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Thursday, July 11, 2019

Mentally Stimulating Activities and Cognitive Impairment

The number of mentally stimulating activities adults participated in — and their timing — was tied to their risk of age-related memory loss, a prospective study of 2,000 older adults showed.
Engaging in two or more cognitively stimulating activities — such as reading books, computer use, crafts, social activities, and playing games — in late life was tied to a lower risk of incident mild cognitive impairment (MCI), reported Yonas Geda, MD, of the Mayo Clinic in Scottsdale, Arizona, and colleagues.
Engaging in any two activities in late life decreased MCI risk by 28%; three activities dropped the risk by 45%, and four activities lowered the risk by 56%, they wrote in Neurology.
“It is never too late,” Geda told MedPage Today. “If I am 84, I can still engage in mental activities and have good reason to assume I will have a better chance of reducing my risk of mild cognitive impairment.”
The analysis builds on the authors’ previous work that showed stimulating activities may diminish the risk of MCI in older people, even APOE4 carriers.
The earlier study generated a number of questions, noted co-author Janina Krell-Roesch, PhD, formerly of the Mayo Clinic and currently with the Karlsruhe Institute of Technology in Germany. In response, “this new research looked at two different things,” she told MedPage Today. “Does the timing of the activities matter? And does the number of activities matter?”
The current research followed 2,000 cognitively unimpaired people who were ages ≥70 in the Mayo Clinic Study of Aging, monitoring them for clinical progression to MCI over a median of 5 years. Participants completed a self-reported survey at baseline about the timing, number, and frequency of engaging in five mentally stimulating activities: reading books, computer use, social activities, playing games, and craft activities.
At baseline, participants had a median age of about 78 and education level of 14 years. Half of the group (49.9%) was male. Over the follow-up period, 532 people developed new onset MCI.
The number of mentally stimulating activities participants engaged in at midlife (from the ages of 50 through 65) showed no significant association with the risk of new onset of MCI. But in late life (ages ≥66), engaging in more activities was tied to a significantly reduced risk of incident MCI.
Engaging in any two activities in late life showed an HR for MCI of 0.72 (95% CI 0.53-0.99). Engaging in any three late-life activities had an HR of 0.55 (95% CI 0.40-0.77), four activities showed an HR of 0.44 (95% 0.30-0.65), and five had an HR of 0.57 (95% CI 0.34-0.96).
Computer use in midlife, computer use and craft activities in late life, and social activities, game playing, and computer use in combined late-life and midlife stages all were linked to a decreased incidence of MCI. In late life, a decreased risk of MCI was tied to reading books, playing games, or engaging in craft or social activities at least 2 to 3 times a month, or using a computer at least 5 to 6 times a week.
This analysis provides “evidence that there is an association between quality and quantity of mentally stimulating activities, which include both cognitive and social leisure activities, and reduced risk or slowing of the emergence of mild cognitive impairment,” noted Rebecca Amariglio, PhD, of Brigham and Women’s Hospital in Boston, and colleagues, in an accompanying editorial.
“The findings of this report could be of value to clinicians attempting to counsel midlife and older adults about how to stave off or delay the onset of mild cognitive impairment,” they added. While mentally stimulating activities may be low-cost interventions that could decrease the risk of cognitive decline,” important questions remain about why mentally stimulating activities remain primarily more protective in late life compared with midlife.”
The study has several limitations: it was observational and did not provide evidence that cognitively stimulating activities reduce incident cognitive impairment. Low engagement in activities may be the result of incipient MCI; other unmeasured variables also may account for the associations found in the study. Activities were self-reported and participants were asked to remember how often they engaged in activities as far back as middle-age, up to 2 decades before the study began.
Last Updated July 10, 2019
The study was supported by the NIH, the National Institute on Aging, the National Institute of Mental Health, the Robert Wood Johnson Foundation, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program, the GHR Foundation, the Mayo Foundation for Medical Education and Research, the Edli Foundation, and the Arizona Alzheimer’s Consortium.
Researchers disclosed relevant relationships with Eli Lilly, Lysosomal Therapeutics, Biogen, Lundbeck, the Alzheimer’s Treatment and Research Institute, AstraZeneca, Roche, Merck, Genentech, and Janssen Alzheimer Immunotherapy.
The editorialists disclosed no relevant relationships with industry.

