CRISPR combines with stem cell therapy to reverse diabetes in mice – New Atlas

For a few years now, scientists at Washington University have been working on techniques to turn stem cells into pancreatic beta cells as a way of addressing insulin shortages in diabetics. After some promising recent strides, the team is now reporting another exciting breakthrough, combining this technique with the CRISPR gene-editing tool to reverse the disease in mice.

The pancreas contains what are known as beta cells, which secrete insulin as a way of tempering spikes in blood-sugar levels. But in those with diabetes, these beta cells either die off or dont function as they should, which means sufferers have to rely on diet and or regular insulin injections to manage their blood-sugar levels instead.

One of the ways scientists are working to replenish these stocks of pancreatic beta cells is by making them out of human stem cells, which are versatile, blank slate-like cells that can mature into almost any type of cell in the human body. The Washington University team has operated at the vanguard of this technology with a number of key breakthroughs, most recently with a cell implantation technique that functionally cured mice with diabetes.

The researchers are continuing to press ahead in search of new and improved methods, and this led them to the CRISPR gene-editing system, which itself has shown real promise as a tool to treat diabetes. The hope was that CRISPR could be used to correct genetic defects leading to diabetes, combining with the stem cell therapy to produce even more effective results.

As a proof of concept, the scientists took skin cells from a patient with a rare genetic type of diabetes called Wolfram syndrome, which develops during childhood and typically involves multiple insulin injections each day. These skin cells were converted into induced pluripotent stem cells, which were in turn converted into insulin-secreting beta cells. But as an additional step, CRISPR was used to correct a genetic mutation that causes Wolfram syndrome.

These edited beta cells were then pitted against non-edited beta cells from the same batch in test tube experiments and in mice with a severe type of diabetes. The edited cells proved more efficient at secreting insulin and when implanted under the skin in mice, reportedly caused the diabetes to quickly disappear. The rodents that received the unedited beta cells remained diabetic.

This is the first time CRISPR has been used to fix a patients diabetes-causing genetic defect and successfully reverse diabetes, said co-senior investigator Jeffrey R. Millman. For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene. But we see this as a stepping stone toward applying gene therapy to a broader population of patients with diabetes.

The researchers are now continuing to work on improving the beta cell production technique, which in the future could involve cells taken form the blood or even urine, rather than the skin. They believe that further down the track this therapy could prove useful in treating both type 1 and type 2 diabetes, by correcting mutations that arise from genetic and environmental factors, and possibly be used to treat other conditions, as well.

We basically were able to use these cells to cure the problem, making normal beta cells by correcting this mutation, said co-senior investigator Fumihiko Urano. Its a proof of concept demonstrating that correcting gene defects that cause or contribute to diabetes in this case, in the Wolfram syndrome gene we can make beta cells that more effectively control blood sugar. Its also possible that by correcting the genetic defects in these cells, we may correct other problems Wolfram syndrome patients experience, such as visual impairment and neurodegeneration.

The research was published in the journal Science Translational Medicine.

Source: Washington University

View post:
CRISPR combines with stem cell therapy to reverse diabetes in mice - New Atlas

Graft Versus Host Disease: Opportunity Analysis and Forecasts to 2028 – ResearchAndMarkets.com – Yahoo Finance

The "Graft Versus Host Disease: Opportunity Analysis and Forecasts to 2028" report has been added to ResearchAndMarkets.com's offering.

The GvHD market is expected to undergo significant change and growth over the next 10 years across the seven major pharmaceutical markets (7MM; US, France, Germany, Italy, Spain, UK, and Japan) covered in this report.

This report analyzes the current GvHD treatment and prophylaxis landscape and provides detailed insights into the market dynamics of this newly recognized disorder. This analysis also includes the evaluation of the commercial and clinical profiles of drugs in development for GvHD, and their sales projections within GvHD over the 2018-2028 forecast period.

