Daily Archives: November 19, 2021

Visiongain has published a new report on Alternative Medicines and Therapy Market Report to 2031: Forecasts By Intervention (Botanicals (Ayurveda, Naturopathy, and Homeopathy), Acupuncture, Mind & Body Healing (Yoga, Meditation, Energy Healing, Eden Energy Medicine, and Others), Chakra Healing, Hypnotherapy, Kinesiology, Magnetic Intervention (Magnetic Resonance Therapy and Bio-magnetic Therapy), By Distribution Channel (Hospital, Special Clinics/Centers, Direct Contact, E-training, and Others) PLUS COVID-19 Recovery Scenarios.

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COVID-19 Impact on Alternative Medicines and Therapy Market

With travel constraints and isolation requirements in place across the world, most of the alternative therapy providers haven't had any chance to carry out therapy sessions. The industry has had to adjust to a new environment with the growing use of the internet and social media due to social distancing the chances of any profit is very less. Visiongain has anticipated the impact of COVID-19 lockdown on the market value of global leaders, followers, and disrupters. As lockdown has been executed differently across the world, the impact of the unplanned lockdown is also different in the countries. This report will help to develop strategies for companies by region/countries.

Market Drivers

Government Initiatives and Changing the Regulatory Scenario

Government initiatives play an essential role in improving the acceptance of alternative medicine and therapy. Also, rising funding, forming government services keen on alternative therapies, and the costly nature of alternative treatment opportunities is encouraging key players to spend in the market for alternative medicine and therapy.

Regional government bodies and key players operating in the market are more focused on strengthening health tourism related to alternative medicine and therapy. Government bodies in India are greatly financing the progress and standardization of facilities of alternative medicine and therapy in the past few years. For example, "Ministry of Ayush" is launched by national authorities to manage research, education, development, and other facilities of yoga, homeopathy, Ayurveda, and naturopathy.

Growing Prevalence of Stress-related Diseases

Rising incidence and prevalence of Polycystic Ovary Disease (PCOD), hypothyroidism, lupus, acute stress disorder, and hypopituitarism required special therapy such as meditation, acupuncture, Ayurveda, naturopathy, aromatherapy, nutritional therapy, and others are expected to be major driving factors for the growth of the alternative medicines and therapy market during the forecast period. Also, as per the Centers for Disease Control and Prevention (CDC), nearly 1.70 million people die from a chronic disease every year in the USA. Although chronic diseases are the major reason for death for men and women alike because women face unique health issues. Around 37% of women suffer from chronic diseases, compared to 30% of men. Thereby, the rising high prevalence of Polycystic Ovary Disease (PCOD) and other chronic disorders leads to weight gain and other complications. In turn, it is projected to attain substantial growth for the alternative medicines and therapy market in the given time frame.

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Market Opportunities

Growing Awareness and Acceptance of Alternative Medicine

The growing acceptance of alternative medicines and natural therapies, hi-tech advancement, growth in geriatric people, ease to reach, growing healthcare spending, government initiatives, and growth in acceptance of alternative medicines and therapies are likely to push the market for alternative medicines and therapies during the forecast period. Also, rising consumer expenditure in healthcare, growth in the number of prevalence of several illnesses, and price-effectiveness of alternative medicines and therapies are likely to fuel the alternative medicines and therapies market growth.

Rising demographics and markets in emerging countries such as China and India are expected to dominate the global alternative medicines and therapies market growth in Asia. Furthermore, the growing demand for herbal medicines and a growth in demand for alternative drugs and therapies are projected to offer opportunities to the target industry.

Competitive Landscape

Key players operating in the global alternative medicines and therapy market are AYUSH Ayurvedic Pte Ltd, Columbia Nutritional, Ramamani Iyengar Memorial Yoga Institute, John Schumacher Unity Woods Yoga Centre, Nordic Nutraceuticals, Herb Pharm, Pure Encapsulations, LLC., The Healing Company Ltd, and Sheng Chang Pharmaceutical Company.

