Everyone’s favourite police dog Stella the Staffie has successful stem cell treatment and will return to work – Gloucestershire Live

Award-winning police dog Stella the staffie has undergone successful stem cell treatment on a shoulder injury to allow her to return to work.

The Staffordshire Bull Terrier, public service animal of the year at the 2015 Animal Hero Awards, damaged her shoulder while doing a demonstration at St James School in Tredworth, Gloucester.

The dog had successful stem cell treatment on Wednesday, December 19, at Vale Vets, in Dursley, and is currently recovering after the operation.

Stellas handler, PC Claire Todd, said: The surgery went really well and Stella is now back to her normal self.

The hardest thing now is trying to keep her quiet. She isnt allowed to exercise for two days, and after that can only go on ten minute long walks each day but she wants to do everything straight away.

Vet Rachel Mowbray, who is the veterinary surgeon for the British agility dog team, carried out the stem cell treatment. Gloucestershire Constabulary helped to pay for the treatment and will welcome Stella back to the drug squad in due course.

PC Todd added: It is amazing to have Stella back to normal and after six weeks she will be able to do everything she used to be able to do, and re-join the force.

I would like to thank Gloucestershire police for the support they have given to Stella and myself.

They have been fully supportive throughout and we are both very grateful.

Stella will undergo laser treatment on Monday, December 23, to assist the recovery process and will need to wear dog goggles as part of the procedure.

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Everyone's favourite police dog Stella the Staffie has successful stem cell treatment and will return to work - Gloucestershire Live

CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative…

VANCOUVER, Washington, Dec. 23, 2019 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today continued promising clinical responses from its metastatic triple-negative breast (mTNBC) Phase1b/2 trial and its trial investigating leronlimab for the treatment of metastatic breast cancer (MBC).

Further data from the first mTNBC cancer patient continues to show no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood and additional reductions in CCR5 expression on cancer-associated cells at 11 weeks of treatment with leronlimab. Additional data in an emergency IND protocol involving one MBC patient demonstrated shrinkage of tumor (via MRI) after three weeks of treatment with leronlimab.

In the first patient, were encouraged to see that after 11 weeks these additional data provide further preliminary evidence of efficacy, as demonstrated by sustained undetectable levels of CTCs and a reduction of cancer-associated macrophage like cells (CAMLs), said Bruce Patterson, M.D., Chief Executive Officer of IncellDx. Thus far, the data have been consistent with previous studies evaluating leronlimab as a long-term therapy for HIV+ patients, with no serious adverse effects reported in the mTNBC trial.

CytoDyns second patient enrolled is a stage 4 MBC patient. The metastasis progressed to the liver, lung and brain. This patient was enrolled through an emergency IND. The patient was on Herceptin and Perjita for over 1.5 years. Herceptin is known to stop working after about 12 months, while Perjita is effective for approximately 1.5 years. This patient received her first injection of leronlimab on November 25, with one 700 mg dose each week.

Regarding the second patient, Nader Pourhassan, Ph.D., president and chief executive officer of CytoDyn, stated: It is very exciting to see ongoing results that demonstrate leronlimabs potential as a therapeutic option to treat patients with mTNBC and MBC with HER2+ condition. This second patient was enrolled in an emergency IND.

Added Dr. Patterson, The results from two subsequent scans of the metastatic lesions for this second patient demonstrated shrinkage of the tumors at both timepoints following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors.

Dr. Pourhassan continued, Due to these very promising clinical data, we feel that the 98% inhibition of metastasis shown by our animal studies may soon become a reality for many cancer patients throughout the world. We are cautiously optimistic and believe we have enough results in an unmet medical need population to justify filing for Breakthrough Therapy Designation in January 2020.

About Triple-Negative Breast CancerTriple-negative breast cancer (TNBC) is a type of breast cancer characterized by the absence of the three most common types of receptors in the cancer tumor known to fuel most breast cancer growthestrogen receptors (ER), progesterone receptors (PR) and the hormone epidermal growth factor receptor 2 (HER-2) gene.1TNBC cancer occurs in about 10 to 20 percent of diagnosed breast cancers and can be more aggressive and more likely to spread and recur.2,3Since the triple-negative tumor cells lack these receptors, common treatments for breast cancer such as hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective.4Currently, there are no targeted therapies approved to treat triple-negative breast cancer.5About Leronlimab (PRO 140)The U.S. Food and Drug Administration (FDA) has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for deadly diseases. The first as a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases including NASH. Leronlimab has successfully completed nine clinical trials in over 800 people, including meeting its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab can significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 plays an important role in tumor invasion and metastasis. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98 percent in a murine xenograft model. CytoDyn is therefore conducting aPhase 2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019. Additional research is being conducted with leronlimab in the setting of cancer and NASH with plans to conduct additionalclinical studies when appropriate.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation and may be important in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of graft-versus-host disease (GvHD).

About CytoDynCytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a key role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and in immune-mediated illnesses, such as graft-vs.-host disease (GvHD) and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in 2019 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab (PRO 140) as a once-weekly monotherapy for HIV-infected patients and, plans to initiate a registration-directed study of leronlimab monotherapy indication, which if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab (PRO 140) can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients, with some patients on leronlimab monotherapy remaining virally suppressed for more than four years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and has received clearance to initiate a clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at http://www.cytodyn.com.

Forward-Looking StatementsThis press releasecontains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i)the sufficiency of the Companys cash position, (ii)the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv)the Companys ability to enter into partnership or licensing arrangements with third parties, (v)the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi)the Companys ability to achieve approval of a marketable product, (vii)the design, implementation and conduct of the Companys clinical trials, (viii)the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix)the market for, and marketability of, any product that is approved, (x)the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi)regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii)general economic and business conditions, (xiii)changes in foreign, political, and social conditions, and (xiv)various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form10-K, and any risk factors or cautionary statements included in any subsequent Form10-Q or Form8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CONTACTS

Media:Grace FotiadesLifeSci Public Relationsgfotiades@lifescipublicrelations.com(646) 876-502

Investors: ir@cytodyn.com

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CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative...

Scientists Take Stem Cells and Convert Them to Heart Pacemaker Cells – Technology Networks

University of Houston associate professor of pharmacology Bradley McConnell is helping usher in a new age of cardiac pacemakers by using stem cells found in fat, converting them to heart cells, and reprogramming those to act as biologic pacemaker cells. He is reporting his work in theJournal of Molecular and Cellular Cardiology.

The new biologic pacemaker-like cell will be useful as an alternative treatment for conduction system disorders, cardiac repair after a heart attack and to bridge the limitations of the electronic pacemaker.

"We are reprogramming the cardiac progenitor cell and guiding it to become a conducting cell of the heart to conduct electrical current," said McConnell.

McConnell's collaborator, Robert J. Schwartz, Hugh Roy and Lillian Cranz Cullen Distinguished Professor of biology and biochemistry, previously reported work on turning the adipogenic mesenchymal stem cells, that reside in fat cells, into cardiac progenitor cells. Now those same cardiac progenitor cells are being programmed to keep hearts beating as a sinoatrial node (SAN), part of the electrical cardiac conduction system (CCS).

The SAN is the primary pacemaker of the heart, responsible for generating the electric impulse or beat. Native cardiac pacemaker cells are confined within the SAN, a small structure comprised of just a few thousand specialized pacemaker cells. Failure of the SAN or a block at any point in the CCS results in arrhythmias.

More than 600,000 electronic pacemakers are implanted in patients annually to help control abnormal heart rhythms. The small mechanical device is placed in the chest or abdomen and uses electrical pulses to prompt the heart to beat normally. In addition to having the device regularly examined by a physician, over time an electronic pacemaker can stop working properly.

"Batteries will die. Just look at your smartphone," said McConnell. "This biologic pacemaker is better able to adapt to the body and would not have to be maintained by a physician. It is not a foreign object. It would be able to grow with the body and become much more responsive to what the body is doing."

To convert the cardiac progenitor cells, McConnell infused the cells with a unique cocktail of three transcription factors and a plasma membrane channel protein to reprogram the heart cells in vitro.

"In our study, we observed that the SHOX2, HCN2, and TBX5 (SHT5) cocktail of transcription factors and channel protein reprogrammed the cells into pacemaker-like cells. The combination will facilitate the development of cell-based therapies for various cardiac conduction diseases," he reported.

Reference: Raghunathan et al. (2019).Conversion of human cardiac progenitor cells into cardiac pacemaker-like cells. Journal of Molecular and Cellular Cardiology. DOI: https://doi.org/10.1016/j.yjmcc.2019.09.015.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Scientists Take Stem Cells and Convert Them to Heart Pacemaker Cells - Technology Networks

5 Things to Know About Hair loss and Scalp Care Centre Papilla Haircare – Singapore Tatler

By Gerald Tan December 23, 2019 Tatler Focus

The centre offers the latest scalp innovations that address all your hair thinning woes by getting to the root cause

While you are pampering your skin with the most luxurious creams and lotions, dont forget to show your crowning glory some tender loving care, too. Beautiful tresses require plenty of effort and dedication to upkeep, but when you are faced with unfortunate scalp ailments or hair-loss issues, however, maintaining its volume and healthy shine can seem like anuphill task.

