Celgene adds $65M discovery alliance with Evotec to spur new cancer drugs

Celgene has added a $65 million upfront portion of oncology discovery work with Evotec, 18 months after the two companies allied on neurodegeneration work.

As is typically the case with Celgene $CELG and Evotec, there aren’t an awful lot of details to work with. There’s no mention about milestones in the two-paragraph release, other than a reference to “significant” biobucks. Given the size of the upfront, though, those back-ended milestones are likely to run into the hundreds of millions of dollars.

Cancer R&D is the biggest leg of the R&D table at Celgene, which has been looking to expand beyond Revlimid with new therapies in the oncology field. Beyond its marketed cancer drugs, which includes Pomalyst and Thalomid, Celgene has the BCMA CAR-T bb2121 in the pivotal part of the pipeline, racing with the competition to stay in the lead on that score.

There’s also a major emphasis on inflammation and immunology as researchers scramble to get ozanimod back in front of regulators.

Celgene has been spending big bucks on its pipeline for years. But new CEO Mark Alles is expected to get some new revenue rolling in, so it won’t be dependent on big annual price hikes on Revlimid, which has attracted some unfavorable attention from the Trump administration.

Evotec, of course, won’t be offering any immediate help on that score. But it has another big notch to add to a belt crowded with discovery alliances like these.

https://bit.ly/2KJPOr4

Tesla Model 3 fails to get Consumer Reports nod due to 'big flaws'

Influential U.S. magazine Consumer Reports will not recommend Tesla Inc's Model 3 sedan, saying on Monday it braked slower than a full-sized pickup truck, taking the shine off a day of gains for shares in Elon Musk's electric car company.

Musk had driven shares in Tesla as much as 4 percent higher with weekend tweets showing the Silicon Valley company was aiming initially to deliver higher-priced, more profitable fully-loaded editions of the Model 3.
The car is seen as crucial to Tesla's profitability at a time when it is battling to reverse production shortfalls, confronting reports of crashes involving its vehicles and facing increased skepticism over its finances.
On Twitter, Musk said the fully-loaded Model 3, with all-wheel drive, a dual motor and a 310-mile (499-km) range - but excluding its vaunted Autopilot feature - would cost $78,000. The company has not yet begun to make the $35,000 base price version that Tesla originally claimed would make it a mass-market vehicle.
Consumer Reports, however, declined to recommend the Model 3 and criticized it for having overly long stopping distances and a difficult-to-use center touchscreen.
The magazine, which provides an annual rating of vehicles sold in the United States, said even though its tests found plenty to like about the Model 3 and it was a thrill to drive, it had "big flaws."
Tesla's stopping distance of 152 feet (46 m) when braking at 60 miles per hour (100 km per hour) was "far worse" than any contemporary car tested by the magazine and about seven feet longer than the stopping distance of a Ford F-150 full-sized pickup, it said.
Tesla said its own testing had found braking distances of 133 feet on average using the 18" Michelin all season tire, and as low as 126 feet with all tires currently available.
"Unlike other vehicles, Tesla is uniquely positioned to address more corner cases over time through over-the-air software updates, and it continually does so to improve factors such as stopping distance," Tesla said.
"LOSE MONEY AND DIE"
Research firm Berenberg also helped give Tesla shares a boost on Monday, after it raised its share price target to $500 from $470 on Friday.
Its forecast, the highest among over two dozen analysts tracked by Thomson Reuters, is now more than $200 above the stock's price, which has fallen $100 from September's peak.
Musk, whose refusal to answer analysts' questions on a call this month also hurt company shares, said in his weekend tweets that Tesla had to focus first on delivering Model 3s that were priced higher than the base version, or it would "die".
"With production, 1st you need achieve target rate & then smooth out flow to achieve target cost. Shipping min cost Model 3 right away wd cause Tesla to lose money & die. Need 3 to 6 months after 5k/wk to ship $35k Tesla & live," Musk tweeted.
The new Model 3 version's price was similar to the BMW M3, "but 15 percent quicker & with better handling," Musk added, without giving details.
Also over the weekend, a Model S sedan crashed and killed the driver in the San Francisco Bay Area, one of a recent spate of crashes, some of which involved fire and some of which took place while the company's semi-autonomous Autopilot technology was engaged.
In the latest case, the car launched off a rural county road into a nearby pond more than 60 feet from the road, state and local law enforcement said.
The car appeared to be going faster than the posted 35 mph limit, but authorities had not yet determined its speed and whether Autopilot was engaged, a California Highway Patrol spokesman said.
Tesla said it did not yet know the facts and had not yet received data from the car, but was cooperating with local authorities.
The National Highway Traffic Safety Administration said it was gathering information and would "take action as appropriate."
On Friday, proxy adviser Institutional Shareholder Services (ISS) backed a shareholder proposal to separate Musk's current chairman and CEO roles, suggesting that shareholders would be better served by having Musk focus on running the company.
https://bit.ly/2s04LxC