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Information found nowhere elseWith this new and exclusive report, you are less likely to fall behind in knowledge or miss out on opportunities. See how our work could benefit your investment, research, analyses, and decisions. Visiongain's study is for everybody needing commercial analyses for the Alternative Medicines and Therapy Market and Leading Companies. You will get the most recent data, opportunities, trends, and predictions.

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Visiongain is one of the fastest growing and most innovative, independent, market intelligence around, the company publishes hundreds ofmarket research reportswhich it adds to its extensive portfolio each year. These reports offer in-depth analysis across 18 industries worldwide. The reports cover a 10-year forecast, are hundreds of pages long, with in depth market analysis and valuable competitive intelligence data. Visiongain works across a range of vertical markets, which currently can influence one another, these markets include automotive, aviation, chemicals, cyber, defense, energy, food & drink, materials, packaging, pharmaceutical and utilities sectors. Our customized and syndicated market research reports means that you can have a bespoke piece of market intelligence customized to your very own business needs.

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Alternative Medicines and Therapy Market Report Up to 2031: Visiongain Research Inc - Benzinga - Benzinga

Single-center study finds similar risks for PGD-3 with both

In patients undergoing lung transplantation, risks for severe/grade 3 primary graft dysfunction (PGD-3) were similar whether patients were treated with inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO). Thus, researchers concluded, iEPO may be a viable option in the treatment of these patients.

They published their results in JAMA Surgery.

Inhaled nitric oxide (iNO) is administered after lung transplant (LT) to promote lung-allograft function by improving oxygenation and lowering pulmonary vascular resistance. Consequently, iNO may help mitigate development of severe (grade 3) primary graft dysfunction (PGD-3), which is diagnosed within 72 hours after LT and is strongly associated with short- and long-term mortality. Although iNO is not approved by the U.S. Food and Drug Administration for this indication, international guidelines support its use after LT, explained Kamrouz Ghadimi, MD, MHSc, of Duke University School of Medicine, Durham, North Carolina, and colleagues.

They added that iNO is roughly seven times more expensive than iEPO, and annual costs exceed millions of dollars nationwide, a disadvantage that has brought iEPO forward as a cost-saving alternative, despite a lack of robust evidence or comparisons with iNO.

In an interview with BreakingMED, Ghadimi explained the basis of their trial.

The study started out as a quality initiative in 2014-2015 at Duke University Hospital. We were charged with the question of evaluating our bottom-line use in the cardiothoracic ICUs regarding inhaled pulmonary vasodilator usage as an adjunct for the medical management of patients undergoing cardiothoracic surgery. Importantly, the patient service line that uses these medications most commonly in our cardiothoracic ICU are those who undergo lung transplantation as well as those that undergo advanced heart failure operations such as left ventricular assist devices or heart transplantation, he said.

We wanted to better evaluate these patients, if indeed we could utilize an alternative medication to the solitary inhaled vasodilator nitric oxide; if we could do this safely; if we could develop protocols; if all the stakeholders would be on board, including respiratory therapy, clinicians, other staff physicians surrounding the care of these patients were in agreement; and how we could best implement and deliver the medication, Ghadimi added.

In this independent analysis of patients from the Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes (INSPIRE-FLO) trial, Ghadimi and colleagues enrolled 201 patients (median age: 64 years; 64.2% men) with end-stage lung disease who underwent single (13.9%) or bilateral lung transplantation (86.1%). They grouped patients into five strata based on prognostic clinical features and then randomized patients per stratum to treatment with either iNO or iEPO at the time of lung transplantation.

The most common reason for lung transplantation was restrictive lung disease (62.7%), followed by obstructive disease (20.9%).

These are very vulnerable patients. They entrust our program, our clinicians, and our staff and coordinators. We didnt want to take this initiative lightly as we changed practice or implemented a new medication in this population, noted Ghadimi.

The median duration of time from randomization to treatment was five days, and the treatment durations were similar between the two treatment groups (45.7 hours in the iNO group versus 46.6 hours in the iEPO group), as were allogeneic packed red blood cell transfusion and ECMO support. Delayed chest closure occurred in 15.3% and 6.8%, respectively (P=0.530).

