On October 13, 2017 Impact Biomedicines ("Impact") reported its launch to pioneer the development of life-changing treatments for patients with myeloproliferative neoplasms and other cancers (Press release, Impact Biomedicines, OCT 13, 2017, View Source [SID1234520974]). The Company’s pipeline is centered around fedratinib, a potent and highly selective oral small molecule JAK2 kinase inhibitor that is being developed initially for the treatment of myelofibrosis (MF) and polycythemia vera (PV). In conjunction with this launch, Impact is pleased to share that the U.S. Food and Drug Administration (FDA) has removed the clinical hold placed on fedratinib and that the company has received $22.5 million from Medicxi through a Series A financing.

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Impact was formed in 2016 after acquisition of Sanofi’s full rights for the global development and commercialization of fedratinib. The majority equity holders in Impact include the co-founders and Medicxi, with Sanofi retaining a minority stake.

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

The clinical package for fedratinib includes data from a total of 18 studies completed in 877 subjects. In JAKARTA-1, a completed international Phase 3 pivotal trial for the treatment of myelofibrosis, fedratinib met its primary and secondary endpoints by reducing spleen size in 47% of patients by ≥35% at 24 weeks (p<0.0001) and improving symptom score in 36% of patients by ≥50% at 24 weeks (p< 0.0001). Comparable responses were seen in patients with normal or low platelet counts and thrombocytopenia was similar between placebo and the target dose of 400mg. In JAKARTA-2, a follow-on study in patients who were unresponsive to all other available therapies, including patients who were either Jakafi (ruxolitinib) resistant or intolerant, fedratinib showed similar activity. In that study, 55% of patients who had failed or were intolerant to ruxolitinib experienced a spleen size reduction of ≥35% with fedratinib. Notably, responses were noted in 63% of patients intolerant to ruxolitinib and 61% of patients who had lost ruxolitinib response. Currently, ruxolitinib is the only drug approved by the FDA to treat patients with MF and PV. The most common adverse events for fedratinib were hematological (anemia) and gastrointestinal (nausea, diarrhea and vomiting). The results of these trials have been published in leading peer-reviewed journals.

"The decision to discontinue the development of fedratinib in 2013 was heartbreaking for the patients who were experiencing positive responses while in clinical trials. There are very limited therapeutic options for these patients and fedratinib was active in most patients when nothing else had worked. Because of the very high unmet medical need in MF, the Impact team completed a thorough review of the available data, including careful due diligence into the potential cases of WE and I am glad to report that as a result of this effort, the FDA has lifted the clinical hold," said John Hood, Ph.D., Chief Executive Officer of Impact. "In addition to MF, Impact intends to pursue multiple clinical indications for fedratinib to realize its potential as a best-in-class JAK2 kinase inhibitor."

To support the Company’s drug development and manufacturing efforts and the build out of the management team, Impact closed a $22 million Series A financing with Medicxi.

"We’ve made it a point to double down and invest more in maturing life science companies who are delivering innovation where it’s needed most. In line with our ‘asset-centric’ approach, we believe Impact is doing just that by reviving fedratinib with a thoughtful development approach and due diligence," said Kevin Johnson, Impact board member and Co-Founder of Medixci. "We are confident that the dedicated team at Impact has the vision and skill to create a sustainable long-term business around fedratinib."

The development of fedratinib is being led by a highly skilled and devoted team, including members of the original TargeGen team, where fedratinib was first developed prior to its acquisition by Sanofi.

Dr. Hood serves as Chief Executive Officer of Impact Biomedicines. Prior to founding Impact, he was co-founder and Chief Scientific Officer of Samumed, a pharmaceutical platform company focused on advancing regenerative medicine and oncology applications. Prior to that, Dr. Hood was Director of Research and co-inventor of fedratinib at TargeGen, Inc., (subsequently acquired by Sanofi SA), where he led a team identifying small molecule kinase inhibitors for the treatment of eye diseases and cancer. He is an inventor on 100+ patents and author on 50+ scientific articles. Dr. Hood obtained a Ph.D. in medical physiology and B.S. in biochemistry from Texas A&M University.

