Cel-Sci aims to woo shareholders after CRO fight

• After Cel-Sci won an arbitration case against a CRO late last month, the biopharma appealed to its shareholders in a letter released Monday touting a promising future for its experimental immunotherapy in head and neck cancer.
• The dispute involved inVentiv (now know as SyneosHealth), which was contracted to carry out a Phase 3 trial for Cel-Sci’s Multikine. The CRO was found to have knowingly misled Cel-Sci, having promised to recruit 880 patients within 15 to 18 months. Instead, it recruited only 117 patients between 2011 and 2013.
• Cel-Sci hired a new CRO, and recruitment finally completed in September 2016 with an expanded patient total of 928. The company’s overall aim for 2018 is to get to the much-delayed readout of the Phase 3 trial for Multikine, which it hopes will confirm the drug’s efficacy.

Flush with success after winning a breach of contract arbitration with contract research organization inVentiv (now Syneos Health), Cel-Sci touted its future in the letter to shareholders, as well as emphasizing the damage done to Cel-Sci’s value by delays in the clinical trial.

According to Cel-Sci’s letter, investors that backed away during the arbitration process should come back.

“Now that the arbitration is resolved in our favor, this should no longer be an impediment to investors and should result in renewed investment interest in Cel-Sci,” said the letter.

The company is looking forward to the Multikine Phase 3 data, believing that it will have a significant impact on its market cap.

Cel-Sci boldly predicted that the compound, given Food and Drug Administration approval, would become part of the standard of care to be used in first-line head and neck cancer.

“Cel-Sci is a cancer immunotherapy company… In the past 18 months, several successful Phase 3 cancer immunotherapy companies were sold for $7 billion to almost $12 billion. They had positive survival data from their pivotal studies, but had not yet received FDA approval. Recently, one cancer immunotherapy company with not yet completed Phase 3 studies was sold for about $1.6 billion. Should the Cel-Sci Phase 3 study be successful, the potential market for our drug will be substantially larger than the markets of the multi-billion dollar companies mentioned above,” said the letter.

The prospects for Multikine might not be as rosy as the company purports. The delays to clinical trials were only in part due to the actions of the CRO — Multikine has been in development for the better part of a decade. The drug was placed on partial clinical hold for about a year. The future for Multikine is anything but certain; although that’s not how Cel-Sci is selling it.

https://bit.ly/2maHu9I

Dova downgraded as high price tag threatens to slow new drug’s pickup

• Investment bank Leerink lowered its rating for Dova Pharmaceuticals stock from “Outperform” to “Market Perform,” reflecting what analysts expect to be a slow launch of the biotech’s new drug because of its higher-than-expected price.
• The drug, Doptelet, received regulatory approval in late May as a treatment for adults with chronic liver disease who have low platelet counts and upcoming medical procedures that could cause increased bleeding. Dova is also looking to get Doptelet cleared for immune thrombocytopenic purpura (ITP), but in the meantime strapped it with a $9,000 to $13,500 price tag for a five-day regimen, depending on the dose.
• “This new rating reflects our views of the complex commercial environment for Doptelet in its first indication, and the uncertainty about the regulatory outlook for the ITP application,” Leerink analyst Geoffrey Porges wrote in a July 9 investor note.

Pfizer pulled a rare move this week when, following talks between CEO Ian Reid and President Donald Trump, it agreed to rescind a swath of newly enacted price hikes. The decision was surely seen as a win by the administration — which has, through the Department of Health and Human Services, reportedly been pushing drugmakers to slash prices — yet it’s not particularly reflective of wider pharmaceutical sentiment regarding price.

Despite intense pushback from payers and lawmakers, many drug manufacturers don’t look poised to enact meaningful price cuts anytime soon. The nation’s 10 largest companies suggested as much in response letters to Sens. Elizabeth Warren, D-Mass., and Tina Smith, D-Minn., last month.

Lofty price tags aren’t solely tied to big pharma either. Dova, for instance, raised eyebrows when it revealed a $9,000 wholesale acquisition cost for a five-day course of 40 mg Doptelet. Analysts noted the price is not only higher than the average platelet transfusion, but in many cases would be more expensive than whatever medical procedure patients were about to undergo.

And that could be a big problem for the drug’s uptake.

“Even for the patients that are most suitable for Doptelet, the patient identification, verification and approval processes mean many will not actually receive the treatment despite theoretically being eligible,” Leerink’s Porges wrote in the July 9 note.

Talking to proceduralists and liver specialists, Leerink also found many factors stand in the way of physicians adopting Doptelet treatment, such as scheduling logistics, reimbursement and cost.