Treatment with both agents was initiated in the operating room before lung allograft reperfusion and administered continuously until cessation criteria met in the intensive care unit, explained Ghadimi et al. In the intention-to-treat population, 103 patients were treated with iEPO and 98 with iNO.

The primary outcomePGD-3 at 24, 48, or 72 hours after lung transplantationoccurred in 44.7% of patients treated with iEPO, compared with 39.8% of those treated with iNO (risk difference: 4.9%; TOST 90% CI: 6.4% to 16.2%: P=0.02 for equivalence). At 48 or 72 hours, these incidence rates were 28.2% and 26.5%, respectively (risk difference: 1.6%; 90% CI: 8.8% to 12.0% for equivalence); and at 72 hours, the rates were 16.3% versus 21.3% (risk difference: 5.0%; 90% CI: 4.5% to 14.6% for equivalence).Researchers found no between-group differences in secondary outcomes, which included duration of mechanical ventilation, hospital and ICU length of stay, incidence and severity of acute kidney injury, postoperative tracheostomy placement, and mortality rates in hospital and at 30 and 90 days.

In their accompanying editorial, Ankit Bharat, MD, of Northwestern University Feinberg School of Medicine, Chicago, and fellow editorialists wrote: The present study by Ghadimi et al lacks a control arm that did not receive any pulmonary vasodilators, allegedly owing to their institutional practices. Hence, it remains unclear whether either iNO or inhaled epoprostenol conferred any benefit and whether their use should be supported in routine prophylaxis against PGD. On the contrary, the seemingly higher rates of PGD might support that pulmonary vasodilators can paradoxically worsen allograft edema and increase PGD scores, they wrote.

Ghadimi explained that at Duke University, they now use iEPO as an alternative to iNO based on these results, but he offered an important caveat.

Other centers should consider the use of iEPO as an alternative to iNO based upon how they utilize the medications in their own centers. Thats important because how we utilize these medications might be different between centers, he told BreakingMED. At our center, we prophylactically put all patients on this medication. Other centers prefer to use the medication if its indicated, if theres a reason to suspect that there is a problem with the lung graft, and thats when they initiate it.

We use it in a certain way. I certainly encourage readers to look at our protocols (which are in the supplements) and take a deep dive and see how our approach fits in with theirs. I think theres a lot of opportunity here for multicenter collaborations, Ghadimi concluded.

Limitations of the study include its single-center design that was not placebo controlled, moderate size, and power, and short duration; the use of a prespecified equivalence margin based on an incidence range that may be too large; and the use of a stepwise, data-drive, model-building approach rather than a prespecified adjustment model due to the complexity of risk factors in these patients.

In this single-center study, researchers found that rates of severe/grade 3 primary graft dysfunction (PGD-3) after lung transplantation were similar between patients treated with inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO).

Be aware that this study investigated off-label use of both iEPO and iNO.

Liz Meszaros, Deputy Managing Editor, BreakingMED

This study was supported by the Duke University Health System.

Ghadimi reported receiving grant support from the National Institutes of Health, Duke Health, and the International Anesthesia Research SocietyMentored Research Training program.

Bharat reported no conflicts of interest.

Cat ID: 633

Topic ID: 630,633,570,633,730,192,195,925,159,312,492

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Inhaled Epoprostenol May Be An Alternative to Inhaled Nitric Oxide After Lung Transplantation - Physician's Weekly

ANN ARBOR, MI Linda Diane Feldt, a longtime Ann Arbor pedestrian safety and cycling advocate and holistic health practitioner, has died.

She was 62.

City officials, friends and many who knew her as a friendly face and force around town are sharing remembrances of the Keppler Court resident who wore many hats, including chairing the citys Transportation Commission.

She was a resident advocate of the highest order, a person who saw a leadership/policy gap in our community and was able to effect systemic change, Mayor Christopher Taylor said in a statement. She organized tirelessly with others to initiate and work the Pedestrian Safety Task Force, envision and implement the Transportation Commission, and was the plain and obvious choice to chair both. If you walk or cycle in Ann Arbor, you owe her no small measure of your safety and your full thanks.

Feldt exemplified kindness, action and care for others, Taylor said, expressing condolences to her family and loved ones.