Dr. Catriona Jamieson serves as Interim Chief Medical Officer of Impact Biomedicines, and co-founder. Concurrently, Dr. Jamieson is a Professor of Medicine and Chief of Regenerative Medicine, Deputy Director of the Sanford Stem Cell Clinical Center, Co-leader of the Hematologic Malignancies Program, and Director of Stem Cell Research at the Moores UC San Diego Cancer Center. She specializes in myeloproliferative neoplasms and leukemia, and was the principal investigator on several fedratinib trials. Dr. Jamieson obtained an M.D., a Ph.D. in microbiology and a B.S. in Genetics from the University of British Columbia prior to completing fellowships in hematology and bone marrow transplantation at Stanford University and being recruited to UC San Diego.

About Myeloproliferative Neoplasms
Myeloproliferative Neoplasms (MPN) are a closely-related group of blood cancers in which the body, specifically the bone marrow, makes too many red blood cells, platelets, or certain white blood cells. There are three types of blood cancers that comprise MPNs: Myelofibrosis, Polycythemia Vera and Essential Thrombocythemia. MPNs are characterized by the mutations of JAK2, MPL o

On October 13, 2017 Impact Biomedicines ("Impact") reported its launch to pioneer the development of life-changing treatments for patients with myeloproliferative neoplasms and other cancers (Press release, Impact Biomedicines, OCT 13, 2017, View Source [SID1234522384]). The Company’s pipeline is centered around fedratinib, a potent and highly selective oral small molecule JAK2 kinase inhibitor that is being developed initially for the treatment of myelofibrosis (MF) and polycythemia vera (PV). In conjunction with this launch, Impact is pleased to share that the U.S. Food and Drug Administration (FDA) has removed the clinical hold placed on fedratinib and that the company has received $22.5 million from Medicxi through a Series A financing.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Impact was formed in 2016 after acquisition of Sanofi’s full rights for the global development and commercialization of fedratinib. The majority equity holders in Impact include the co-founders and Medicxi, with Sanofi retaining a minority stake.

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

The clinical package for fedratinib includes data from a total of 18 studies completed in 877 subjects. In JAKARTA-1, a completed international Phase 3 pivotal trial for the treatment of myelofibrosis, fedratinib met its primary and secondary endpoints by reducing spleen size in 47% of patients by >35% at 24 weeks (p<0.0001) and improving symptom score in 36% of patients by >50% at 24 weeks (p< 0.0001). Comparable responses were seen in patients with normal or low platelet counts and thrombocytopenia was similar between placebo and the target dose of 400mg. In JAKARTA-2, a follow-on study in patients who were unresponsive to all other available therapies, including patients who were either Jakafi (ruxolitinib) resistant or intolerant, fedratinib showed similar activity. In that study, 55% of patients who had failed or were intolerant to ruxolitinib experienced a spleen size reduction of >35% with fedratinib. Notably, responses were noted in 63% of patients intolerant to ruxolitinib and 61% of patients who had lost ruxolitinib response. Currently, ruxolitinib is the only drug approved by the FDA to treat patients with MF and PV. The most common adverse events for fedratinib were hematological (anemia) and gastrointestinal (nausea, diarrhea and vomiting). The results of these trials have been published in leading peerreviewed journals.

"The decision to discontinue the development of fedratinib in 2013 was heartbreaking for the patients who were experiencing positive responses while in clinical trials. There are very limited therapeutic options for these patients and fedratinib was active in most patients when nothing else had worked. Because of the very high unmet medical need in MF, the Impact team completed a thorough review of the available data, including careful due diligence into the potential cases of WE and I am glad to report that as a result of this effort, the FDA has lifted the clinical hold," said John Hood, Ph.D., Chief Executive Officer of Impact. "In addition to MF, Impact intends to pursue multiple clinical indications for fedratinib to realize its potential as a best-in-class JAK2 kinase inhibitor."

To support the Company’s drug development and manufacturing efforts and the build out of the management team, Impact closed a $22 million Series A financing with Medicxi.