Link between IBD and Parkinson’s might allow doctors to slow down condition

Doctors may be able to modify or slow down the progress of the neurological condition Parkinson’s disease in the future by spotting signs of it in patients with inflammatory bowel disease (IBD), suggest a study published in the journal Gut.

Danish researchers found patients with IBD appeared to have a 22% greater risk of developing Parkinson’s disease in a study that monitored participants for almost 40 years.

IBD, Crohn’s disease and ulcerative colitis are chronic conditions with onset in young adulthood.

It has already been suggested in previous studies that inflammation plays a role in the development of Parkinson’s disease and multiple system atrophy.

Enteric inflammation—the main symptom of inflammatory bowel disease—can occur in patients with Parkinson’s disease and may reflect the earliest manifestations of the neurological condition’s development.

Experts have suspected for some time that there may be a ‘gut-brain axis’ where the intestinal environment influences the functioning of the central nervous system and intestinal imbalance may precede and cause Parkinson’s disease.

Therefore, a team of Danish researchers led by Dr. Tomasz Brudek of the Research Laboratory for Stereology and Neuroscience, Bispebjerg and Frederiksberg Hospital, Copenhagen, set out to examine whether IBD was associated with risk of Parkinson’s disease and multiple system atrophy.

They carried out a nationwide population-based cohort study involving all individuals diagnosed with IBD in Denmark between 1977 and 2014—76,477 people—and more than 7.5 million non-IBD individuals from the general population, who were comparable in terms of gender, age and vital status.

All participants were followed from IBD diagnosis/index date to the occurrence of Parkinson’s disease and multiple system atrophy, using data from the Danish National Patient Register.

During the 37-year study period, 335 patients with IBD (0.4%) and 39,784 non-IBD individuals (0.5%) were diagnosed with Parkinson’s disease, whereas 13 patients with IBD (0.02%) and 866 non-IBD individuals (0.01%) were diagnosed with multiple system atrophy.

Analysis of the results showed that patients with IBD had a 22% higher risk of Parkinson’s disease compared with non-IBD individuals.

This increased risk was present independent of age at IBD diagnosis, gender or length of follow-up.

The overall incidence of multiple system atrophy was low in the study, but analysis suggested a tendency towards higher risk (41% higher) of developing multiple system atrophy in patients with IBD compared with non-IBD individuals. The estimates were similar for women and men.

There was a 35% greater risk of parkinsonism among patients with ulcerative colitis but not a significantly higher risk among patients with Crohn’s disease.

This was an observational study, so no firm conclusions can be drawn about cause and effect, but the authors said they believed their work was the first epidemiological study investigating the risk of parkinsonism in an unselected, nationwide cohort of patients with IBD with long-term follow-up—patients were followed for more than 8 million person-years.

The authors concluded: “The study suggests that clinicians should be aware of symptoms of parkinsonism in patients with IBD, and the study demonstrates the need for further investigation into the role of intestinal inflammation and brain gut-microbiome axis in the aetiology of parkinsonism.

“The identification of risk factors associated with prodromal phases of Parkinson’s disease may allow for early intervention studies that could modify or slow down disease progress.”

More information: Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977-2014, Gut, gut.bmj.com/lookup/doi/10.1136/gutjnl-2017-315666

https://bit.ly/2rYv5c6

Avoiding car for travel could significantly lower risk of illness and death

People who are more active when commuting to work by walking or cycling could be cutting their relative risk of developing ischaemic heart disease or stroke by 11% and their relative risk of dying from these diseases by 30%, suggests a study published in the journal Heart.

