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Wednesday, May 30, 2018

After ASCO preview flop, Syndax bets on new combo deal with Nektar

San Fran’s I/O darling Nektar Therapeutics $NKTR is handing off access to its popular cancer candidate NKTR-214 to see how the therapy fairs when paired with Syndax’s struggling drug entinostat.

The duo inked a collaboration and licensing deal that gives Syndax $SNDX the right to run a combo study testing the drugs against metastatic melanoma in patients who have previously progressed when on an anti-PD-1.
The hope is that entinostat, Syndax’s oral, small molecule Class 1 specific HDAC inhibitor, could be put to good use alongside NKTR-214, the CD122-biased agonist that was the impetus behind Bristol-Myers’ $3.6 billion deal with Nektar back in February.
“Previous Phase II data with entinostat and high dose IL-2 in renal cell cancer and our promising preclinical data generated with NKTR-214, laid the scientific and clinical foundation for this collaboration,” said Briggs Morrison, CEO at Syndax, in a statement. “Working with Nektar allows us to increase the potential impact entinostat may have in the treatment of PD-1 refractory metastatic melanoma patients, and complements the exciting data we have seen when combining entinostat with Keytruda in a similar population.”
By “exciting data,” Morrison is referring to the clinical trial info shared earlier this month with its ASCO abstracts — the news that sent Syndax’s stock plummeting 23%. That’s because the company’s lead drug, entinostat, largely flopped a mid-stage combo trial testing the drug with Keytruda. The combo produced an objective response rate of only 11% in pre-treated cancer patients — with a progression-free survival rate of only 2.5 months. Those are lethal numbers for a mid-stage cancer study.
But Morrison and team found a silver lining: a post hoc analysis identified a subgroup of patients who did better. Whittling the 57 patients reviewed for this readout down to 14 with high monocyte levels, Syndax got a PFS rate of 5.4 months and an ORR of 29%. Wahoo. On to registration studies.
Syndax will launch the Phase Ib trial, with plans keep an eye on biomarkers that might ID patients with enhanced responses, including “analyses exploring the potential of elevated levels of classical peripheral blood monocytes,” the company said.
“The combination of NKTR-214 and entinostat demonstrated a unique synergy in our preclinical models which warrants further study in the clinic,” said Jonathan Zalevsky, SVP and CSO of Nektar. “Importantly, we observed elevated levels of cytokine-positive tumor-infiltrating cytotoxic T cells following treatment with the combination. We believe this important preclinical finding could translate to improved tumor responses in patients who have become refractory to checkpoint inhibitors. We look forward to working with Syndax as this combination advances into the clinic.”
Financial details of the deal weren’t disclosed.
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At-Home Physiotherapy Exercises for Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and degeneration of the neurons.
Credit: stockfour/Shutterstock.com
MS affects approximately 1 – 2.5 million people worldwide. It is common in young adults, and often results in non-traumatic disability. Loss of mobility greatly impacts employment and other day-to-day activities. Exercise and physiotherapy play a positive role in the rehabilitation of patients with MS.

Benefits of exercise in patients with MS

Exercise has a range of benefits in patients with MS, and they are:
  • Improved mood
  • Enhanced strength and mobility
  • Boosted self-esteem/self-confidence
  • Lowered overall fatigue
  • Reduced weight gain
  • Enhanced function of bowel and bladder
Initially, people with MS feel tired when they start exercising, however, slowly they get accustomed to it.

Setting up exercise goals

Patients with MS are advised to consult the healthcare provider, and develop an exercise program according to their health condition. Healthcare provider can help achieve the patient’s goal by monitoring their progress. Consulting a physical therapist can help identify specific exercises based on the patient’s need. The patient can keep track of their own progress by noting down the regular exercises.
Success of home-based program depends on whether or not it is enjoyable, varied, goal-oriented, and realistic. Home-based physical therapy programs have certain compliance issues including exhaustion, poor motivation, depression, lack of support from close family members and friends, time limitations, and cognitive dysfunction.

Types of exercises

Exercise programs of the patients include several types of exercises such as stretching, aerobic exercise, and strength-training.

Stretching

Stretching enhances the flexibility of muscles which help in performing day-to-day activities, and it also prevents injuries.
  • Spend 10 minutes daily for stretching.
  • Before stretching, a person should do warm-up for 5 to 10 minutes to prevent injuries.
  • Stretch gently. The duration of each stretch should be 30-60 seconds. It is important to stretch the major muscle groups in the body.

Aerobic activity

Walking, swimming, cycling, and water aerobics are some of the common aerobic activities for an individual with MS.
  • A minimum duration of 150 minutes of moderate-intensity workout per week is recommended by the experts.
  • It is advisable to increase the aerobic activity slowly. Initial days of workout should be for shorter durations, and the duration of workout should be increased gradually.
  • Several 10-minute periods can be used for working out in a day when the person has time constraints.