"We’ve made it a point to double down and invest more in maturing life science companies who are delivering innovation where it’s needed most. In line with our ‘asset-centric’ approach, we believe Impact is doing just that by reviving fedratinib with a thoughtful development approach and due diligence," said Kevin Johnson, Impact board member and Co-Founder of Medixci. "We are confident that the dedicated team at Impact has the vision and skill to create a sustainable long-term business around fedratinib."

The development of fedratinib is being led by a highly skilled and devoted team, including members of the original TargeGen team, where fedratinib was first developed prior to its acquisition by Sanofi.

Dr. Hood serves as Chief Executive Officer of Impact Biomedicines. Prior to founding Impact, he was co-founder and Chief Scientific Officer of Samumed, a pharmaceutical platform company focused on advancing regenerative medicine and oncology applications. Prior to that, Dr. Hood was Director of Research and co-inventor of fedratinib at TargeGen, Inc., (subsequently acquired by Sanofi SA), where he led a team identifying small molecule kinase inhibitors for the treatment of eye diseases and cancer. He is an inventor on 100+ patents and author on 50+ scientific articles. Dr. Hood obtained a Ph.D. in medical physiology and B.S. in biochemistry from Texas A&M University.

Dr. Catriona Jamieson serves as Interim Chief Medical Officer of Impact Biomedicines, and co-founder. Concurrently, Dr. Jamieson is a Professor of Medicine and Chief of Regenerative Medicine, Deputy Director of the Sanford Stem Cell Clinical Center, Co-leader of the Hematologic Malignancies Program, and Director of Stem Cell Research at the Moores UC San Diego Cancer Center. She specializes in myeloproliferative neoplasms and leukemia, and was the principal investigator on several fedratinib trials. Dr. Jamieson obtained an M.D., a Ph.D. in microbiology and a B.S. in Genetics from the University of British Columbia prior to completing fellowships in hematology and bone marrow transplantation at Stanford University and being recruited to UC San Diego.

On October 16, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that final results of the dose-escalation part of the ongoing Phase I study investigating IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL), an orphan disease, were presented by Pr Martine Bagot, Principal Investigator and Head of the Dermatology Department at the Saint-Louis Hospital, Paris, in an oral presentation at the EORTC CLTF* Meeting in London on October 15, 2017 (Press release, Innate Pharma, OCT 13, 2017, View Source [SID1234520943]).

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These data confirm the good safety profile and promising activity of IPH4102 in this elderly and heavily pretreated patients population (n=25). The objective response rate in the 20 patients with Sézary syndrome was 50%; the ORR4** was 40%, the disease control rate (DCR), 90%, the median duration of response (DOR), 9.9 months and the median progression free survival (PFS), 10.8 months, respectively. Data on pruritus were reported for the first time and show substantial improvement in patients having a global clinical response but also in patients with stable disease. The Recommended Phase 2 Dose (RP2D) has been identified at 750 mg, a fixed dose equivalent to 10 mg/kg.

Expansion cohorts started, including 2 cohorts of 15 patients each in two CTCL subtypes: Sézary syndrome and transformed mycosis fungoides.

Biomarker results were presented in an oral presentation by Dr Maxime Battistella, Assistant Professor Pathology and Dermatopathology at St Louis Hospital and Université L. Diderot. The presentations are available in the IPH4102 section on Innate Pharma’s website.

On October 13, 2017 Janssen-Cilag International NV ("Janssen") reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended broadening the existing marketing authorisation for ZYTIGA (abiraterone acetate) plus prednisone / prednisolone to include an earlier stage of prostate cancer than its current indications (Press release, Johnson & Johnson, OCT 13, 2017, View Source [SID1234520915]). If approved by the European Commission, abiraterone acetate plus prednisone / prednisolone in combination with androgen deprivation therapy (ADT) can be used for the treatment of adult men with newly diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC).