Enter hair loss and scalp care centre Papilla Haircare, which might have the solution for all your hair woes.

From state-of-the-art equipment to medicallybacked technologies, here are five things to know about the brand:

Thankfully, advances in science and technology can help alleviate many hairrelated problems. Papilla Haircare has the latest innovative solutions. Located at Ngee Ann City, it is a one-stop hub that utilises the latest medicallybacked technologies. The centre collaborates with doctors and scientists to concoct serums rich in stem cells in its own Korean laboratory to ensure the highest safety standards.

(Related: 7 Natural Beauty Products Your Skin Will Love You For)

Boasting sleek black and gold accents, Papilla Haircares contemporary interiors are a reflection of its cutting-edge services. Its clinically proven programmes are the result of extensive scientific research, meticulously developed by a group of Korean dermatologists and hair transplant surgeons. Thanks to their efficacies, these remedies have also been adopted for post-procedure use at top hair transplant centres in South Korea.

(Related: 5 Foods To Eat For Healthy Hair And Nails)

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5 Things to Know About Hair loss and Scalp Care Centre Papilla Haircare - Singapore Tatler

Answer ALS Project to Better Understand and Treat Disease Moves into New Phase – ALS News Today

Touted as the largestamyotrophic lateral sclerosis (ALS) investigative effort to date, the Answer ALS research program has finished an initial technology infrastructure stage and is ready to embark on its goal of finding more effective ALS treatmentsand, ideally, a cure.

A consortium of nearly two dozen medical research centers, technology companies, and 1,000 ALS patients, the program seeks to build the most comprehensive clinical, genetic, molecular, and biochemical assessment ever done into ALS. Results will be shared via secure links with the global research community.

Led byJohns Hopkins University and the Robert Packard Center for ALS Research, the program aims to answer questions about ALS and find new therapies through use of cloud computing, artificial intelligence (AI), and machine learning. The project entails creating up to 1,000 unique stem cell lines from ALS patients and healthy controls, modeling the disease on a large scale and across its many variations.

Built by Avanade and other tech firms, the expansive cloud-based research infrastructures feature is its ability to handle an unprecedented amount of data. As work progresses, the platform will permit Answer ALS to incorporate new data and emerging technologies.

Today we can interrogate cell function like never before, Emily Baxi, PhD, executive director of the Robert Packard Center for ALS Research, said in a press release. Answer ALS researchers are essentially building thousands of patient profiles constructed piece by piece from multiple sources of data.

Using the power of AI and machine learning to integrate and analyze these profiles, we hope Answer ALS will lay the groundwork for uncovering ALS patient subgroups and identify the most effective treatment strategies for each, Baxi added.

Key to the infrastructure is a data query engine Avanade developed as part of the companys Technology for Social Good initiative, aimed at non-profit organizations. The engine enables scientists to submit a complex research question and get a response within hours, rather than days or weeks.

Designed by Jeffrey Rothstein, MD, PhD, founder and director of the Robert Packard Center, Answer ALS grew from a collaboration among the center, institutions, and Team Gleason, an organization founded by former National Football League player Steve Gleason after his ALS diagnosis.

Gleason and Team Gleason hosted a summit in 2013 attended by scientists, patients, caregivers, and other ALS stakeholders. The idea was to devise a novel plan to defeat ALS. A year later, the result was Answer ALS, said to be the worlds largest single ALS research project.

If we truly want to have an impact on seemingly incurable diseases like ALS, Parkinsons, Alzheimers and dozens of others, large scale, coordinated and collaborative efforts aided by technology are the best way to rapidly move forward, said Gleason. We havent answered ALS yet, but we are closer than ever before. Our work with technology partners like Avanade is a big reason for that.

Avanades purpose is to make a genuine human impact, said Pam Maynard, Avanades CEO. And what better way to do that than to help Answer ALS search for treatments, or even a cure for ALS? Our Avanade team is excited an honored to work with this inspiring group of medical researchers, technology partners and patient participants.

This project is fully enrolled, with 1,000 ALS patients taking part. Updates on the Answer ALS project can be found here.