Indivior fights off generic challenges but the threat of litigation remains

Today’s 16% rise in Indivior’s share price has less to do with the group selling more of its opioid dependency treatment products than with the inability of its generic competitors to sell theirs.
Indivor thrilled the market with substantially upgraded full-year guidance for 2019, as it appeared that generics companies like Dr Reddy’s and Mylan had failed to convince patients to try their version of Indivior’s Suboxone film. The product, which has continued to defy conventional wisdom around generic sales erosion, still accounts for the majority of Indivior sales.
Another demonstration of Suboxone’s continued grip on the US opioid substitution market is that the product still makes up over 70% of opioid substitution products. This figure includes the 24% of sales contributed by the authorised generic Indivior launched in February as a countermeasure to copycats.
Despite the strong showing today Indivior’s shares, which have been falling since June 2018 when the FDA approved generic versions of Suboxone film, are still down 55% on the year.
Settling for a billion
Indivior’s guidance came on the same day that its former parent, Reckitt Benckiser, announced that it had reached an agreement with the Department of Justice and Federal Trade Commission to pay up to $1.4bn to settle claims it had participated in fraudulent marketing schemes to increase sales of Suboxone.
As the current owner of Suboxone, Indivior was also named in the investigation. But the UK company has denied the allegations, which it has described as “self-serving” and based on events four years before Indivior was spun out of Reckitt in 2014.
Reckitt’s $1.4bn settlement is one of the biggest the industry has seen, though it is still eclipsed by Glaxosmithkline’s eye-watering $3bn payout for failing to disclose safety information around diabetes drug Avandia.
Read-through?
While it might not be pharma’s largest payout, $1.4bn is still a large amount of money even if the compay on the hook for it has a market cap of £47bn. And here is the rub for Indivior, which for litigation purposes has far shallower pockets than Reckitt. So far Indivior, which only has a market cap of £389m ($480m), has set aside $438m for any form of payout.
Indivior has also chosen to go to trial to refute the DoJ/FTC allegations. A hearing is not expected until 2020 and could take up to two years to conclude, meaning any overhang to Indivior shares could continue for another three years.
But what today’s announcement by Reckitt shows is that it is possible to settle with the DoJ without any requirement to admit wrongdoing. This non-prosecution type agreement is important if Indivior wants to retain its current access to US government Medicare and Medicaid contracts, which currently represent around half of its US business.
As to the size of any settlement for which Indivior might be liable, some analysts are not expecting the amount forked out by Reckitt, which would effectively bankrupt Indivior. “The DoJ knows that they are not going to get $1.5bn out of Indivior, but they might get a bit more than what Indivior has set aside. If they can get $600m or $700m and settle then everyone can move on,” said one healthcare analyst.
Until then, despite its success in holding off the more immediate generic threats, Indivior will still remain a tricky investment case.

Soliton Expands Clinical Trial Sites to include Skin Care Physicians

Soliton, Inc. (SOLY) (“Soliton” or the “Company”), a medical device company with a novel and proprietary platform technology licensed from The University of Texas on behalf of the MD Anderson Cancer Center (“MD Anderson”), today announced that the company has identified an additional site and supervising physician for its upcoming expanded pivotal Cellulite Trial. The site is the second of four planned sites for the pivotal trial.
The proof-of-concept trial was conducted by Dr. Michael S. Kaminer at SkinCare Physicians in Boston in collaboration with Dr. Elizabeth L. Tanzi of Capital Laser and SkinCare in Chevy Chase, MD. The expanded Cellulite Clinical Trial will now include subjects treated at SkinCare Physicians, supervised by Dr. Kaminer, added to the subjects being treated at Capital Laser. Drs. Kaminer and Tanzi are members of the Company’s Scientific Advisory Board.

Novan up on advancement of SB206 Phase 3

Novan (NOVN +2.5%) perks up, albeit on light volume, following its announcement that its Phase 3 studies (B-SIMPLE 1&2) evaluating SB206 for the treatment of molluscum contagiosum are more than 50% enrolled.
Topline data should be available in Q1 2020.

Enzo Biochem to launch direct-to-consumer STI testing

Aimed at stoking growth in its diagnostic tests, Enzo Biochem (ENZannounces the following key initiatives:
New York State Health Department approval for oral and rectal sexually transmitted infection (STI) (recently OK’d for its gonorrhea and chlamydia tests for oral and rectal specimens).
Create a direct-to-consumer business for STI tests.
Build a new lab-to-labs business model that leverages the scale of its central lab with smaller labs.
Expand offerings to clinical research organizations, academic research institutions and the pharma industry.

