Eisai, Sysmex eye developing Alzheimer’s blood test

Sysmex Corporation and Eisai Co., Ltd. are pursuing a joint project to develop a method of diagnosing Alzheimer’s disease (AD) using blood, presented two posters showing the most recent data from the project. The presentations took place at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) conference, from December 4 to 7, 2019, in San Diego, California. At CTAD, Sysmex demonstrated on behalf of the two companies the possibility of understanding amyloid pathology in the brain from the brain-derived amyloid beta (Abeta) in plasma measured using its protein measurement platform, the HISCLTM series of fully automated immunoassay analyzers.

The total number of those living with dementia across the world is projected to reach 82 million in 2030 and 152 million in 2050, with the total global societal cost of dementia stemming from direct medical and social care costs and lower productivity being estimated to reach 220 trillion yen in 2030.(1) In Japan, the number of those with dementia is thought to have reached approximately 4.62 million in 2012 and is projected to grow to 7.30 million in 20252, with the total societal cost of this disease being estimated to be equivalent to 4.1%(3) of the gross domestic product (GDP) in 2025 (25.8 trillion yen(4)). Of these sufferers, those living with AD is thought to account for more than 60% of those living with dementia.(2)

It is conceivable that AD is a disease that results in synaptic dysfunction and neuronal cell death due to the tau deposition in neurons triggered by Abeta aggregation on the outside of neurons.

These brain changes cause the cognitive impairment and psychological and behavioral symptoms, suggesting that the Aβ aggregation and accumulation inside the brain are caused by AD before the presence of cognitive impairment appears, thus, it is believed that early diagnosis and early intervention is more effective in therapies targeting Abeta. Currently, amyloid PET and the plasma Abeta1-42/ Abeta1-40 ratio in cerebrospinal fluid (CSF) are used for detecting amyloid aggregates in the brain, but this puts significant burden on patients in terms of access, costs, and their physical wellbeing.(5)

In February 2016, Sysmex and Eisai signed a comprehensive non-exclusive agreement aimed at the development of new diagnostic tests in the field of dementia. By leveraging each other’s technologies and knowledge, the objective has been to discover next-generation diagnostic reagents that will enable early diagnosis of dementia, selection of the most appropriate treatment options, and regular monitoring of the effects of such treatments.

At the Alzheimer’s Association International Conference (AAIC) held in July 2019, Sysmex and Eisai presented their joint research on the correlation (Spearman’s rank correlation coefficient (rs)6=0.502, p<0.001) between the Abeta1-42/ Abeta1-40 ratio in CSF and the Abeta1-42/ Aβ1-40 ratio in plasma, and demonstrated that it may be possible to understand amyloid pathology in the brain by measuring the plasma Abeta1-42/ Abeta1-40 ratio. Subsequently, the two companies have examined the correlation between the plasma Abeta1-42/ Abeta1-40 ratio and amyloid PET.

Sysmex and Eisai are engaged in joint development aimed at creating a simple method of

diagnosing AD from a blood sample. At CTAD, Sysmex demonstrated that it may be possible to understand pathological processes in the brain by measuring the plasma Abeta1-42/Abeta1-40 ratio based on the analysis result of the plasma Abeta1-42/Abeta1-40 ratio measured with the HISCL series as a predictive factor for Abeta PET positivity. Also it was presented a technique for verifying that the HISCL measuring system correctly captures Abeta in plasma on that occasion.

https://www.marketscreener.com/EISAI-CO-LTD-6492461/news/Eisai-Sysmex-Presents-Academic-Report-with-a-View-to-Creating-a-Simple-Method-of-Diagnosing-Alzhei-29698685/

Earnings after Monday’s close

CDMO, PHR

https://seekingalpha.com/news/3524630-notable-earnings-after-monday-s-close

uniQure Follow-Up Phase IIb Data on Hemophilia Trial at ASH19

~ Sustained FIX Activity at Therapeutic Levels¹ Up to 50% of Normal at One Year After Administration of Etranacogene Dezaparvovec in Phase IIb Study ~

~ Zero Bleeds and No Requirement for Immunosuppression in One Year Following Dosing with Etranacogene Dezaparvovec ~

~ Long-term Clinical Benefit and Tolerability of AMT-060 Maintained in All Patients Through up to 4 Years of Follow-Up ~