Key Highlights

Report Scope

The report will enable you to:

Key Topics Covered

1 Table of Contents

1.1 List of Tables

1.2 List of Figures

2 Executive Summary

2.1 Strong Growth Expected in the GvHD Marketplace from 2018-2028

2.2 Lack of Consensus on Clinical Trial Endpoints

2.3 GvHD Unmet Needs Expected to Be Partially Addressed

2.4 Opportunity Remains for GvHD Prophylaxis Candidates

2.5 Jakafi Approval for Both Acute and Chronic GvHD Will Drive Sales

2.6 What Do Physicians Think?

3 Introduction

3.1 Catalyst

3.2 Related Reports

3.3 Upcoming Related Reports

4 Disease Overview

4.1 Etiology and Pathophysiology

4.1.1 Etiology

4.1.2 Pathophysiology

4.2 Classification and Prognosis

4.2.1 Acute GvHD

4.2.2 Chronic GvHD

5 Epidemiology

6 Current Treatment Options

7 Unmet Needs and Opportunity Assessment

8 R&D Strategies

9 Pipeline Assessment

10 Pipeline Valuation Analysis

Companies Mentioned (A-Z)

For more information about this report visit https://www.researchandmarkets.com/r/50i38p

View source version on businesswire.com: https://www.businesswire.com/news/home/20200423005325/en/

Contacts

ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

Go here to read the rest:
Graft Versus Host Disease: Opportunity Analysis and Forecasts to 2028 - ResearchAndMarkets.com - Yahoo Finance

Novartis’ Jakavi bests current therapy for GvHD – PharmaTimes

Results of the Phase III REACH2 study show that Novartis' Jakavi (ruxolitinib) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GvHD) compared to best available therapy (BAT).

In the study, patients treated with Jakavi experienced significantly greater overall response rate (ORR) compared to BAT (62% vs. 39%) at Day 28, the primary endpoint of the study.

For the key secondary endpoint, those in the Jakavi group maintained significantly higher durable ORR (40% vs. 22% at eight weeks, and Novartis' drug was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months as well as showing a positive trend with other secondary endpoints, including duration of response.

The findings are particularly pertinent as GvHD, a serious and common complication of allogeneic stem cell transplants, has a one-year death rate as high as 80% in its acute form, and REACH2 is the first Phase III study in acute GvHD to have met its primary endpoint.

"Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy," said Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany.

"These new data from REACH2 showing superiority of Jakavi over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition."

Also of note, the first said no new safety signals were observed in REACH2, and adverse events (AEs) attributable to treatment were consistent with the known safety profile of Jakavi, the most common of which were thrombocytopaenia, anaemia and cytomegalovirus infection.

"Compelling results from REACH2, the first successful randomized Phase III trial in patients with steroid-refractory acute graft-versus-host-disease, give us confidence in the potential of Jakavi to confront this difficult condition," said John Tsai, head Global Drug Development and chief medical officer at Novartis. "We look forward to initiating discussions with ex-US regulatory authorities."

The results are published in The New England Journal of Medicine.

Read the rest here:
Novartis' Jakavi bests current therapy for GvHD - PharmaTimes

FDA Approves New Therapy for Triple Negative Breast Cancer That Has Spread, Not Responded to Other Treatments – Herald-Mail Media

SILVER SPRING, Md., April 22, 2020 /PRNewswire/ --Today, the U.S. Food and Drug Administration granted accelerated approval to Trodelvy (sacituzumab govitecan-hziy) for the treatment of adult patients with triple-negative breast cancer that has spread to other parts of the body. Patients must have received at least two prior therapies before taking Trodelvy.

"Metastatic triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Chemotherapy has been the mainstay of treatment for triple-negative breast cancer. The approval of Trodelvy today represents a new targeted therapy for patients living with this aggressive malignancy," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. "There is intense interest in finding new medications to help treat metastatic triple-negative breast cancer. Today's approval provides patients who've already tried two prior therapies with a new option."

Trodelvy is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate, meaning that the drug targets the Trop-2 receptor that helps the cancer grow, divide and spread, and is linked to topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells. Approximately two of every 10 breast cancer diagnoses worldwide are triple-negative. Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2(HER2) protein. Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.

"As part of FDA's ongoing and aggressive commitment to address the novel coronavirus pandemic, we continue to keep a strong focus on patients with cancer who constitute a vulnerable population at risk of contracting the disease," said Pazdur. "At this critical time, we continue to expedite oncology product development. This application was approved more than a month ahead of the FDA goal date an example of that commitment. Our staff is continuing to meet with drug developers, academic investigators, and patient advocates to push forward the coordinated review of treatments for cancer."

