of September. For 2018, the company is expecting £700 million to £750 million in sales for Shingrix.

The vaccine supplanted Merck’s Zostavax on the market and has seen higher demand than its predecessor due to its strong efficacy. Plus, U.S. vaccine advisers recommended Shingrix for people 50 and older, giving GSK a target population of 115 million adults, executives have said.

“We need to get the supply expanded as fast as possible, because we can pretty much sell anything that we can make now in the U.S.,” GSK’s Luke Miels, global pharmaceuticals president, told analysts on the company’s third-quarter conference call.

As the shortage continues, GSK has held off on TV advertising for the product.

https://www.fiercepharma.com/pharma/glaxosmithkline-shingrix-shortage-expected-to-persist-throughout-2019-cdc-says

As competition heats up, U.S. prices for Remicade and biosims slip

As Johnson & Johnson vies with biosimilars to its big-selling Remicade, prices across the category are gradually falling, an analyst says—and Pfizer’s Inflectra has taken the biggest tumble.

The J&J therapy is among just a few biologics facing off against biosimilars in the U.S. While the company initially had success holding off the new entrants, competition is finally dragging down the brand and its biosims.

Bernstein analyst Ronny Gal wrote Monday that Remicade prices are down 10.7% year over year, compared with 24.2% for Pfizer’s biosimilar version, Inflectra, and 18% for Merck’s biosim Renflexis. He wrote that the decline is “gradual” at 3% to 7% per quarter, but “you can absolutely see the strengthening trend.”

Now, biosimilars carry about a 25% discount to Remicade’s precompetition price, Gal wrote. But they’ll have to come down a little further before it makes sense for payers to make a wholesale switch to the copies, he added. Pfizer launched its biosimilar back in October 2016, and Merck followed in July 2017.

It hasn’t exactly been smooth sailing for the biosimilars since launch, despite upfront excitement from payers thinking they’d reap big savings by adopting the competitors. Pfizer’s Inflectra stalled for several quarters after launch, and that company sued J&J, arguing it had illegally protected Remicade’s sales through “anticompetitive” contracting.

J&J hit back, saying Pfizer wasn’t offering enough value to win business in the market. In August, a judge rejected J&J’s motion to dismiss and ruled that the lawsuit must proceed.

Inflectra’s sales so far this year amounted to $189 million in the U.S., compared with $2.82 billion for Remicade. Merck didn’t disclose Renflexis sales for the third quarter.

Even as Remicade faces biosim competition, J&J executives say they’re confident they can keep sales coming. As of the company’s third-quarter conference call, Remicade still claimed 93% of U.S. market share. The drug’s sales were down about 18% in the U.S. through the first nine months, which chief financial officer Joseph Wolk said was mostly “related to price.”

“We continue to compete there,” he said. “And we’re going to continue to do that. Because we know that that’s what patients and healthcare providers actually see as a product of most comfort. So, based on the safety and efficacy that we’ve demonstrated for a number of years and across all indications, we feel pretty strong that it still has a very strong place in the market.”

In October, the biosims got a boost in the form of a Medicare coverage decision from UnitedHealthcare. Thanks to a new rule from the Centers for Medicare and Medicaid Services, the insurance and PBM giant tagged the biosimilars as preferred for its Medicare Advantage plans over J&J’s brand.

https://www.fiercepharma.com/pharma/amid-biosim-competition-remicade-prices-gradually-slipping-analyst

Edwards says does not expect to pay $35M award in Boston Scientific case

Edwards Lifesciences (EW) commented a federal jury’s decisions in patent litigation between Edwards and Boston Scientific (BSX): “The jury awarded $35M in damages to Boston Scientific for infringement of U.S. patent number 8,992,608 (the ‘608 patent) for a transcatheter heart valve sealing skirt. Edwards does not expect to pay the jury award since, earlier this year, the U.S. Patent and Trademark office determined that all asserted claims of the ‘608 patent were invalid. The jury found that Edwards’ foundational U.S. Spenser Patents for transcatheter heart valves are valid, but not infringed by the Lotus devices. Edwards plans to appeal. Boston Scientific initiated litigation that now involves multiple patents in multiple venues, and will likely yield court actions over an extended period of time.”

https://thefly.com/landingPageNews.php?id=2835712