~ Investor Webcast on Monday, December 9, 2019 at 7:00 a.m. EST ~

https://www.marketscreener.com/UNIQURE-N-V-15712155/news/uniQure-Announces-One-Year-Follow-Up-Data-from-the-Phase-IIb-Study-of-Etranacogene-Dezaparvovec-and-29698545/

BeiGene Announces Clinical Data on BRUKINSA™ (Zanubrutinib) at ASH19

Oral presentations on data from two clinical trials in chronic lymphocytic leukemia or small lymphocytic lymphoma

Poster presentation on data from clinical trial of BRUKINSA combined with tislelizumab in B-cell malignancies

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, today announced clinical data from three trials of its BTK inhibitor BRUKINSA™ (zanubrutinib) were presented at the 61^st American Society of Hematology (ASH) Annual Meeting in Orlando, FL. In two oral presentations of BRUKINSA in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the drug candidate demonstrated consistent safety and a high overall response rate (ORR); in the poster presentation of BRUKINSA combined with BeiGene’s investigational anti-PD-1 antibody tislelizumab in patients with previously treated B-cell malignancies, the combination treatment showed preliminary efficacy and was generally well tolerated.

“The data presented today showing clinical activity and tolerability of BRUKINSA in patients with CLL or SLL are promising for its potential use in patients living with these cancers,” said Constantine S. Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at the Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia. “BTK inhibitors have become an important standard of care for B-cell malignancies, offering the potential for durable responses with manageable safety profiles. It’s encouraging to have more evidence that zanubrutinib can be effective in treating CLL or SLL, including in patients with del(17p) who typically have a worse prognosis and few treatment options.”

https://www.marketscreener.com/news/BeiGene-Announces-Clinical-Data-on-BRUKINSA-trade-Zanubrutinib-at-the-61st-American-Society-of-He–29698553/

Rocket Pharma Prelim Phase 1 Anemia Trial Results at ASH19

—US Phase 1 Trial Establishes Feasibility of Commercial “Process B” Vector/Cell Manufacturing in FA—

—Preliminary Data Demonstrate Evidence of Early Engraftment Without Conditioning Four to Six Months after Administration of Gene Therapy—

—“Process B” Drug Product VCN 2-3x Higher Than That Administered to Optimally-Treated “Process A” Patients—

https://www.marketscreener.com/ROCKET-PHARMACEUTICALS-I-40561561/news/Rocket-Pharmaceuticals-Presents-Promising-Preliminary-Results-from-Phase-1-Trial-of-Commercial-Gra-29698574/

64M Americans have tried CBD and now the FDA says it could cause liver damage

Brandon Warne, a Minnesota Twins beat reporter for the sports news outlet Zone Coverage, started taking cannabidiol (CBD) in August after growing increasingly frustrated with his depression and anxiety medications over the past four years.

“I was just at a point where nothing was working for me,” Warne, 33, of Minnesota’s Twin Cities area, told MarketWatch. “I was just trying to branch out because I was just so upset [and] distraught with my lack of progress towards mental health.”

Under the guidance of his psychiatrist and therapist, Warne started taking CBD and pared down his medication list. He tapered off the antidepressants bupropion GSK, +0.66%  and Effexor PFE, +0.68%  , but continued to take his anti-anxiety medication, buspirone TEVA, +1.02%  , after experiencing “wicked side effects” from trying to go off of it. He now takes CBD in the form of a 0.5-ml dose of Clean Remedies full-spectrum hemp extract oil every morning, and plans to eventually try to taper the buspirone as well.

Warne, who received his diagnoses after his grandfather’s death, wonders whether he was misdiagnosed. But the results he has seen since taking CBD, he said, have been “moderately positive.” “I’ve been feeling great since I got off my meds,” he said.

‘We remain concerned that some people wrongly think that the myriad of CBD products on the market, many of which are illegal, have been evaluated by the FDA and determined to be safe, or that trying CBD ‘can’t hurt.’

— Amy Abernethy, FDA principal deputy commissioner

Warne isn’t entirely sure whether it’s the CBD oil or being off his meds that’s causing the improvement, but he is willing to continue trying CBD when he’s done with his current bottle. He said he still has “research” to do on the matter — and a new FDA warning backs him up.

The Food and Drug Administration said late Monday that what you don’t know about CBD might hurt you and warned that it could cause serious health problems, including liver damage.