She will be truly missed by all who had the good fortune to know her, he said.

An Ann Arbor native and 1976 graduate of Community High School, Feldt began studying holistic health care during her high school days and studied anthropology and sociology at the University of Michigan. She was a program coordinator at Ozone House before becoming a holistic health practitioner and taught health classes at Rudolf Steiner School and UM.

She was a board member for various organizations, including three terms as president of the Peoples Food Co-Op, volunteered as a crisis counselor and trainer, and worked in the field on environmental projects, including as a volunteer with the Huron River Watershed Council.

She also was a community blogger for AnnArbor.com, writing about foraging, wild foods and herbal medicine.

Her website, LindaDianeFeldt.com, features six publications she wrote over the years, including Wildcrafting Recipes: Loving and Eating Wild Foods and Spinach and Beyond: Loving Life and Dark Green Leafy Vegetables. She was once called the doyenne of alternative healing by the Ann Arbor Observer and a notable in the field by Massage Magazine.

Feldt, who was open about her battle with health issues in recent years, including heart problems, died Wednesday night, Nov. 17. She is survived by her husband, Richard Conto.

She was so desperately sick for so long, said Patricia Anderson, a friend who said Feldt was clinically diagnosed with long COVID based on her symptoms last year.

Anderson, who got to know Feldt several years ago through the A2B3 (Ann Arbor Bi Bim Bop) lunch group, said she and Feldt swapped tips and tricks about herbal remedies and she took one of Feldts workshops. After seeing the outpouring of remembrances on social media, shes realizing Feldt meant a lot to many people.

She was just so special to so many people and she had so much influence on our town, Anderson said. She was really one of those people who really put into practice think globally, act locally. I mean, she lived it.

Through her transportation advocacy, Feldt pushed for a fundamental shift in the citys car culture, calling for lowering speeds on streets, getting more people commuting without using cars and updating pedestrian and cycling infrastructure and laws.

Studies show that even when you slow down cars, it doesnt add much to the travel time, and most of us will agree thats worth saving a life or two or more, Feldt said when she spoke at a forum at the downtown library in February 2020.

Conto said he and Feldt married late in life, so he didnt get to see all of her accomplishments as they happened.

But her accomplishments were enormous for the community and for the individual, he said, adding she helped start Ozone House and was involved in managing it as a teenager. Shes been involved in physical therapy and helping people heal almost her whole life, from high school at Community High until just days before she died when she saw babies and helped them recover from the trauma of birth.

Her father was a UM urban planning professor and her mother was a research scientist and Feldt combined what she learned from both, Conto said. And while she never had children of her own, she had several dogs over the years and particularly loved Rhodesian Ridgebacks.

Up until the very end, she was looking to improve the world by integrating all of her skills, Conto said.

She wanted to improve the diagnosis of heart disease, of heart attacks in women, because what she saw ... pointed out how poorly women are diagnosed, he said. That was a project she was working on even as she was suffering heart attacks herself.

Anderson said Feldt was at last weeks A2B3 virtual meetup despite having just gotten out of the cardiac hospital.

We were chatting and stuff and she sort of inserted herself into the conversation. She goes, Well, I win the award for the most devoted attendee of A2B3, " Anderson recalled.

We were all like, We are not going to argue with you on that one. You do, you win. And she was saying, I just really wanted to be here and it just mattered so much to me to be here and its just so great to see you guys. "

Anderson said Feldt had a common phase she left with the group: Take nothing for granted.

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We have not done enough. Ann Arbor tax to fight climate change headed to vote

Ann Arbor may take 20 years to replace old water lines to mitigate lead risks

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Ann Arbors Linda Diane Feldt remembered as resident advocate of the highest order - mlive.com

FLINT, Mich., Nov. 18, 2021 /PRNewswire/ -- Forum Health, LLC, nationwide network of integrative and functional medicine providers, has acquired the practice of Jane Kennedy, CFNP, MN, MPH located in Santa Rosa, CA.

Jane Kennedyhas been in clinical practice for over 30 years with a focus on disease prevention and helping patients regain their vitality after experiencing hormone imbalances with bio-identical hormone replacement therapy.