“All these issues can be solved, but it seems likely that it will take many quarters before the provider and patient logistics are streamlined such that significant recurring treatment volume can be expected,” Porges wrote. Along with its rating downgrade, Leerink now expects $9 million in Doptelet sales in 2018 versus consensus of $13 million, and $347 million of sales in 2022 versus consensus of $343 million.

Dova, meanwhile, estimates a roughly $2.5 billion opportunity for its debut drug, comprised of about $800 million for the first indication and $1.7 billion for follow-on acute indications.

At investment bank Jefferies’ 2018 Healthcare Conference, Dova also laid out its early launch plans. Sales representatives began reaching out to mostly hepatologists, as well as some interventional radiologists, in early June.

Company leadership acknowledged too they didn’t intend to offer rebates at launch for the first indication, and didn’t think payers would be “actively managing the category,” according to a June 5 investor note from Jefferies analyst Eun Yang.

https://bit.ly/2JjEUar

New ways to conquer sleep apnea compete for place in bedroom

Every night without fail, Paul Blumstein straps on a mask that prevents him from repeatedly waking up, gasping for air.

It’s been his routine since he was diagnosed with a condition called sleep apnea. While it helps, he doesn’t like wearing the mask.

“It’s like an octopus has clung to my face,” said Blumstein, 70, of Annandale, Virginia. “I just want to sleep once in a while without that feeling.”

It’s been two decades since doctors fully recognized that breathing that stops and starts during sleep is tied to a host of health issues, even early death, but there still isn’t a treatment that most people find easy to use.

Airway pressure masks, the most common remedy, have improved in design, getting smaller and quieter, but patients still complain about sore nostrils, dry mouths and claustrophobia.

Now, new ways of conquering sleep apnea, and the explosive snoring that comes with it, are vying for a place in the bedrooms of millions of people craving a good night’s sleep. Products range from a $350 restraint meant to discourage back sleeping to a $24,000 surgical implant that pushes the tongue forward with each breath.

It’s been two decades since doctors fully recognized that interrupted breathing during sleep is tied to a host of health issues, but there still isn’t a treatment for sleep apnea that most people find easy to use.

Mouthpieces, fitted by dentists, work for some people but have their own problems, including jaw pain. Some patients try surgery, but it often doesn’t work. Doctors recommend weight loss, but diet and exercise can be challenging for people who aren’t sleeping well.

So far, no pills for sleep apnea exist, but researchers are working on it. One drug containing THC, the active ingredient in marijuana, showed promise in a study this year.

What is sleep apnea? In people with the condition, throat and tongue muscles relax and block the airway during sleep, caused by obesity, aging or facial structure. They stop breathing, sometimes for up to a minute and hundreds of times each night, then awake with loud gasping and snoring. That prevents them from getting deep, restorative sleep.

They are more likely than others to have strokes, heart attacks and heart rhythm problems, and they’re more likely to die prematurely. But it’s hard to tease out whether those problems are caused by sleep apnea itself, or by excess weight, lack of exercise or something else entirely.

For specialists, the first-choice, most-studied remedy remains continuous positive airway pressure, or CPAP. It’s a motorized device that pumps air through a mask to open a sleeper’s airway. About 5 million Americans have tried CPAP, but up to a third gave up during the first several years because of discomfort and inconvenience.

Martin Braun, 76, of New York City stopped using his noisy machine and awkward mask, but now he’s trying again after a car crash when he fell asleep at the wheel. “That’s when I realized, OK this is serious stuff already,” said Braun, who has ordered a quieter CPAP model.

Sleep medicine is a relatively new field. The most rigorous studies are small or don’t follow patients for longer than six months, said Dr. Alex Krist of Virginia Commonwealth University, who served on a federal guidelines panel that reviewed sleep apnea treatments before recommending against screening adults who have no symptoms.

“We don’t know as much about the benefits of treating sleep apnea as we should,” said Krist, vice-chair of the U.S. Preventive Services Task Force.

While scientists haven’t proved CPAP helps people live longer, evidence shows it can reduce blood pressure, improve daytime sleepiness, lessen snoring and reduce the number of times a patient stops breathing. CPAP also improves quality of life, mood and productivity.

With noticeable results, many CPAP users, even those like Blumstein with a love-hate relationship with their devices, persist.

Blumstein was diagnosed about 15 years ago after he fell asleep behind the wheel at a traffic light. He shared his frustrations with using a mask at a recent patient-organized meeting with the Food and Drug Administration, as did Joelle Dobrow of Los Angeles, who said it took her seven years to find one she liked.