The warning comes as millions of consumers have jumped on board with the non-psychoactive cannabis compound for reasons relating to health, wellness and recreation, and CBD has popped up on restaurant menus, in post-workout salves and in bath bombs.

The FDA sent letters warning 15 companies for illegally selling CBD-containing products. The federal agency also updated its position to clarify that the substance increasingly infused in pills, lotions, food products and wellness beverages “has the potential to harm you, and harm can happen even before you become aware of it.”

“We remain concerned that some people wrongly think that the myriad of CBD products on the market, many of which are illegal, have been evaluated by the FDA and determined to be safe, or that trying CBD ‘can’t hurt,’” Amy Abernethy, the FDA’s principal deputy commissioner, said in a statement.

The only CBD product approved by the FDA is the prescription drug Epidiolex, which treats pediatric epilepsy. It’s illegal to market CBD as a dietary supplement.

The compound can cause liver injury, interact with other drugs, and increase the risk of drowsiness and sedation when used with alcohol, the FDA said. Studies using lab animals have also shown negative impacts on the male reproductive system, though the takeaway for human patients remains unclear, the FDA said.

The agency also provided a list of potential side effects related to CBD, including sleepiness, diarrhea and/or a decrease in appetite, and mood changes such as agitation and irritability.

Many questions, not many answers

Scientists still don’t know what happens if a person consumes CBD daily for sustained time periods; the compound’s effect on children who take CBD, growing fetuses or breastfed newborns; its interactions with herbs and botanicals; and whether it leads to the same male reproductive problems in men as observed in animals, the FDA said.

What’s more, the FDA is concerned about “a lack of appropriate processing controls and practices”: Many products tested by the FDA have contained different CBD levels than what manufacturers claimed, and there have been reports of products containing unsafe levels of pesticides, heavy metals and THC, the agency said.

“I still don’t think it’s so harmful that I shouldn’t use what I have,” Warne said in response to the new FDA warning. “But it certainly makes me question how settled the science is … and maybe it’s not as ironclad as I thought it was before.”

64 million Americans have tried CBD

Research published this year by the consumer-data firm MRI-Simmons estimated that 3.7 million U.S. adults were CBD consumers, with a median age of 45. Even more appear to have dabbled in the substance: Some 64 million Americans — 26% of the country — report having tried CBD in the last two years, according to a nationally representative Consumer Reports survey of more than 4,000 people conducted in January. One in seven of those respondents reported daily use.

And many CBD users use the compound for its health potential, though their outcomes tend to be mixed.

More than a third of respondents to the Consumer Reports survey said they used CBD to reduce stress or anxiety or promote relaxation; 63% of those people said the compound was “extremely or very effective” at doing so, while 16% said it was not at all or only slightly effective. Nearly one in four respondents said they used CBD to help with joint pain, with 38% calling it “extremely or very effective” and 27% saying it was slightly or not at all effective.

The Mayo Clinic says that “although some research appears to indicate that CBD might hold benefit for treating anxiety-related disorders, more study is needed.” And physician Peter Grinspoon, writing on the Harvard Health Blog, noted that an animal study had shown that applying CBD to the skin could help lower arthritis-related pain and inflammation. “More study in humans is needed in this area to substantiate the claims of CBD proponents about pain control,” he added.

Warne is not alone in using CBD to replace or supplement a medication: 30% of respondents to the Consumer Reports survey said they had taken CBD in addition to a prescription or over-the-counter medication, while 22% said they replaced the medication with CBD entirely. A third of those who replaced a medication with CBD said that the drug was a prescription anti-anxiety drug.

Still, Warne called the FDA’s words of caution “prudent” and agreed that more research should be conducted on CBD’s benefits and risks.

“Hopefully it stands up — because otherwise, we’re kind of all owed an explanation for why this was pushed on us for the past year or however long this has been popular,” he said. “Hopefully we get an explanation one way or the other.”

https://www.marketwatch.com/story/64-million-americans-have-tried-cbd-and-now-the-fda-says-it-could-cause-liver-damage-2019-11-27?siteid=rss&rss=1

Ash 2019 – J&J overshadows Bluebird’s registrational reveal

This year’s Ash features numerous duelling anti-BCMA therapies in multiple myeloma, and the first clinical data for JNJ-4528 impress.