"We are excited to welcome Jane Kennedy and her team to Forum Health," said Adam Puttkammer, president of Forum Health. "Her expertise in the field of integrative medicine has made her a leading hormonal health practitioner in Northern California."

In addition to treating hormone imbalances, Jane Kennedy's practice also helps promote optimal health for men and women through thyroid therapy, adrenal and metabolic support, medical weight loss, neurotransmitter balance, gut health and detox, inflammation, PMS and postpartum, healthy lifestyle practices and disease prevention.

"I'm thrilled to join the Forum Health network," said Jane Kennedy. "Their philosophy of restoring the natural balance of the mind, body and spirit with the most effective treatments and least side effects is exactly what our clinic practices every day. And by joining Forum Health, my patients will continue to receive the same high quality of care into the future with even more expanded services."

"Jane Kennedy and her team embody everything we look for in a Forum Health practice," said Phil Hagerman, CEO of Forum Health. "Their commitment to providing healthy hormone solutions and alternative treatments for men and women supports Forum Health's mission to redefine healthcare and partner with patients on their journey to a healthy and vibrant life."

For more on Forum Health and how to become a practitioner, visit http://www.forumhealth.com.

About Forum Health, LLC

Forum Health, LLC is a nationwide provider of personalized healthcare. Steeped in the powerful principles of functional and integrative medicine, Forum Health providers take a root-cause approach to care. They listen and dig deep exploring lifestyle, environment, and genetics to help each patient achieve their ultimate health goals. Members have access to advanced medical treatments and technology, with care plans informed by data analytics and collaborative relationships. To learn more, visit forumhealth.com.

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Forum Health Welcomes Santa Rosa Hormone Functional Medicine Clinic as its Third Location in California - Iosco County News Herald

The EU has a role to play in regulating the use of off-label medicines, says Cyrus Engerer

The COVID-19 pandemic has shown us how important coordination among countries is when responding to health threats. It also revealed the crucial role the EU can play in promoting joint health responses that fully respect each Member States role in governing their health systems.

During the pandemic we saw that the most promising vaccine candidates, which played a key role in our pandemic response, were developed and produced in Europe. We can all be proud, as Europeans, of the existing legal framework for pharmaceuticals, which rewards innovation and ensures new medicines are proven safe and effective before they make it to patients.

We must credit this regulatory system above all with delivering us the most effective COVID-19 vaccines, and in the coming years the EU must strive to remain the world leader in health policy, by setting high standards and criteria for quality and safety. With the Pharmaceutical Strategy for Europe, we will do just that. We will also seek to ensure that patients can benefit from future innovative health technologies by making sure the regulatory system remains fit-for-purpose and that Europe remains an attractive place to research and develop new pharmaceutical products.

The COVID-19 pandemic, however, also illustrated that increased regulatory flexibility and innovative approaches for the development and approval of medicines is sometimes needed. When Europe was scrambling for a possible COVID-19 treatment there was, for example, a growing call for identifying the effectiveness of existing drugs for treating COVID-19, a practice called repurposing. In October, the European Medicines Agency launched Repurposing of authorised medicines: pilot to support not-for-profit organisations and academia, a project which forms part of the Pharmaceutical Strategy which aims to support the repurposing of existing medicines for a wide range of disease areas.

EU patients should receive the same access to safe and effective treatments, irrespective of where in the Union they live

However, despite this robust EU system of approval, medicines are routinely used that are not approved, this is called off-label use (meaning that the medicine is not used for their approved indication or method). It is a legal and mostly necessary practice in many disease areas, where there are currently no suitable approved alternatives available. This means physicians are left to determine, at their own discretion, whether an individual patient will have greater medical benefit from an off-label alternative drug.

However, some authorities take advantage of the existence of this prescriber freedom to promote off-label use at a wide scale, aimed at driving down health care costs. This is unacceptable since it increases the risk for patients that would otherwise have received an approved and safe alternative and undermines the EU regulatory system for approval of medicines.