Mary M. Chapman began her professional career at United Press International, running both print and broadcast desks. She then became a Michigan correspondent for what is now Bloomberg BNA, where she mainly covered the automotive industry plus legal, tax and regulatory issues. A member of the Automotive Press Association and one of a relatively small number of women on the car beat, Chapman has discussed the automotive industry multiple times of National Public Radio, and in 2014 was selected as an honorary judge at the prestigious Cobble Beach Concours dElegance. She has written for numerous national outlets including Time, People, Al-Jazeera America, Fortune, Daily Beast, MSN.com, Newsweek, The Detroit News and Detroit Free Press. The winner of the Society of Professional Journalists award for outstanding reporting, Chapman has had dozens of articles in The New York Times, including two on the coveted front page. She has completed a manuscript about centenarian car enthusiast Margaret Dunning, titled Belle of the Concours.

Total Posts: 6

Ins holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Cincias e Tecnologias and Instituto Gulbenkian de Cincia. Ins currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.

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Answer ALS Project to Better Understand and Treat Disease Moves into New Phase - ALS News Today

BELINDA Trial Tests Earlier Use of Tisa-Cel in Aggressive B-Cell Non-Hodgkin Lymphoma – Cancer Therapy Advisor

A multicenter phase 3 trial began enrolling patients earlier this year to test the safety and efficacy of tisagenlecleucel (tisa-cel/Kymriah) as a second-line therapy for aggressive B-cell non-Hodgkin lymphoma (NHL).

Tisa-cel, an anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, has already been approved for use in patients who have relapsed after receiving 2 lines of therapy. But its possible that, if administered sooner across treatment regimens, CAR-T could help more patients avoid relapse. The new study on this topic, known as BELINDA, aims to answer that question.

The hypothesis is that CAR-T cells should improve upon progression-free survival as compared to standard of care, said Michael Bishop, MD, director of the hematopoietic stem cell transplantation program at the University of Chicago Medicine, Illinois, and one of the BELINDA coauthors. Dr Bishop presented the study protocol at the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019, in National Harbor, Maryland.1

Around a third of patients with non-Hodgkin lymphoma (NHL) will relapse after receiving first-line immunochemotherapy, and another 10% to 15% do not respond to initial treatment. For these patients, the outlook is grim: median overall survival is less than 12 months. Second-line treatment consists of high-dose chemotherapy combined with autologous stem cell transplant, but fewer than half of patients will qualify for a transplant. Youve got half the patients who wont get the transplant, and the other half that do, only a quarter of those will have sustained remission, said Dr Bishop. Its a large unmet patient need.

Dr Bishop went on to explain that previous trials have indicated that some 30% to 40% of patients receiving CAR-T therapy for multiply relapsed or refractory NHL have achieved long-term remission. The other exciting thing about this trial is its moving CAR-T up the treatment algorithm, he said.

The BELINDA trial is a multicenter, phase 3, open-label trial, in which patients are randomly selected to receive treatment in 1 of 2 arms: tisa-cel, or standard of care. Similar to the ZUMA-7 trial,2 which tested another CAR-T therapy called axicabtagene ciloleucel (Yescarta), BELINDA is enrolling patients whose disease either does not respond to first-line therapy (rituximab and anthracycline) or has returned within 12 months, and who are eligible for autologous stem cell transplant.

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BELINDA Trial Tests Earlier Use of Tisa-Cel in Aggressive B-Cell Non-Hodgkin Lymphoma - Cancer Therapy Advisor

‘With six weeks in isolation for leukaemia treatment, what you really need is someone to give you a good laugh’ – Telegraph.co.uk

Patients are very isolated. The staff nurses on the ward will obviously go and see the patient, but youve got long periods of time on your own. It is easy to imagine that, with the chaos of the Christmas period, the loneliness for inpatients will grow even more intense.

And that loneliness is frightening for patients, says Smith: When youre there, in isolation for six weeks, your mind whirrs. Your relatives can come, but only if they have no coughsor colds or diseases. They dont want to come if theyre going to makeyou poorly. But Shirley comes in once a week and talks to me, he says, with a chuckle.

Emmerson explains: I work with the nurses, and they tell me whos where, and who they think would like a visit, or if theres anything I can do. And then, I just go along and introduce myself. Thats how I met Steve. Yes, it was during my first blast of chemo, in May, Smith begins, and Emmerson adds, smiling: Ive been there all the way through.

This consistent support has been invaluable to Smith, who recalls sitting alone in his room, wondering whether the chemotherapy was working, and what would happen next. It does play with your head, he acknowledges, as you sit by yourself, thinking: whats going on? A typical Thursday when Smith is an inpatient goes like this: he wakes and has breakfast between 8-9am (I try to get a full English out of it, he jokes, though he soberly acknowledges that the treatment makes most patients lose their appetite.)

