Incyte (INCY) Announces Positive Results on Jakafi for GVHD

Incyte Corp announced that the phase II trial, REACH1, evaluating lead drug Jakafi in combination with corticosteroids for the treatment of patients with steroid-refractory acute graft-versus-host disease (GVHD), met its primary endpoint.

The data from the study showed that Jakafi demonstrated an overall response rate (ORR) of 55% at day 28. Moreover, the number of patients achieving a response at any point of time, during the study, was 73%. Propelled by positive data from the REACH 1 study, Incyte now plans to file a Supplemental New Drug Application (sNDA) with the FDA for the label expansion of Jakafi, for the treatment of steroid-refractory acute GVHD, during the third quarter of 2018.

Incyte also plans to present full details from the study, at an upcoming scientific meeting.

We note that Jakafi, a first-in-class JAK1/JAK2 inhibitor, is already approved by the FDA for the treatment of people with polycythemia vera (PV), who have had an inadequate response to or are intolerant of hydroxyurea.

The drug is also indicated for the treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF and post–essential thrombocythemia MF. Incyte has a collaboration agreement with Novartis (NVSFree Report) for Jakafi. While Jakafi is marketed by Incyte in the United States, it is marketed by Novartis outside the country.

Jakafi’s performance has been impressive so far. In order to expand the patient population and increase the commercial potential of the drug, the company is working on expanding the drug’s label, further. In October 2017, the FDA approved a label update of the drug to include the addition of new patient-reported outcome (PRO) data from the COMFORT-I study as well as updating the warning related to progressive multifocal leukoencephalopathy.

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Small Number of Myelofibrosis Patients Develop Aggressive Lymphoma from JAK Inhibition

BY Brielle Urciuoli
PUBLISHED June 25, 2018

While JAK inhibitors have proven to be an effective treatment for patients with myelofibrosis, a type of myeloproliferative neoplasm (MPN), they may come with a severe downside – in particular, a 16-fold increase in the chance of developing a B-cell lymphoma, according to recent research published in the journal Blood.

“Many patients profit from this treatment and survive with good quality of life. Therefore, it is important to study potential long-term side effects of this therapy,” study author Ulrich Jager, M.D., head of the Division of Hematology and Haemostaseology at the Medical University of Vienna in Austria, said in an interview with CURE.

Researchers examined 626 patients with MPNs who were diagnosed and treated at the Medical University of Vienna between the years of 1997 and 2016. Of these patients, 69 with myelofibrosis were treated with a JAK1/2 inhibitor for lymphoma development, which included Jakafi (ruxolitinib), gandotinib, fedratinib or momelotinib.

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Structure of protein pair provides blueprint for future drugs

Walter and Eliza Hall Institute researchers have visualised for the first time how the protein SOCS1 ‘switches off’ cell signalling to dampen immune responses and block cancer growth.

The atomic-level structure of SOCS1 binding to its partner protein JAK could guide the development of drugs that alter disease-causing cell signalling pathways, and may have applications for treating some blood cancers, including leukaemias.

The research, led by Dr Nick Liau, Dr Nadia Kershaw, Associate Professor Jeff Babon and Professor Nick Nicola, was published in the journal Nature Communications.


– The SOCS1 protein binds to JAK proteins to ‘switch off’ cell signalling, which dampens processes including immune responses and cancer growth.

– Our researchers have used structural biology to visualise how SOCS1 binds to JAK proteins in never-before seen detail.

– The detailed structure may guide the development of new drugs that modify JAK activity, amplifying or dampening cell responses, with potential applications in cancer therapies.

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MPN Field ‘Hitting Its Stride,’ But More Work Is Needed

New biomarkers are being investigated in myeloproliferative neoplasms (MPNs), pointing toward a future of advances in the field, according to David S. Snyder, M.D., associate chair and professor of the Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope.

“The field of MPNs is hitting its stride with new molecular markers that are being defined,” Snyder said in an interview with OncLive, a sister publication of CURE.

Currently understood driver mutations include JAK2, CALR and NPL, but researchers are now looking at secondary mutations and their significance toward a patient’s prognosis. Snyder said that these findings will lead to targeted therapies, as they did for Jakafi (ruxolitinib), a JAK2 inhibitor that was the only FDA-approved drug that was developed for myelofibrosis.