“I went through 26 different mask styles,” she said. “I kept a spreadsheet so I wouldn’t duplicate it.”

Researchers are now focused on how to get people to use a mask more faithfully and predicting who is likely to abandon it and could start instead with a dental device.

“It’s the bane of my existence as a sleep doctor,” said Dr. James Rowley of Wayne State University in Detroit. “A lot of what sleep doctors do in the first few months after diagnosis is help people be able to use their CPAP.”

Getting it right quickly is important because of insurers’ use-it-or-lose-it policies.

Medicare and other insurers stop paying for a rented CPAP machine if a new patient isn’t using it enough. But patients often have trouble with settings and masks, with little help from equipment suppliers, according to Dr. Susan Redline of Brigham and Women’s Hospital in Boston.

All told, it can drive people toward surgery.

Victoria McCullough, 69, of Escondido, California, was one of the first to receive a pacemaker-like device that stimulates a nerve to push the tongue forward during sleep. Now, more than 3,000 people worldwide have received the Inspire implant. Infections and punctured lungs have been reported; the company says serious complications are rare.

McCullough said she asked her doctor to remove the device soon after it was activated in 2015.

“It was Frankenstein-ish. I didn’t like it at all,” McCullough said. “My tongue was just thrashing over my teeth.”

Others like the implant. “My quality of life is 100 percent better,” said Kyleene Perry, 74, of Edmonds, Washington, who got one in February after struggling with CPAP for two years. “People are saying, ‘You look so much better.’ I have a lot more energy.”

The THC pill, known as dronabinol, already is used to ease chemotherapy side effects. A small experiment in 73 people suggests it helps some but wasn’t completely effective. It may work better in combination with CPAP or other devices, said researcher David Carley of the University of Illinois at Chicago. He owns stock in Respire Rx Pharmaceuticals, which has a licensing agreement with the university for a sleep apnea pill.

As the search for better treatments continues, listening to patients will be key, said Redline.

“We are actually just treating a very tiny percentage of people effectively,” she said.

https://bit.ly/2LggOPB

Immune-based therapy may help when melanoma spreads to brain

 A type of therapy that harnesses the immune system is giving new hope to people battling a once hopeless cancer — melanoma that’s spread to the brain.

New research involving more than 2,700 U.S. patients is confirming what specialists in the field have long known — that “checkpoint blockade” treatment can beat back these devastating tumors.

“Physicians who treat patients with melanoma brain metastases have seen first-hand the dramatic improvements in survival that immunotherapy can achieve,” said one such specialist, Dr. Jason Ellis.

“This study provides data to support our individual clinical observations,” said Ellis, a neurosurgeon at Lenox Hill Hospital in New York City. He wasn’t involved in the new study.

Checkpoint blockade agents are not chemotherapy — instead of acting directly on tumor cells, they manipulate the patient’s immune system so that it targets and destroys the melanoma cells.

This type of “immunotherapy” was approved by the U.S. Food and Drug Administration in 2011.

The new research was led by Dr. J. Bryan Iorgulescu, a postdoctoral fellow in pathology at Brigham and Women’s Hospital/Harvard Medical School in Boston. His team explained that about one in every 54 Americans will develop a melanoma skin cancer in their lifetime.

Luckily, most cases are detected early and easily cured via surgery. But sometimes the tumor has had time to spread, even to the brain. In fact, advanced melanomas are now the third-leading cause of metastatic brain cancer, the research team noted.

In its analysis, Iorgulescu’s group tracked outcomes from 2,753 patients with melanoma that had spread to the brain. The patients were treated at cancer centers nationwide between 2010 and 2015.

The study found that first-line treatment with checkpoint blockade immunotherapy was associated with a rise in median overall survival from 5.2 months to 12.4 months.

Treatment was also tied to an increase in the four-year overall survival rate: Just over 28 percent of patients who got the immunotherapy survived at least four years, compared to about 11 percent who didn’t get the therapy, the findings showed.

The researchers noted that survival benefits were even greater for those patients whose melanoma had not already spread beyond the brain, to organs such as the liver or lungs.

“Our findings build on the revolutionary success of checkpoint blockade immunotherapy clinical trials for advanced melanoma, and demonstrate that their substantial survival benefits also extend to melanoma patients with brain metastases,” Iorgulescu said in a Brigham and Women’s news release.

Dr. Michael Schulder helps direct neurosurgery at Long Island Jewish Medical Center in New Hyde Park, N.Y. He wasn’t involved in the new analysis, but agreed it confirms what many cancer specialists have long known, “namely, that the use of checkpoint inhibitors has revolutionized the treatment and outlook for patients with metastatic melanoma.”