Physical activity, including less vigorous forms such as walking and cycling, reduces

the risk of cardiovascular disease, but despite this well-known benefit, levels of activity are still low in many countries.

There are concerns that many peoples’ lives involve increasingly sedentary occupations and little opportunity for leisure time physical activity. Thus, activity as part of a journey—such as the commute or for transport in general—can offer a comparatively easy way to integrate exercise into daily life.

Despite current clinical practice guidelines recommending physical activity, the benefits of active travel on mortality and morbidity are still unclear.

Therefore, a team of researchers from the University of Cambridge, London School of Hygiene & Tropical Medicine, and Imperial College London, set out to investigate the associations between using alternatives to the car which are more active for commuting and non-commuting purposes, and illness and mortality.

They used data on 358,799 participants in the UK Biobank, a national population based study designed to measure and track the health of adult residents of primarily urban areas in the UK.

Data was studied on these people between 2006 and 2010. People were followed up for an average of seven years. They were asked about their commute and non-commute travel and to detail whether they relied exclusively on the car or used alternative modes of transport that were more active at least some of the time.

Outcome measures used were incident and fatal cardiovascular disease (CVD), incident and fatal cancer, and all-cause mortality.

Approximately two-thirds of commuters relied exclusively on the car to travel to work, with more active travel patterns being more frequently reported for non-commuting travel.

Cycling was less prevalent, being mentioned by 8.5% and 7% of regular commuters for commuting and non-commuting travel, respectively, and by 4.8% of other participants.

Analysis of the data showed that regular commuters with more active patterns of travel on the commute had a 11% lower risk of incident cardiovascular disease (CVD) and 30% lower risk of fatal CVD.

Those regular commuters who also had more active patterns of commute and non-commute travel combined had an even lower risk of fatal CVD—43% less risk.

Among people who were not regular commuters, more active patterns of travel were associated with an 8% lower risk of all-cause mortality.

This was an observational study, so no firm conclusions can be drawn about cause and effect, but the authors said their analysis had used a very large multicentre general population dataset, and had focused on feasible travel choices for commuting and non-commuting travel.

The authors took into account potential confounding factors, such as other physical activity, fruit and vegetable consumption and measures of socioeconomic status.

They also excluded participants who developed disease or died within two years of follow-up to reduce the likelihood of “reverse causation”, meaning that those who have early signs of disease may be less active because of their illness and so more likely to travel by car.

They concluded that interventions that encourage people to make more use of public transport, walking and cycling could be more widely promoted, including by clinicians.

“More active patterns of travel were associated with a reduced risk of incident and fatal CVD and all-cause mortality in adults. This is an important message for clinicians advising people about how to be physically active and reduce their risk of disease,” they said.

In an accompanying editorial, Dr. April Mohanty of the VA Salt Lake City Health Care System in the USA, said: “This study provides further evidence to support efforts, including policies and guideline recommendations, that encourage active traveleven if that is only possible for part of the journey.”

More information: Using alternatives to the car and risk of all-cause, cardiovascular and cancer mortality, Heart (2018). heart.bmj.com/lookup/doi/10.11 … heartjnl-2017-312699

https://bit.ly/2KJaYG5

Lannett gets FDA OK for cancer side effects med generic

Lannett Company, Inc. (NYSE: LCI) today announced that it received approval from the U.S. Food and Drug Administration (FDA) of its Abbreviated New Drug Application (ANDA) for Dronabinol Capsules USP, 2.5 mg, 5 mg and 10 mg, the therapeutic equivalent to the reference listed drug, Marinol^® Capsules 2.5 mg, 5 mg and 10 mg of AbbVie Inc. For the 12 months ended March 2018, total U.S. sales of Dronabinol Capsules USP, 2.5 mg, 5 mg and 10 mg, was approximately $120 million, according to IMS.

“The approval of Dronabinol Capsules adds to our sizeable portfolio of near-term product opportunities,” said Tim Crew, chief executive officer of Lannett. “We expect to commence marketing several products including Dronabinol Capsules over the course of this year. Currently, only a handful of manufacturers supply generic Dronabinol Capsules to the U.S. market.”

https://bit.ly/2GDPhVo

China considers scrapping birth limits by 2019

China is considering ending the limits it sets on the number of children a family can have, Bloomberg reported on Monday, citing people familiar with the matter.