Jakafi may also work for patients with a CALR mutation as a different mechanism, according to Snyder. He explained that there are two types of CALR mutations: type 1, which is a deletion in the protein; and type 2, which is an insertion into the protein. The CALR mutations ultimately feed through the JAK2-STAT pathway, similar to the JAK2 pathway.

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Effect of MPN Diagnosis on Work, Employment Status

Many patients experience a negative impact on work productivity and employment status after a diagnosis of myeloproliferative neoplasm (MPN), according to a study published in BMC Cancer.

The clinical adverse effects of MPNs (eg, polycythemia vera [PV], essential thrombocytopenia [ET], myelofibrosis [MF]) are well known; risks for cardiovascular and thrombotic events and various other symptoms are increased. The impact of illness on the workplace and careers, however, have yet to be explored.

For this study, researchers sent the cross-sectional online survey “Living with MPNs” to patients with a myeloproliferative neoplasm. The survey consisted of approximately 100 questions related to MPN, focusing on factors such as diagnosis, symptoms, and changes in employment, work productivity, and daily activities. The Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP) was used to evaluate the effects of MPN on work productivity and activity for currently employed respondents, and the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) was used to measure symptom burden.

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Potential Combos With Ruxolitinib in Myelofibrosis

To date, the JAK inhibitor ruxolitinib (Jakafi) is the only FDA-approved therapy for the treatment of patients with myelofibrosis (MF); however, novel agents and combination regimens are in development to address some of the unmet needs in MF, including treating cases of anemia associated with MF and treatment with ruxolitinib, as well as increasing responses to the targeted therapy.

In an interview with Targeted Therapies in Oncology™ (TTO), at the meeting, Prithviraj Bose, MD, assistant professor, The University of Texas MD Anderson Cancer Center, discussed the findings of 2 combination trials with ruxolitinib to optimize outcomes for patients with MF.

TTO: What are the unmet needs that still exist in MF that you would like to see be resolved?

BOSE: Ruxolitinib is a very well-established choice for JAK1/2 inhibition, but we also have some limitations. It is great at shrinking the spleen and improving symptoms, and it extends overall survival [OS], but certain things don’t get that much better. For example, ruxolitinib causes anemia, which can make it hard for patients to stay on or go up to the optimal dose.

The unmet needs are (1) to have a drug that could circumvent the anemia with ruxolitinib, and maybe even the thrombocytopenia, so that patients can stay on ruxolitinib at an optimal dose for an extended period of time, and (2) the fact that ruxolitinib is not a cure. Even though it extends OS, MF is still not curable without allogeneic transplant. We need disease-modifying drugs, which, in combination with ruxolitinib, for example, will hopefully give us more biology-altering benefits.

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Pacritinib Can Fill Unmet Need in Myelofibrosis

The investigational agent pacritinib (CTI BioPharma) holds promise as a treatment option for patients with myelofibrosis and baseline thrombocytopenia, and previous concerns that led to a hold on clinical trials have now been dispelled.

In a pivotal trial, PERSIST-2, pacritinib was significantly more effective than the best available therapy, including ruxolitinib (Jakafi, Incyte), in reducing splenomegaly and trended toward a reduction in total symptom score in patients with myelofibrosis and thrombocytopenia.

The study was published online March 8 in JAMA Oncology. Ruxolitinib, which was approved in 2011 and the first drug ever approved for myelofibrosis, is not safe for patients with low platelet counts.

“The label on ruxolitinib states it is for patients with platelet counts above 50,000, so it isn’t a viable option for those with thrombocytopenia,” said lead author, John Mascarenhas, MD, associate professor of medicine, hematology and medical oncology, at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York.

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Recruiting: New Phase 2 Clinical Trial for MF Patients on Ruxolitinib

People with myelofibrosis who are currently receiving ruxolitinib therapy may be eligible for a new phase II clinical trial led by Dr. Ellen Ritchie.

Navitoclax is an investigational agent that inhibits a family of BCL proteins. These proteins block some of the enzymes that keep cancer cells from dying and by inhibiting these proteins, navitoclax may cause the cancer cells to die.  Ruxolitinib is approved by the FDA for the treatment of myelofibrosis. Ruxolitinib blocks a protein called Janus-associated kinases (JAK) which may help keep abnormal blood cells or cancer cells from growing.