Then he might watch some television and await Emmersons visit at about 10.30am. From day one, Shirley would always laugh with me, he explains. Shirley would say, Have you thought about this or Have you tried that but what I really got out of it was having someone to sit and talk to about my family, about her family. Its just a giggle, but that laughter makes you feel better. Emmerson would stay until around lunchtime.

In the afternoons, Emmerson heads to the bright haematology outpatient ward, which sees 500 patients each week. Here, the waiting room has a side room with a collection of row after row of pamphlets from Macmillan and other charities.

In a voice inaudible to the dozen or so waiting patients, with their accompanying family members, Chatten explains that the room used to be closed off, but a bereaved family donated money so it could be spruced up and opened to the waiting room, so the range of available help would be easily discoverable.

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'With six weeks in isolation for leukaemia treatment, what you really need is someone to give you a good laugh' - Telegraph.co.uk

Merck’s KEYTRUDA (pembrolizumab) Approved in Japan for Three New First-Line Indications Across Advanced Renal Cell Carcinoma (RCC) and Recurrent or…

Advanced renal cell carcinoma and head and neck cancer have historically been associated with poor outcomes and new treatment options are needed in Japan, said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. Todays approval of three new first-line KEYTRUDA regimens represents a significant milestone for patients diagnosed with these aggressive forms of cancer and will provide patients in Japan with important alternatives to standard therapies.

The approval for KEYTRUDA in combination with axitinib for radically unresectable or metastatic RCC is based on results from the KEYNOTE-426 trial, in which KEYTRUDA in combination with axitinib demonstrated statistically significant improvements in the dual primary endpoints of overall survival (OS) (HR=0.53 [95% CI, 0.38-0.74]; p=0.00005) and progression-free survival (PFS) (HR=0.69 [95% CI, 0.56-0.84]; p=0.00012) compared to sunitinib monotherapy.

The approval for KEYTRUDA for the first-line treatment of patients with recurrent or distant metastatic head and neck cancer is based on results from the Phase 3 KEYNOTE-048 trial which evaluated KEYTRUDA in combination with platinum and 5-fluorouracil (5-FU), or KEYTRUDA monotherapy compared with standard treatment (cetuximab in combination with platinum and 5-FU), as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma. In the trial, KEYTRUDA in combination with platinum and 5-FU significantly prolonged OS (HR=0.77 [95% CI, 0.63-0.93]; p=0.00335) compared with standard treatment. As monotherapy, KEYTRUDA demonstrated non-inferiority (HR=0.85 [95% CI, 0.71-1.03]; p=0.00014) compared with standard treatment. Additionally, KEYTRUDA monotherapy demonstrated a statistically significant improvement in OS in patients whose tumors expressed PD-L1 (CPS 1) compared with standard treatment.

Last year, an estimated 850,000 new cancer diagnoses were made in Japan alone, underscoring the critical need for innovative research and development to identify additional treatment options, said Jannie Oosthuizen, managing director of MSD in Japan. The new approvals of KEYTRUDA in advanced renal cell carcinoma and head and neck cancer build on previous approvals in melanoma, advanced non-small cell lung cancer and advanced MSI-H cancers, allowing us to bring KEYTRUDA to even more patients in Japan.

Renal cell carcinoma is by far the most common type of kidney cancer, with approximately 403,000 cases of kidney cancer diagnosed worldwide in 2018 and about 175,000 deaths from the disease. In Japan, it is estimated there were more than 24,000 people diagnosed with kidney cancer, and more than 8,000 deaths occurred in 2018.

Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. It is estimated that there were more than 705,000 new cases of head and neck cancer diagnosed and over 358,000 deaths from the disease worldwide in 2018. In Japan, it is estimated that more than 22,000 new cases of head and neck cancer were diagnosed, and more than 8,000 deaths occurred in 2018.

About KEYTRUDA (pembrolizumab) Injection

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,000 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected Indications for KEYTRUDA (pembrolizumab) in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 34) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

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Merck's KEYTRUDA (pembrolizumab) Approved in Japan for Three New First-Line Indications Across Advanced Renal Cell Carcinoma (RCC) and Recurrent or...

Rett Syndrome Therapies are Focus of Stemonix-Atomwise Partnership – Rett Syndrome News

StemoniX and Atomwise will work together to discover and develop small molecules that could be potential new therapies for people with Rett syndrome.