Endo cut to Sector Perform from Outperform by RBC

Target $6 from $11

Aimmune on ICER Final Report on AR101 for Peanut Allergy

Aimmune Therapeutics (Nasdaq: AIMT), a biopharmaceutical company developing treatments for life-threatening food allergies, cautions stakeholders against drawing conclusions from the Institute for Clinical and Economic Review’s (ICER’s) final report on emerging desensitization treatments for peanut allergy, released yesterday. In its review, ICER fails to incorporate available data on both long-term outcomes and quality-of-life. ICER’s analysis and the public meeting discussion discounted patient and community perspectives on the physical, social and psychological benefits of desensitization.
The resulting final report is biased against immunotherapy, generally, and fails to specifically capture the full value of AR101. Aimmune joins advocates and clinical experts asking payers and policymakers to engage in more thoughtful, unbiased consideration of available evidence—including patient perspectives on quality-of-life improvements and relief from the stress and fear of accidental exposure—when evaluating emerging treatments for peanut allergy.
In clinical trials, AR101, Aimmune’s investigational biologic drug for use in oral immunotherapy, has demonstrated the ability to increase the median tolerated dose of peanut protein by 100-fold in each of its two pivotal Phase 3 clinical trials. While the report found AR101 to be cost-effective well below traditional health economic thresholds, ICER failed to acknowledge the availability of the positive long-term efficacy and quality-of-life data from the PALISADE open label follow-on study, as well as the clinical outcomes data from the European Phase 3 ARTEMIS trial. These data were recently presented at the 2019 European Academy of Allergy and Clinical Immunology (EAACI) Congress and shared with ICER in May under its “academic in confidence” policy and throughout the review process including the June 11 public meeting. ICER did not acknowledge or incorporate the existing data in its final evidence report or the associated cost-effectiveness analysis.
“From the onset, we have believed that ICER’s attempt to assess the value of AR101 was premature, based too heavily on theoretical discussions rather than real-world insight, and omitted valuable patient perspective. Critical data from our Phase 3 trial program continues to emerge, specifically new patient-reported quality-of-life data that were excluded from the analysis,” said Jayson Dallas, M.D., President and Chief Executive Officer of Aimmune. “We believe this final report raises more questions than it answers and should be viewed as an early starting point for future conversations—not the final word—about the value of AR101.”
Additionally, ICER failed to consider the potential for long-term disease modification consistent with allergen immunotherapies and mischaracterized the allergic response associated with immunotherapy as a harm, rather than an expected, well understood and easily managed part of the immunotherapy process. With all immunotherapy, allergic reactions are expected and acceptable in the short term in exchange for long-term desensitization to protect against accidental exposure. In clinical trials, median tolerated dose for AR101-treated patients improved from 10mg at baseline to 1000mg at month 12 to 2000mg at month 18—demonstrating both the potential for long-term disease modification and the potential for significant protection against the average real-world reaction-provoking exposure of 125mg, or half a peanut.
“The peanut allergy community, including patients, families, advocates and allergists, are well aware of and well prepared for the possibility of reactions as part of the shared decision-making process involved in immunotherapy,” said Stephen Tilles, M.D., Senior Director of Medical Affairs at Aimmune, and a nationally recognized 20-plus-year clinical expert who represented Aimmune at ICER’s public meeting. “Not every patient has a reaction with immunotherapy, but patients and families live every day with fear and anxiety of unpredictable, potentially life-threatening reactions due to accidental exposure. If approved, AR101 will offer patients the potential for meaningful desensitization using a clinically developed, rigorously-tested treatment in close collaboration with their allergists.”
The FDA’s Allergenic Products Advisory Committee (APAC) will review Aimmune’s Biologics License Application (BLA) for AR101 at its meeting scheduled for September 13, 2019. The FDA accepted the BLA for AR101 in March 2019 and previously informed Aimmune that completion of its review would be targeted by late January 2020. The FDA granted AR101 Fast Track Designation in September 2014 and Breakthrough Therapy Designation in June 2015 for peanut-allergic children and adolescents ages 4 to 17.