The Boston researchers did offer one caveat, however: Not every patient has equal access to this expensive treatment. Insurance status was a real barrier to immunotherapy for some patients with these advanced tumors, and uninsured patients were much less likely to get the treatment compared to people with private insurance or those on Medicare.

The findings were published July 12 in Cancer Immunology Research.

More information

The U.S. National Cancer Institute has more on melanoma.

SOURCES: Jason Ellis, M.D., neurosurgeon, Lenox Hill Hospital, New York City; Michael Schulder, M.D., vice chair, neurosurgery, North Shore University Hospital, Manhasset, N.Y., and Long Island Jewish Medical Center, New Hyde Park, N.Y.; Brigham and Women’s Hospital, news release, July 12, 2018

https://bit.ly/2mb9ZE7

Half of Americans trying to lose weight

In a country where four out of 10 adults are obese, it’s probably good news that half of U.S. adults say they’ve recently tried to shed some pounds.

They did this most often through exercise, cutting calories and eating their fruits and veggies, according to a new government survey that tracked Americans’ weight-loss attempts between 2013 and 2016.

Overall, 49 percent of respondents said they’d tried to lose weight in the past year — including two-thirds of those who were obese.

As of 2016, almost 40 percent of American adults were obese, according to researchers with the U.S. Centers for Disease Control and Prevention’s National Center for Health Statistics (NCHS).

So it’s important to know how many Americans are trying to lose weight — and how they’re doing it, said Kirsten Herrick, a senior research fellow with the NCHS who worked on the study.

There were some positive signs, said a registered dietitian who wasn’t involved in the research.

The most common weight-loss methods were exercise and eating less — each reported by 63 percent of people aiming to shed pounds. And half said they were eating more fruits, vegetables and salads.

“The good news is that people seem to recognize that weight loss is about changing habits, not quick-fix diets,” said Connie Diekman, director of university nutrition at Washington University in St. Louis.

Sustainable diet changes are critical, Diekman said. That includes cutting sugary, fat-laden junk food, and replacing it with plenty of fruits, vegetables, fiber-rich grains and other healthful whole foods.

Regular exercise can improve your overall health, and may aid in weight loss, Diekman noted. But, she said, people need to make lasting changes in how they eat, rather than try fad diets.

The report was based on a nationally representative sample of Americans aged 20 and older. Many people said they’d tried to lose weight in the past year, though the figures varied among different groups.

Women were more likely than men to have aimed for weight loss (56 percent versus 42 percent), the findings showed.

Income made a difference as well, with wealthier men and women significantly more likely to say they tried to slim down.

It’s possible, Herrick said, that the disparity could reflect the barriers low-income Americans can face when it comes to losing weight — like having the time and place to exercise, or being able to afford healthy food.

But, she added, it’s impossible to know from this survey.

Besides turning to exercise and veggies, survey respondents also commonly said they’d cut down on junk food and fast food, and tried to limit sugar. Many said they “drank a lot of water.” The vast majority of people who tried to lose weight said they’d used at least two tactics.

What’s not clear is how often those efforts paid off.

Diekman pointed out that the “report provides a glimpse of what Americans are doing to achieve a healthy weight, but what it does not show is how individuals are doing.”

Since most Americans are overweight or obese, she added, doctors and other health providers should be asking people about how they view their weight and their health.

If you need help managing your weight, Diekman suggested talking to your doctor, who may refer you to a dietitian.

Having a plan that is “practical, achievable and maintainable” is key, she said.

The report was published July 12 in the CDC’s NCHS Data Brief.

More information

The U.S. National Heart, Lung, and Blood Institute has advice on achieving a healthy weight.

SOURCES: Kirsten Herrick, Ph.D., M.Sc., senior research fellow, National Center for Health Statistics (NCHS), U.S. Centers for Disease Control and Prevention; Connie Diekman, M.Ed., R.D., director, university nutrition, Washington University in St. Louis; July 12, 2018, NCHS Data Brief

https://bit.ly/2uojCUL

Probing the part of the brain where autism may begin

 The underpinnings of autism may lie in an unexpected part of the brain, a small study suggests.

Scientists conducted brain scans on 20 boys with autism and 18 boys without the neurodevelopmental disorder. The scans showed that boys with autism had a significantly flatter surface on the right side of their cerebellum. That side happens to be involved in language processing.

The researchers also found that a flatter cerebellum was associated with differences in thinking abilities and communication, two skills often affected by autism.

But the study did not prove that differences in the cerebellum caused autism.