Strength training

Strength training is a crucial part of exercise regimen as it helps strengthen the muscles.
  • Strength training exercises are recommended at least twice a week.
  • Varieties of strength training exercises should be included in the regimen as it helps improve major muscle groups present in the body.
  • Core strength exercises should be followed as they help strengthen the muscles of stomach, back, and, the surroundings of pelvis.

Important checkpoints to avoid problems

The following checklist can help the individual with MS in preventing problems associated with home-based exercise regimen.
  • Avoid doing excess workout initially, instead start slowly.
  • Proper hydration is required before, during, and after the exercise.
  • The person with MS should stay cool while exercising. Fan or other cooling devices can be used during the workout sessions.
  • Avoid exercising when MS symptoms are exacerbated. It is recommended to take rest and save the energy during these periods.
  • Suitable footwear should be used during the exercise.
Reviewed by HH Patel, M.Pharm

Sources

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Growth hormone might completely transform treatment for stroke survivors


Less fatigue and better recovery of cognitive abilities such as learning and memory. These may be the results of growth hormone treatment after a stroke, an experimental study of mice published in the journal Stroke suggests.
“We hope that this work can pave the way for clinical studies involving the use of human growth hormone as treatment in the rehabilitation phase after a stroke,” says Jorgen Isgaard, professor of endocrinology at Sahlgrenska Academy, University of Gothenburg, Swden, who also serves as a professor at the University of Newcastle, Australia.
Treatment and rehabilitation after a stroke is a challenge, both for the victims and those around them. Recovery often involves a long and difficult process to repair the speech function, memory, the ability to think and concentrate and more. Worry, anxiety and severe fatigue are also common among those who have survived a stroke.
The current study is based on research conducted in collaboration between the universities of Gothenburg and Newcastle. The results show a link between growth hormone and improved cognition after a stroke as well as the possible mechanisms that may be responsible.
The fact that growth hormone generally has positive effects on cognition after brain damage has been found in previous studies. On the other hand, this is the first time the effect of growth hormone is being tested after a stroke, and the results are regarded as being very positive.
The mice in the study, all with induced strokes, were treated with either an infusion of growth hormone or with placebo for four weeks. In the last week of treatment, they were tested individually in separate cages with touch screens.
The animals were exposed to visual symbols in different combinations in which a correct pressure with a paw on the screen gave a reward in the form of a sugar solution. The mice that received the growth hormone performed correctly in 8 out of 10 cases, compared with 6 out of 10 for the control group. After conclusion of the experiments, researchers also analyzed a number of growth factors and biomarkers in the injured area of the brain.
“The most important new finding is that growth hormone improves cognition after a stroke compared with controls. If this finding holds true for humans, it can lead to a breakthrough in terms of treatment that facilitates rehabilitation and quality of life after a stroke,” says Jorgen Isgaard.
Growth hormone was also found to promote plasticity in the brain. The treatment led to higher levels of markers that reflect, among other things, the formation of new blood vessels, repair of nerve damage and reduced loss of brain tissue compared to controls.
Now researchers hope to secure more funding to begin clinical trials and examine whether growth hormone treatment can also be successful if some time has passed after the onset of a stroke.
“This has the potential to completely transform the treatment of people who survive a stroke,” says Jorgen Isgaard.
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Researchers uncover the cause of rheumatoid arthritis

A team of researchers led by Osaka University have identified the cellular network involved in initiating and maintaining rheumatoid arthritis.
Credit: sciencepics/Shutterstock.com
The researchers suggest that this network can be targeted using a novel immunotherapeutic approach that will reduce joint inflammation.
In a mouse model of the disease, the team found out how Th17 cells interact with other cells at the site of inflammation to influence the production of inflammatory molecules called cytokines.
Chronic inflammatory disorders such as the autoimmune disease rheumatoid arthritis involve the action of various cytokines produced by the immune system. One such cytokine is IL-17, which is produced by TH17 cells.
Although TH17 cells are known for the role they play in autoimmune disease, researchers have been unclear on how they control other inflammatory cells.
As reported in the journal Immunity, Keiji Hirota and colleagues have now shown that the inflammatory cytokine GM-CSF is essential for the development of arthritis in mice.
The team found that GM-CSF produced by both stromal cells in the connective tissue and T cells contributed to joint inflammation in the animals, but only stromal cell-derived GM-CSF was required to initiate arthritis.
“We also showed that stromal cells secreted GM-CSF in response to stimulation by IL-17 from inflammatory Th17 cells,” says Hirota.
In addition, the study found that GM-CSF was secreted by a group of innate immune cells, the cells involved in non-specific defense mechanisms.
These cells expanded in number within inflamed joints in response to the production of IL-17 by Th17 cells and other inflammatory cytokines. This contributed to the development and maintenance of rheumatoid arthritis in the mice.
Our findings outline an inflammatory network controlled by autoimmune Th17 cells and involving stromal cells and innate immune cells, which leads to the onset and development of autoimmune arthritis.”
Shimon Sakaguchi, Co-Author
When the researchers removed the cells that produce GM-CSF from the joint lining (synovium), they observed a significant reduction in the severity of arthritis.
“This suggests the usefulness of developing such a novel immunotherapeutic approach that targets the cellular network to reduce chronic joint inflammation,” concludes Sakaguchi.
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LivaNova comments on reconsideration of its coverage for therapy