China’s population is aging rapidly, with the number of births falling by 3.5 percent to 17.23 million last year despite the country’s decision in late 2015 to relax the controversial “one-child” policy and allow couples to have a second child.

The State Council, or cabinet, has commissioned research on ending the country’s birth limits on a nationwide basis, the Bloomberg report said.

A decision could be made in the last quarter of this year or in 2019, the report said.

China implemented its one-child policy in the 1970s to limit population growth, but authorities are concerned that a dwindling workforce will not be able to support an increasingly aging population.

The one-child policy also contributed to a sharp gender imbalance, with 32.66 million more males than females at the end of 2017.

https://reut.rs/2rX0VoW

More U.S. kids overdosing on ADHD drugs

The surge in U.S. kids taking medication for attention-deficit hyperactivity disorder (ADHD) is having an unintended side effect, a new study suggests: more children and teens are overdosing on these drugs.

Nationwide, U.S. Poison Control Centers received more than 156,000 calls about exposures to ADHD drugs among youth 19 years old and younger between 2000 and 2014, averaging 200 calls a week and 29 calls a day, researchers report in Pediatrics.

“While the number of calls about ADHD medication exposures among children and adolescents fluctuated throughout the years of the study, there was an overall increase of 61 percent during the study period,” said senior study author Dr. Gary Smith, director of the Center for Injury Research and Policy at Nationwide Children’s Hospital in Columbus, Ohio.

“The increase in calls coincided with an increase in ADHD diagnoses and medication prescriptions during the same time period nationally and regionally,” Smith said by email.

Roughly three-fourths of the calls were about kids aged 12 and younger, the study found. Kids under 6 years old typically got into medications that were not stored properly, while older children usually took the wrong amount of their prescribed ADHD drugs.

While teens accounted for a smaller proportion of overdose calls, about half of these exposures were intentional abuse, misuse or suicide attempts.

“As a result, the exposures in this age group were more likely to lead to serious outcomes than those among younger children,” Smith said.

Medication errors related to dosing or timing were the most common cause of overdoses, accounting for 42 percent of calls, the study found.

Two medications were involved in the majority of cases: methylphenidate (Ritalin, Concerta) and amphetamine (Adderall, Dexedrine).

Most cases were not serious: 60 percent didn’t require kids to see a doctor or go to the hospital.

However, about 6 percent of cases required hospital admission, and children died in three cases.

One limitation of the study is that calls to Poison Control may not necessarily capture every case of accidental or intentional overdose.

More than 1 in 10 U.S. kids are diagnosed with ADHD, which is characterized by social and behavioral problems as well as challenges in school like difficulty with focusing or sitting still. Stimulant medications can help with some behavior and attention issues.

When taken as directed, stimulants may have mild side effects like jitteriness that typically wear off when kids stop taking these medications, Dr. William Pelham, Jr., director of the Center for Children and Families at Florida International University in Miami, said by email. He wasn’t involved in the study.

But the drugs can be more dangerous for children who don’t have ADHD or who take too much medicine, said Dr. Benjamin Shain of NorthShore University HealthSystem and the University of Chicago Pritzker School of Medicine.

“Adverse effects of taking too much stimulant medication include fast heart rate, increased blood pressure, tremors, and agitation,” Shain, who wasn’t involved in the study, said by email.

“Worse case scenarios include schizophrenic-like psychosis, heart attack, stroke, seizures and death,” Shain added. “Adverse effects are the same whether the person has ADHD or not.”

Parents can help prevent accidental overdoses in young children by storing pills out of reach and supervising daily doses for kids who need the drugs so they don’t take it more often than they should, said Dr. Yolanda Evans of Seattle Children’s Hospital.

“Things that can help include weekly pill boxes to show kids that they’ve already taken their dose for the day, parent help in distributing daily doses of medications, or (if possible) having a school nurse give the morning dose of a medication at school,” Evans, who wasn’t involved in the study, said by email.

With older kids and teens, supervision is still key to avoid accidental or intentional misuse of ADHD drugs, Evans said. Even when kids are old enough to take pills on their own, parents should provide the daily doses needed instead of giving kids the bottle of pills to manage on their own.

SOURCE: bit.ly/2IzBhlf Pediatrics, online May 21, 2018.

https://reut.rs/2IB6VyH