EU patients should receive the same access to safe and effective treatments, irrespective of where in the Union they live. We should therefore use the opportunity of the Pharmaceutical Strategy, and the ongoing discussions around the EUs role in health policy following the COVID-19 pandemic, to consider how we can formulate a common approach to off-label use that ensures it is done safely and is limited to where it is strictly medically necessary.

There are serious safety concerns with large-scale off-label use of medicines, says the European Brain Councils Frdric Destrebecq. This is why we have come together with other Brussels health stakeholders to propose common European guidelines for when and how off-label prescription should take place.

Many people are aware of the tragedy of thalidomide and its use by pregnant women in the 1950s, an event that prompted governments in Europe to significantly change the approval process for medicines. The very strict licensing process for medicines that exists in Europe today, now centred around the European Medicines Agency, was created after the thalidomide tragedy. While there are still rare issues with authorised medicines in Europe, in general it has proved to be a very robust and rigorous system, focused above all on the safety of patients who are taking medicines.

However, gradually this system is being bypassed, bringing real risks to patients in Europe. Just in May last year, EURACTIV reportedthat the practice of using medicines off-label to induce labour in pregnant women had led to severe health implications and even death. There is always a varying chance of adverse reactions if and when people are prescribed medicines not approved for that particular use a practice which is commonly referred to as using medicines off-label.

Doctors are free to prescribe the use of a medicine off-label, when there is no good alternative medicine, and the doctor believes the possible benefit to the patient outweighs the safety risk. This happens in many disease areas, including oncology, psychiatry, paediatrics and rare disease, to name a few.

Everyone agrees that this concept of "off-label use is positive, since it is based on a patients individual medical need and on the trust placed in doctors to make the best decision for their patients. An important part of this exception is the discussion between doctor and patient it is the responsibility of the doctor that the patient is fully aware that the medicine is off-label, and understands the risks involved.

In most cases patients are not adequately informed about what is happening, nor being told about the risks involved, and are therefore exposed unnecessarily to increased risks of adverse events

However, off-label use is now increasingly being used in health systems to save money, with off-label medicines deliberately being given to patients when there are already approved medicines available. And in most cases patients are not adequately informed about what is happening, nor being told about the risks involved, and are therefore exposed unnecessarily to increased risks of adverse events.

In response to these troubling developments, together with other European health stakeholders, we call for a Good Off-Label Use Practice, a blueprint for a clear, European-wide framework to ensure patients safety and help healthcare professionals make more informed decisions when prescribing medicines off-label". The Practice states that off-label should only be used when a qualified health care professional finds that there is a clear medical need; if there are no other on-label treatments available or authorised treatments have failed, if there is scientific evidence in the literature that supports the use, ifpatients are adequately informed of the possible risks and benefits of the medicines, and the results must be reported by the healthcare professional in the patient file and also by patients themselves.

You are invited to join us on 30 November, between 2:30 4 pm (CET) for a discussion among patients, clinicians and policymakers about how we can ensure greater awareness of the use of medicines off-label through the exchange of ideas and best practices from different European countries.

REGISTER

This content was commissioned by Good Off-Label Use Practice (GOLUP) and produced by Dods

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A harmonised EU approach to the off-label use of medicines? - The Parliament Magazine

VANCOUVER, BC, Nov. 18, 2021 /PRNewswire/ --Advances in the collective genetic understanding of diseases, and the ability to identify disease biomarkers, is ushering in a new era of personalized medicine. Technologies such as CRISPR/Cas9 are also paving the way for improved, more tailored treatments targeted to a specific genetic marker of a disease. As our understanding of the molecular underpinnings of disease continue to improve, so, too, will the technologies at our disposal to treat them.

We've already seen the benefits of this type of personalized medicine in the cancer realm. Using a person's (or disease's) genes to drive cancer therapy is known as precision medicine. Precision medicine can help doctors identify high-risk cancer patients, choose treatment options, and evaluate treatment effectiveness. Precision medicine can also be used to prevent certain types of cancer, diagnose certain types of cancers early (leading to earlier treatment and better outcomes), and diagnose specific types of cancer more correctly.