LivaNova PLC issued a statement in regard to the U.S. Centers for Medicare & Medicaid Services’ publication of a tracking sheet to reconsider its National Coverage Determination for the Company’s Vagus Nerve Stimulation Therapy System for Treatment-Resistant Depression: LivaNova has been engaged with CMS on this important issue and submitted a letter to CMS requesting a formal reconsideration of the NCD for VNS Therapy for patients with TRD. The Company is encouraged that CMS has taken this initial step, which may provide access to this important therapy for TRD that has been a Medicare non-covered indication for more than a decade. A change in the Medicare coverage status of VNS Therapy for TRD that ensures adequate patient access to this important therapy would be a positive outcome for patients and physicians. The posting of the National Coverage Analysis tracking sheet has opened the 30-day public comment period. Interested parties may comment on the NCA tracking sheet until June 29 as CMS brings greater attention to this important public health issue. Over the last decade, a significant body of new evidence has emerged showing that the addition of VNS Therapy is effective in reducing symptoms in patients with TRD. We look forward to working with CMS as they consider a change in Medicare coverage
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AbbVie cut by Credit Suisse on competitive concerns


AbbVie Inc ABBV 3.56%‘s stock is up 51 percent year-over-year, but its lifeblood may be draining.

The Rating

Credit Suisse analysts Vamil Divan and Michael Morabito downgraded AbbVie to Underperform and lowered their price target from $104 to $89.

The Thesis

The analysts attribute AbbVie’s run to Humira legal settlements and tax reform coupled with high pipeline expectations.
“The first two points have played out but we see pipeline enthusiasm now being stretched, at best limiting room for further upside over the next 12 months,” Divan and Morabito wrote in a note.
They identify long-term fundamental concerns, particularly with emerging competition limiting Humira’s longevity.
The fourth-quarter entry of biosimilars in Europe is seen to catalyze “rapid erosion” of Humira sales, while U.S. earnings are to be stunted by impending biosimilar competition, decreased ability for AbbVie to increase prices, the impact of copay accumulator programs, and action to work around “rebate traps” ahead of rival emergence.
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FDA OKs First Artificial Iris


The US Food and Drug Administration (FDA) has approved the first artificial iris for use in adults and children with congenital aniridia or iris defects due to other reasons or conditions, such as albinism, traumatic injury or surgical removal due to melanoma.
The CustomFlex Artificial Iris (HumanOptics AG) is a surgically implanted device made of thin, foldable medical-grade silicone and is custom-sized and colored for each individual patient. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.
“Patients with iris defects may experience severe vision problems, as well as dissatisfaction with the appearance of their eye,” Malvina Eydelman, MD, director of the Division of Ophthalmic, and Ear, Nose and Throat Devices at the FDA’s Center for Devices and Radiological Health, said in a news release.
“Today’s approval of the first artificial iris provides a novel method to treat iris defects that reduces sensitivity to bright light and glare. It also improves the cosmetic appearance of the eye in patients with aniridia,” said Eydelman.
Congenital aniridia, a rare genetic disorder in which the iris is completely or partially absent, affects about 1 in 50,000 to 100,000 people in the United States.
The safety and effectiveness of the CustomFlex Artificial Iris was shown primarily in a non-randomized clinical trial of 389 adult and pediatric patients with aniridia or other iris defects.
More than 70% of patients reported a significant decrease in light sensitivity and glare as well as an improvement in health-related quality of life following implantation of the device. In addition, 94% of patients were satisfied with the artificial iris’ appearance, according to the FDA.
The study showed low rates of adverse events associated with the device and surgical procedure.
Complications associated with the CustomFlex Artificial Iris included device movement or dislocation, strands of device fiber in the eye, increased intraocular pressure, iritis, adhesion of the iris to the cornea or lens, and the need for secondary surgery to reposition, remove or replace the device.
Complications associated with the implant procedure included increased intraocular pressure, blood leakage in the eye, cystoid macular edema, secondary surgery, corneal swelling, iritis, and retinal detachment.
The CustomFlex Artificial Iris should not be used in eyes with any of the following conditions: uncontrolled or severe chronic uveitis, microphthalmus, untreated retinal detachment, untreated chronic glaucoma, cataract caused by rubella virus, rubeosis, certain kinds of damaged blood vessels in the retina, and intraocular infections. It is also contraindicated for patients who are pregnant.
The CustomFlex Artificial Iris had a breakthrough device designation and was approved through a premarket approval application (PMA), which is the most stringent type of device marketing application and generally required for high-risk devices.
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