The FDA approved Trodelvy based on the results of a clinical trial of 108 patients with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease. The efficacy of Trodelvy was based on the overall response rate (ORR) which reflects the percentage of patients that had a certain amount of tumor shrinkage. The ORR was 33.3%, with a median duration of response of 7.7 months. Of the patients with a response to Trodelvy, 55.6% maintained their response for 6 or more months and 16.7% maintained their response for 12 or more months.

The prescribing information for Trodelvy includes a Boxed Warning to advise health care professionals and patients about the risk of severe neutropenia (abnormally low levels of white blood cells) and severe diarrhea. Health care professionals should monitor patient's blood cell counts periodically during treatment with Trodelvy and consider treatment with a type of therapy called granulocyte-colony stimulating factor (G-CSF), which stimulates the bone marrow to produce white blood cells called granulocytes and stem cells and releases them into the bloodstream, to help prevent infection, and should initiate anti-infective treatment in patients with febrile neutropenia (development of fever when white blood cell are abnormally low).

Additionally, health care professionals should monitor patients with diarrhea and give fluid, electrolytes, and supportive care medications, as needed. Trodelvy may need to be withheld, dose reduced or permanently discontinued for neutropenia or diarrhea. Trodelvy can cause hypersensitivy reactions including severe anaphylactic (allergic) reactions. Patients should be monitored for infusion-related reactions and health care professionals should discontinue Trodelvy if severe or life-threatening reactions occur. If patients experience nausea or vomiting while taking Trodelvy, health care professionals should use antiemetic preventive treatment, to prevent nausea and vomitting. Patients with reduced uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) activity are at increased risk for neutropenia following initiation of Trodelvy treatment.

The most common side effects for patients taking Trodelvy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia (hair loss), constipation, decreased appetite, rash and abdominal pain.

Women who are pregnant should not take Trodelvy because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to inform females of reproductive age to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Male patients with female partners of reproductive potential should also use effective contraception during treatment with Trodelvy and for three months after the last dose.

Trodelvy was granted accelerated approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Trodelvy's clinical benefit.

The FDA granted this application Priority Review andBreakthrough Therapydesignation, which expedites the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Trodelvy was also granted Fast Trackdesignation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need.

The FDA granted approval of Trodelvy to Immunomedics, Inc.

Additional Resources:

Media Contact:Nathan Arnold, 301-796-6248Consumer Inquiries: Emailor 888-INFO-FDA

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Continue reading here:
FDA Approves New Therapy for Triple Negative Breast Cancer That Has Spread, Not Responded to Other Treatments - Herald-Mail Media

Incyte Announces Pivotal REACH2 Study Data Published in NEJM Highlight Superior Efficacy of Ruxolitinib (Jakafi) versus Best Available Therapy in…

- Phase 3 REACH2 data demonstrate that ruxolitinib (Jakafi) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GVHD) compared to best available therapy (BAT)

- Results show a significantly greater overall response rate (ORR) in patients treated with ruxolitinib (62%) compared to BAT (39%) 1,2

- GVHD is a serious and common complication of allogeneic stem cell transplants with a one-year mortality rate as high as 80% in patients who develop acute GVHD3-5

- The results, published in The New England Journal of Medicine, were also selected for an oral presentation during the Presidential Symposium at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting to be held 30 August to 2 September in Madrid, Spain

Incyte (Nasdaq:INCY) today announced that data from the Phase 3 REACH2 study have been published in The New England Journal of Medicine demonstrating that ruxolitinib (Jakafi) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GVHD) compared to best available therapy (BAT). The results of REACH2, the first Phase 3 study of ruxolitinib in acute GVHD to have met its primary endpoint, reinforce findings from the previously-reported Phase 2 REACH1 study.

In REACH2, patients treated with ruxolitinib experienced a significantly greater overall response rate (ORR) vs. BAT (62% vs. 39%; p<0.001) at Day 28, the primary endpoint of the study. For the key secondary endpoints, patients treated with ruxolitinib maintained significantly higher durable ORR (40% vs. 22%; p<0.001) at Day 56. In addition, ruxolitinib was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months; hazard ratio 0.46, 95% CI, 0.35 to 0.60) and showed a positive trend with other secondary endpoints, including duration of response1,2.