The purpose of this study is to evaluate the addition of navitoclax to ruxolitinib in patients who have been receiving ruxolitinib alone. Ruxolitinib treatment alone has not been fully controlling disease which is evident by an enlarged spleen. Preclinical data suggest that the combination of navitoclax with ruxolitinib are synergistic and that navitoclax may help to overcome disease resistance to ruxolitinib.

The study will help to determine the effect of the combination of navitoclax plus ruxolitinib on your cancer. The study will evaluate how the efficacy and safety of the drug.

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Study Finds Nutritional Changes Can Improve Symptom Burden

Patients with MPNs have increased inflammatory cytokines, which contribute to symptoms such as fatigue, night sweats and bone pain, as well as low cholesterol and weight loss related to nutritional deficiencies.
BY Katie Kosko
PUBLISHED March 05, 2018
DIET AND SUPPLEMENT USE can help alleviate some of the symptom burden experienced by patients with myeloproliferative neoplasms (MPNs), according to a study conducted by Mayo Clinic researchers.

Patients with MPNs have increased inflammatory cytokines, which contribute to symptoms such as fatigue, night sweats and bone pain, as well as low cholesterol and weight loss related to nutritional deficiencies.

To examine the habits, needs and preferences among this population, researchers used an internet-based survey through the Mayo Clinic Survey Research Center and promoted it on many MPN-focused websites and communities in February 2017. The survey included data on demographics, disease characteristics, nutritional habits, supplement use and symptom burden using the Myeloproliferative Neoplasm Symptom Assessment Form and Total Symptom Score.

The 1,329 patients who responded to the survey represented 37 countries and had the following types of disease: myelofibrosis, 24 percent; polycythemia vera, 37 percent; and essential thrombocythemia, 38 percent. Of those patients, 1,131 consented to taking the survey. The average total symptom score was 31.

Survey results showed that 34 percent of patients endorsed using diet to help control their symptoms or disease, 23 percent had food allergies or intolerances and 31 percent followed a specific or restricted diet.

Nearly all patients who responded (96 percent) said they would be willing to eat only certain foods if it helped to control symptom burden, stabilize their disease or reduce the risk of it worsening (98 percent). Over-the-counter supplements were used by 72 percent of patients, more often by women (74 percent) than men (66 percent).

Supplement users also were more likely to be older, have lower self-reported body mass index and engage in at least 30 minutes of physical activity.

Lower symptom score was associated with alcohol intake, baked foods, dairy and pasta; higher score, with fast food, premade snacks, soda and refined sugar. Symptom burden was significantly lower among patients using amino acid supplements and N-acetylcysteine, but significantly higher in those taking Bach flower remedies

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Qiagen JAK2 Test Gets FDA Clearance for Additional Blood Cancer Types

NEW YORK (GenomeWeb) – Qiagen said after the close of the market on Tuesday that it received US Food and Drug Administration clearance for its Ipsogen JAK2 RGQ PCR Kit for additional use in the diagnosis of all myeloproliferative neoplasms (MPNs).

In March 2017 the FDA cleared the assay as a qualitative in vitro diagnostics test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood to aid in the diagnosis of the blood cancer polycythemia vera.

The new FDA clearance now covers two additional types of MPNs: essential thrombocythemia and primary myelofibrosis.

The assay runs on Qiagen’s Rotor-Gene Q MDx instrument, a component of the modular QiaSymphony family of laboratory automation products.

Qiagen said that it is the exclusive worldwide licensee of intellectual property covering the detection of the JAK2 V617F mutation for diagnostic purposes, and that it recently reached a settlement with an unspecified molecular diagnostics industry supplier in Europe, which agreed to stop selling its own JAK2 V617F test kit.

“We are eager to expand the use of our Ipsogen JAK2 assay, which is already available in Europe and other markets, for use in a wider range of patients in the US,” Thierry Bernard, senior vice president and head of Qiagen’s molecular diagnostics business area, said in a statement. The assay “makes it easier for hematologists and oncologists to follow recommended diagnostic testing algorithms and international guidelines for their patients suspected of having MPNs.”

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