As targeted therapies continue to advance, we will continue to see their impacts flow beyond that of the cancer realm. One area in which interest is ramping up is neurodegenerative diseases, which are chronic, progressive diseases affecting the brain and its constituent cells. Neurologic disease can be genetic, or caused by a stroke or brain tumor. Examples of neurodegenerative disease include Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease. These diseases have a genetic component, with specific genes playing a role in the development and progression of disease, especially in rare forms. Neurodegenerative conditions, like cancer, are devastating and costly. Collectively, neurodegenerative conditions cost people in the United States $655 billion in 2020.

Can we apply concepts from targeted therapies developed for cancer to create better outcomes for patients suffering from neurodegenerative diseases? What's more, can precision medicine be used to treat other large unmet needs in the field of neurology, such as neuropsychiatry, pain, epilepsy, sleep disorders, and stroke?

Precision medicine in neuroscience and neurology is where many companies have dedicated their time and efforts. Three companies trading on the NASDAQ in this space that investors should research are Alnylam, Ionis Pharmaceuticals, and Regeneron.

Neuroscience research companies are clamoring to make use of the plethora of cellular and molecular biology data that is emerging about drugs and the patients who use them. There is much more information to be gleaned from diseases and patients than the genetics, which may not reveal information about the ways that genes are formally transcribed and expressed. Emerging technologies, therefore, also look at the RNA profiles of a drug response, patient, or disease state, called transcriptomics; and the set of proteins expressed by a cell, tissue, or organism, called proteomics. While a challenge with gene therapy is reimbursement by insurance providers, research is underway that can make gene therapies more common, and pave the way for more established insurance structures.

RNA targeting is an active area of research for neurodegenerative disease, with companies such as Skyhawk Therapeutics, Regeneron Pharmaceuticals, Alnylam Pharmaceuticals, and Takeda involved. By modifying genetic transcription via RNA technologies, these companies hope to develop novel treatments for disorders of the central nervous system. The study of RNA profiles in a given cell, tissue, or organism is known as transcriptomics, and this area will likely heat up as these researchers work to develop pioneering RNA technologies to target neurodegenerative disease.

Proteomics, or the study of the proteins expressed by a cell, tissue, or organism, will also play a role in precision medicine for neurological disorders. In June 2021, the United States Food and Drug Adminstration approved the first therapy addressing the underlying biology of Alzheimer's disease. The drug, Biogen's Aducanumab, is a monoclonal antibody therapy that works by clearing a substance known as beta-amyloid, a protein that scientists believe causes Alzheimer's, from the brain. The drug, which was found to exhibit a unique proteomic profile upon treatment in mice, was the first approved for Alzheimer's in 20 years, and while it is thought to be effective in a limited number of Alzheimer's disease cases (namely, people in the early stages of Alzheimer's), it represents a step forward in neurodegenerative disease research.

The FDA's approval of Aduhelm, which was under an accelerated timeframe, has created more interest in the area of Alzheimer's and Parkinson's disease treatments. Scientists believe that a protein called tau is more closely associated with dementia than beta-amyloid, so they are also seeking to develop drugs targeting tau protein. In the realm of Parkinson's disease, research is underway to target a compound called alpha-synuclein, which, like amyloid beta and tau protein in Alzheimer's, is associated with cognitive decline in Parkinson's disease. There are a number of approaches in development to target tau. Investors can expect many more biotech companies and venture firms moving into this space to develop innovative and alternative treatments.

This work is not without significant challenges. One obstacle in neurodegenerative research is creating drugs that can bypass the brain's blood-brain-barrier, which keeps the brain safe from toxic substances or pathogens that would otherwise make their way into the brain. Another challenge is the fact that neurodegeneration affects a subset of neurons, which may have different levels of vulnerability to such disease. It is not yet fully clear which factors predispose certain neurons to develop pathology over others.

Yet as drug discovery continues to leverage the latest techniques in genomics, transcriptomics, and proteomics, and combinations of these technologies, this will unlock new potential for companies to create novel, increasingly personalized, therapies. For example, advances in genomics may provide insight into how neurodegeneration occurs in the brain.