With Bluebird missing the deadline for getting its registrational Karmma dataset into the Ash conference, the way was left clear for Johnson & Johnson to seize the early spotlight. Today’s Ash presentation of the first human data with J&J’s anti-BCMA Car-T project JNJ-4528 has shown a staggering 100% remission rate.

Bluebird/Bristol-Myers Squibb did unveil the Karmma data yesterday, but only by press release. The results certainly seem good enough to secure approval for ide-cel/bb2121 in late-line multiple myeloma, but relapses remain the elephant in the room, and care has to be taken when attempting cross-study comparisons owing to differing patient characteristics.

In Karmma, for instance, all 128 treated subjects had failed at least three therapy lines, and 84% were triple-refractory. The key efficacy data – a 73.4% overall response rate, including 31.3% complete remissions – look reasonable compared with the 77% ORR (31% CR) rates seen in the earlier study of bb2121 in subjects who had failed an average seven prior therapies.

However, the worry is relapses: remissions in Karmma lasted only 10.6 months on average, and median progression-free survival was 8.6 months. Against such a backdrop, the threat of J&J’s JNJ-4528 in what is already a highly competitive field has suddenly become real.

At Ash today J&J said its Cartitude-1 trial of JNJ-4528 had so far treated 29 subjects, 86% of whom were triple-refractory, and 31% of whom were penta-refractory. All patients responded to JNJ-4528, an amazing 69% showing complete remission or better.

Source: Dr Deepu Madduri & Ash.

Followers of J&J will thus breathe a sigh of relief. The company had licensed JNJ-4528, a bispecific Car against two different epitopes on the BCMA protein, from Nanjing Legend, a subsidiary of China’s Genscript Biotech, for $350m up front, but Legend’s own data have since then drawn criticism (Ash 2018 – Legend’s mystery CAR raises more questions, December 3, 2018).

Cartitude-1’s presenting author, Dr Deepu Madduri of Mount Sinai Medical Center, suggested preferential expansion of CD8+ central memory T cells as one reason behind JNJ-4528’s impressive efficacy. That said, the real test is durability, and here it is early days: 27 of the 29 subjects are progression free at a median six months’ follow-up.

It will not go unnoticed that Cartitude-1 and Karmma each featured a report of a patient death owing to cytokine release syndrome. This might be surprising given the prevailing view that this Car-T-related side effect is now largely controllable.

As an interesting aside, Legend is still running its own Chinese study, Legend-2, and will update the results at Ash on Monday. It continues to call its project LCAR-B38M; this is identical to JNJ-4528, though J&J has previously told Vantage that it uses different manufacturing and scale-up processes.

And a separate Car-T asset against multiple myeloma was unveiled at Ash today by another Chinese group, Cellyan Therapeutics. This targets BCMA and CD38, and yielded a 90.9% ORR, with 12 CRs, in 22 multiple myeloma subjects who had failed two to nine prior therapies.

15 of 20 responses were ongoing at 12-72 weeks, said Huazhong University of Science and Technology’s Dr Heng Mei. However, given the differing standards of treatment, any prospective western partner for this project would be well advised to run a confirmatory study in the US – as J&J is doing with JNJ-4528.

Contingent value

So where does this all leave Bluebird and Bristol? For investors ide-cel is an important consideration because it is one of three elements of the contingent value right that Bristol issued when it bought Celgene, Bluebird’s original partner.

The CVR will be triggered if, among other things, ide-cel is approved in the US by 31 March 2021. On the strength of Karmma this is certainly looks achievable, and a filing based on this dataset looks likely to go ahead imminently.

The broader question is how big ide-cel could turn out to be, and unfortunately for Bluebird Karmma provides little solace. A potent though short-lived therapy offers little hope of expanding ide-cel into earlier lines of therapy.

And bb21217, which Bluebird had played up as a potentially improved version of ide-cel, actually looks little better, according to its Ash abstract. Attention now turns to Bristol’s bispecific anti-BCMA MAb CC-93269, whose first clinical data presented at Ash today have impressed.

Ide-cel kicked off the BCMA revolution in multiple meyloma, but by the time this year’s instalment of Ash is over it might look remarkably vulnerable.

https://www.evaluate.com/vantage/articles/events/conferences/ash-2019-johnson-johnson-overshadows-bluebirds-registrational