No new safety signals were observed, and the ruxolitinib safety profile in REACH2 was consistent with that seen in previously reported studies in steroid-refractory acute GVHD. The most frequently reported adverse events among study participants were thrombocytopenia and anemia. While 38% and 9% of patients required ruxolitinib and BAT dose modifications, the number of patients who discontinued treatment due to AEs was low (11% and 5%, respectively)1,2.

"The results from the REACH2 study reinforce findings from the pivotal REACH1 trial and demonstrate the potential that ruxolitinib has to effectively and safely improve outcomes for patients with GVHD," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "We are committed to continuing our research in GVHD with the goal of providing more effective treatment options for patients living with this disease, and look forward to the results of the REACH3 study in steroid-refractory chronic GVHD later this year."

The REACH2 data were also accepted as an oral presentation as part of the Presidential Symposium at the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting to be held 30 August to 2 September in Madrid, Spain.

"Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy," said Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. "These new data from REACH2 showing superiority of ruxolitinib over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition."

In 2019, Jakafi (ruxolitinib) was approved by the U.S. Food and Drug Administration for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older, based on the positive results of the Phase 2 REACH1 trial6. The Phase 3 REACH3 study in patients with steroid-refractory chronic GVHD is ongoing and results are expected in the second half of this year. Jakafi is marketed by Incyte in the U.S.; ruxolitinib (Jakavi) is licensed to Novartis ex-U.S.

The NEJM publication of the REACH2 results is available online.

Story continues

About REACH2

REACH2 (NCT02913261), a randomized, open-label, multicenter Phase 3 study sponsored by Novartis and conducted in collaboration with and co-funded by Incyte , is evaluating the safety and efficacy of ruxolitinib compared with best available therapy in patients with steroid-refractory acute GVHD.

The primary endpoint was overall response rate (ORR) at Day 28, defined as the proportion of patients demonstrating a best overall response (complete response or partial response). Secondary endpoints include durable ORR at Day 56, ORR at Day 14, duration of response, overall survival and event-free survival, among others. For more information about the study, please visit https://clinicaltrials.gov/ct2/show/NCT02913261.

About REACH

The REACH clinical trial program evaluating ruxolitinib in patients with steroid-refractory GVHD, includes the randomized pivotal Phase 3 REACH2 and REACH3 trials, conducted in collaboration with Novartis. The ongoing REACH3 trial is evaluating patients with steroid-refractory chronic GVHD with results expected later this year. For more information about the REACH3 study, please visit https://clinicaltrials.gov/ct2/show/NCT03112603.

The REACH program was initiated with the Incyte-sponsored REACH1 trial, a prospective, open-label, single-cohort, multicenter, pivotal Phase 2 trial (NCT02953678) evaluating Jakafi in combination with corticosteroids in patients with steroid-refractory grade II-IV acute GVHD. For more information about the study, including trial results, please visit https://clinicaltrials.gov/show/NCT02953678.

About Jakafi (ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. FDA for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea, in adults with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF and for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: for certain types of MF and PV - low platelet or low red blood cell counts, bruising, dizziness, headache, and diarrhea; and for acute GVHD low platelet, red or white blood cell counts, infections, and fluid retention.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have a high level of fat in your blood (high blood cholesterol or triglycerides), had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breast-feed during treatment with Jakafi and for 2 weeks after the final dose.

Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at http://www.jakafi.com.

About Incyte

Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements about the REACH2 data, when results from the REACH3 study will be available, the effect of the REACH2 results on patients with GVHD, and the overall REACH program, contain predictions, estimates and other forward-looking statements.

These forward-looking statements are based on the Companys current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA; the Companys dependence on its relationships with its collaboration partners; the efficacy or safety of the Companys products and the products of the Companys collaboration partners; the acceptance of the Companys products and the products of the Companys collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; and other risks detailed from time to time in the Companys reports filed with the Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2019. The Company disclaims any intent or obligation to update these forward-looking statements.

References

View source version on businesswire.com: https://www.businesswire.com/news/home/20200422005739/en/

Contacts

Incyte Contacts Media Jenifer Antonacci+1 302 498 7036jantonacci@incyte.com

Catalina Loveman+1 302 498 6171cloveman@incyte.com

Investors Michael Booth, DPhil+1 302 498 5914mbooth@incyte.com

View original post here:
Incyte Announces Pivotal REACH2 Study Data Published in NEJM Highlight Superior Efficacy of Ruxolitinib (Jakafi) versus Best Available Therapy in...