Drug discovery in neurodegeneration also overlaps with that of other diseases, due to common disease pathways. For example, phosphatidylinositol 3-Kinase (PI3K) inhibitors are implicated not only in COVID-19 and breast cancer, but also Parkinson's Disease. Stem cell therapies, which could benefit patients suffering from many conditions, can also have significant applications in the neurodegenerative realm. Stem cells could potentially be used to restore lost brain tissue, or to release compounds such as anti-inflammatory factors and growth factors supporting repair of the nervous system. Stem cell therapies, which are already in use for conditions such as cancer, could thereby restore function to neurodegenerative patients. Therefore, advances made in the treatment of other disease states could potentially innovate the field of neurodegeneration as well.

PRLog ID: http://www.prlog.org/12894142

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Braeden Lichti - Investing in Precision Medicine to Yield New Treatments for Neurodegenerative Diseases - PRNewswire

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Mercks anti-PD-1 therapy, for the adjuvant treatment of patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. The approval is based on data from the pivotal Phase 3 KEYNOTE-564 trial, in which KEYTRUDA demonstrated a statistically significant improvement in disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared to placebo. Median DFS has not been reached for either group.

Despite decades of research, limited adjuvant treatment options have been available for earlier-stage renal cell carcinoma patients who are often at risk for recurrence. In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence, said Dr. Toni K. Choueiri, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School. With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see Selected Important Safety Information below.

KEYTRUDA is foundational for the treatment of patients with certain advanced cancers, and this approval marks the fourth indication for KEYTRUDA in earlier stages of cancer, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. KEYTRUDA is now the first immunotherapy approved for the adjuvant treatment of certain patients with renal cell carcinoma. This milestone is a testament to our commitment to help more people living with cancer.

In RCC, Merck has a broad clinical development program exploring KEYTRUDA, as monotherapy or in combination, as well as other investigational products across multiple settings and stages of RCC, including adjuvant and advanced or metastatic disease.

Data Supporting the Approval

KEYTRUDA demonstrated a statistically significant improvement in DFS in patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared with placebo (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010). The trial will continue to assess overall survival (OS) as a secondary outcome measure.

In KEYNOTE-564, the median duration of exposure to KEYTRUDA was 11.1 months (range, 1 day to 14.3 months). Serious adverse reactions occurred in 20% of these patients receiving KEYTRUDA. Serious adverse reactions (1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% of those treated with KEYTRUDA, including one case of pneumonia. Adverse reactions leading to discontinuation occurred in 21% of patients receiving KEYTRUDA; the most common (1%) were increased alanine aminotransferase (1.6%), colitis and adrenal insufficiency (1% each). The most common adverse reactions (all grades 20%) in the KEYTRUDA arm were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%) and hypothyroidism (21%).

About KEYNOTE-564

KEYNOTE-564 (ClinicalTrials.gov, NCT03142334) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating KEYTRUDA as adjuvant therapy for RCC in 994 patients with intermediate-high or high risk of recurrence of RCC or M1 no evidence of disease (NED). Patients must have undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion[s] in M1 NED participants) with negative surgical margins for at least four weeks prior to the time of screening. Patients were excluded from the trial if they had received prior systemic therapy for advanced RCC. Patients with active autoimmune disease or a medical condition that required immunosuppression were also ineligible. The major efficacy outcome measure was investigator-assessed DFS, defined as time to recurrence, metastasis or death. An additional outcome measure was OS. Patients were randomized (1:1) to receive KEYTRUDA 200 mg administered intravenously every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity.

About Renal Cell Carcinoma (RCC)

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In the U.S., it is estimated there will be more than 76,000 new cases of kidney cancer diagnosed and almost 14,000 deaths from the disease in 2021.

About Mercks Early-Stage Cancer Clinical Program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (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 1,600 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 patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications 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:

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.

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 HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

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. 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):

Non-muscle Invasive Bladder Cancer

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient 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) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

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.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

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 locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (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 cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

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 adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. 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 TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently 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. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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FDA Approves Merck's KEYTRUDA (pembrolizumab) as Adjuvant Therapy for Certain Patients With Renal Cell Carcinoma (RCC) Following Surgery - Business...