Still, “Our findings suggest we may need to rethink the role of cerebellar function and structure in young individuals at risk for atypical brain development,” said senior study author Kristina Denisova. She’s an assistant professor of clinical neurobiology at Columbia University in New York City.

While the cerebellum is only 10 percent of the brain’s total volume, it contains 80 percent of all neurons (brain cells), the researchers explained. It had been believed that this area governed motor function for the most part, but recent research has hinted that it might also regulate implicit learning, sensory development and thinking skills.

Yet, most brain scan studies on autism have focused on the cerebrum, which is larger than the cerebellum despite having fewer neurons, the researchers said.

“That’s partly a function of the unique, irregular shape of the cerebellum, which is difficult to analyze with conventional imaging techniques,” Denisova explained in a Columbia news release.

“Imagine looking at only 20 percent of the brain’s neurons and attempting to paint a comprehensive picture of atypical development in humans based on such limited knowledge,” she said.

Denisova added that “one interpretation of the findings is that increased structural complexity of the cerebellum may enhance implicit learning in atypically developing boys.”

That question is now being investigated by the researchers in infants and toddlers who are at risk for developing autism later in life, the researchers said.

The findings were published online July 11 in the journal PLOS One.

More information

The Autism Society has more on autism.

SOURCE: Columbia University Irving Medical Center, news release, July 11, 2018

https://bit.ly/2zvjCXT

Abbott Gets FDA OK for Next-Gen Device to Treat Leaky Heart Valves

Abbott  (NYSE: ABT) today announced it received approval from the U.S. Food and Drug Administration (FDA) for a next-generation version of its leading MitraClip®heart valve repair device used to repair a leaky mitral valve without open-heart surgery. The transcatheter clip-based therapy, now on a third generation of product innovations, has been used to treat more than 65,000 patients worldwide over the last ten years. The next-generation MitraClip system provides cardiologists with advanced steering, navigation, and positioning capabilities for the clip, making it easier to use in difficult anatomies. The enhanced system is designed to allow for more precise placement during deployment, resulting in more predictable procedures, and additionally offers a second clip size with longer arms that expands the reach of the clip-based device.The additional clip size is designed to help doctors treat patients who have morecomplex anatomies when repairing the mitral valve. Abbott received CE Mark for the next-generation device earlier this year, allowing for sale of the devices in the European Union and other countries that recognize this regulatory designation. “Physicians rely on MitraClip as an alternative to surgery for patients who aren’t surgical candidates and may need treatment to relieve their symptoms or to survive,” said Francesco Maisano, M.D., Prof., UniversitätsSpital Zürich, Switzerland, who was an early implanter of MitraClip. “The enhanced MitraClip design allows for even more precise navigation, accuracy, and stability during valve repairs, which may be important when treating people with more complex or advanced valve disease.” A leaking mitral valve, known as mitral regurgitation (MR) is a serious, progressive heart disease in which the flaps of the mitral valve do not close properly, allowing blood to flow backward into the heart. Incidence of mitral regurgitation increases with age, with nearly one in 10 people over the age of 75 having moderate to severe disease1. Before MitraClip, people who were not eligible for the standard-of-care surgery to treat their MR could only manage their symptoms with medications that don’t stop the progression of the disease. Left untreated, MR leads to a variety of life-altering symptoms and severe complications, and may ultimately lead to heart failure and death.1,2,3. “Abbott engineers designed these enhancements based on feedback from doctors to improve device delivery and to treat more types of cases and anatomies,” said Michael Dale, vice president for Abbott’s structural heart business. “We’re committed to helping people with mitral regurgitation return to living their best lives, and these advances will enable doctors to treat even more patients without surgery.” MitraClip treats people with degenerative mitral regurgitation and is a therapy that is delivered via a catheter to the heart through a blood vessel in the leg. MR patients are often not eligible for the standard-of-care surgery because of advanced age, frailty, multiple comorbidities or other complicating factors and the therapy offers a minimally invasive alternative. Treatment with MitraClip provides almost immediate symptom relief and patients are released from the hospital on average after two days. Abbott recently began enrollment in the MitraClip EXPAND clinical study, a prospective study evaluating the safety and performance of the new MitraClip system in a contemporary real-world setting. Saibal Kar, M.D., director of Interventional Cardiac Research at the Smidt Heart Institute at Cedars-Sinai in Los Angeles, Calif., treated the first patient enrolled, and is the lead investigator of the study. EXPAND will enroll approximately 1,000 patients in more than 50 centers across the U.S. and Europe and interim results from the study are expected later this year. https://bit.ly/2mdePRd