This collaboration will take advantage of StemoniXs human microOrgan platform and combines it with Atomwises artificial intelligence technology to expedite the development process and increase the chances of clinical success of new therapeutic molecules.

The joint venture brings together the complementary technologies of StemoniX and Atomwise, creating an opportunity to go from model to molecule to validated drug in a fraction of the time and cost required with traditional methods, Ping Yeh, co-founder and CEO of StemoniX, said in a press release.

Atomwise is a great partner for a notoriously challenging disease area. Their expertise will enable drug discovery on historically undruggable targets and provide new opportunities for treating rare neurological diseases, he added.

Researchers at StemoniX use human induced pluripotent stem cells (iPSCs) to build ready-to-use functional tissues that mimic the biological responses of human organs. iPSCs are developed by reprogramming cells to revert to an embryonic-like state which are then able to differentiate into all cell types.

With the companys microOrgan platform, researchers have used iPSCs collected from patients with Rett syndrome to build 3D microbrains made of nerve cells and astrocytes (cells that support neurons, respond to injury, and regulate blood flow and inflammation in the brain). Such microbrains recapitulate features of the disease.

This platform could provide greater accuracy and consistency to clinical trials, according to the company.

In turn, Atomwises artificial intelligence technology uses statistical approaches that were designed to overcome limitations of current preclinical treatment discovery and development methods.

It combines information from millions of measurements and thousands of protein structures to predict the binding of small molecules to protein targets. This approach makes it possible to pursue a comprehensive therapy discovery with unparalleled precision and accuracy, according to Atomwise.

New technologies and approaches are vital to address the needs of patients, saidAbraham Heifets, PhD, co-founder and CEO of Atomwise. StemoniX has made remarkable progress with their microBrain 3D platform and its application to Rett syndrome. It is a potentially powerful tool to rapidly evaluate compound efficacy and assess their suitability for clinical trials, and we are excited to partner with them.

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Rett Syndrome Therapies are Focus of Stemonix-Atomwise Partnership - Rett Syndrome News

Pike River widow ‘on the up’ after stem cell treatment for cancer – Stuff.co.nz

Pike River widow Anna Osborne is "on the up" and out of hospital in time for Christmas.

Osborne, whose husband Milton died in the 2010 Pike River mine disaster, had stem-cell treatment for Hodgkinlymphoma in October.

She had been told she only had a month to a year to live without it.

Phil Walter/Getty

Anna Osborne, from the Pike River Family Reference Group, embraces Prime Minister Jacinda Ardern at the mine entrance earlier this year.

Friend and Pike River mother SonyaRockhouse said Osborne's treatment went well, but there was still a long road ahead.

READ MORE:*Pike River mine tunnel entry an important moment for widow*Pike River re-entry team breaks through into mine drift*Pike River widow 'full of nerves' for mine drift re-entry*The road to getting back into Pike River

"I think the treatment is working for now. She just got her bloods done and they were good and they are the most important thing," she said.

Kevin Stent/Stuff

Osborne and Sonya Rockhouse at the announcement the Government would re-enter the Pike River mine.

Osbornewasdiagnosed with Hodgkinlymphoma in 2002 when she was 36.

She had radiation for six weeks and went into remission, but the cancercame back just before the Pike River tragedy in November 2010, when 29 men where killed in a series of explosions at the coal mine. Osborne helped campaign for thelegalisation of medicinal cannabiswhile undergoing chemotherapy in 2015.

Her stem-cells wereharvested and frozenin August. The stem cell transplanttook place in Christchurch in October aftersix days of intensive chemotherapy.

JOANNE CARROLL/Stuff

Anna Osborne, pictured during treatment for Hodgkins lymphoma in 2016.

The treatment had its own risks.

Osborne was in isolation for five weeks but after shereturned home, she hadsome set backs and small complications,Rockhousesaid.

"She was so crook. She lost a lot of weight. She's had two or three trips to hospital since then," she said.

Supplied/Pike River Recovery Agency

Mine worker Bryan Heslip offers a hand to Osborne and Rockhouse after entering the Pike River mine drift during the re-entry operation.

"She's on the up now,but [there is] still a long way to go. She's at home and is getting some colour back in her cheeks, [and is] starting to look like her old self."

Rockhouse said Osborne was focusing on her recovery and hoped to be able to go to the Pike River mine for the next milestone, which was removing the 170m seal expected to take place in January.

Continued here:
Pike River widow 'on the up' after stem cell treatment for cancer - Stuff.co.nz