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"As shown by the results from the LATITUDE study, adding abiraterone acetate plus prednisone / prednisolone to ADT alone significantly improves overall survival and radiographic progression-free survival in men with metastatic hormone-sensitive prostate cancer and high-risk features in comparison to treating patients with ADT alone, where median survival is currently less than three years. Today’s decision means we are one step forward in ensuring mHSPC men across Europe may be able to benefit from this treatment soon," said Professor Karim Fizazi, principal investigator of the LATITUDE trial and Head of the Medical Oncology Department at Institute Gustave Roussy.

The CHMP recommendation is based on data from the multinational, multicentre, randomised, double-blind, placebo-controlled Phase 3 study, LATITUDE. The trial was designed to determine if newly diagnosed patients with mHNPC who have high-risk prognostic factors benefit from the addition of abiraterone acetate and prednisone to androgen deprivation therapy (ADT) vs placebos and ADT.2 Data were presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) congress in Chicago, USA and published in the New England Journal of Medicine.

"We are very pleased with the CHMP’s decision which recommends abiraterone acetate plus prednisone / prednisolone in combination with ADT for use in adult patients with newly diagnosed high-risk metastatic hormone-sensitive prostate cancer. Janssen Oncology has played a significant role in transforming the way prostate cancer is treated so far and aims to continue this progress," said Dr. Ivo Winiger-Candolfi, Oncology Solid Tumor Therapy Area Lead, Janssen Europe, Middle East and Africa.

Abiraterone acetate plus prednisone / prednisolone has already been approved by the European Commission (EC) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated and of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.3

In the LATITUDE study, the safety profile of ADT in combination with abiraterone acetate plus prednisone was consistent with prior studies in patients with metastatic castration-resistant prostate cancer (mCRPC). Most common adverse events were elevated incidences of mineralocorticoid-related hypertension and hypokalemia in the ADT in combination with abiraterone acetate plus prednisone arm compared with ADT and placebos.4 The observed degrees of hypertension and hypokalemia were both medically manageable with antihypertensive medications and potassium supplements as needed, only rarely required treatment discontinuation, and seldom led to serious consequences.4

The CHMP’s Positive Opinion will now be reviewed by the European Commission, which has the authority to grant approval of the new indication.

-ENDS-

NOTES TO EDITORS

About high-risk metastatic hormone-sensitive prostate cancer (mHSPC)

Not all prostate cancer is the same. It ranges from cancer confined to the prostate gland to cancer that has spread outside of the prostate to the lymph nodes, bones, or other parts of the body. The extent or spread of prostate cancer determines its stage.5 Hormone-sensitive prostate cancer (HSPC) refers to a stage of the disease when the patient is still sensitive to treatment with ADT.6 Patients with newly diagnosed mHSPC, particularly with high-risk characteristics, have a poor prognosis. ADT plus docetaxel has shown improved outcomes in mHSPC when compared to ADT alone, but many patients are not candidates for docetaxel and may benefit from alternative therapy.7 Also, while the majority of patients initially start on ADT, it usually becomes less effective over time.8,9,10

About the LATITUDE Trial2

The Phase 3, multinational, multicentre, randomised, double-blind, placebo-controlled LATITUDE study enrolled 1,199 newly diagnosed patients with metastatic hormone-naïve prostate cancer (mHNPC) and was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada. A total number of 597 patients were randomised to receive ADT in combination with abiraterone acetate plus prednisone (n=597), while 602 patients were randomised to receive ADT and placebos (n=602). Patients included had high-risk mHNPC documented by positive bone scan or metastatic lesions at the time of diagnosis on computed tomography (CT) or magnetic resonance imaging (MRI). Additionally, patients had to have at least two of the three following high-risk factors associated with poor prognosis:2

Gleason score ≥8
≥3 bone lesions
presence of measurable visceral metastases
These results served the basis for Janssen’s Type II variation application submission to the European Medicines Agency (EMA), seeking to expand the existing marketing authorisation for abiraterone acetate plus prednisone or prednisolone to include the treatment of adult men with newly-diagnosed, high-risk metastatic hormone-sensitive prostate cancer (mHSPC). If approved, this will broaden the use of abiraterone acetate plus prednisone / prednisolone to include an earlier stage of prostate cancer than its current indications.

Overall, the safety profile of ADT in combination with abiraterone acetate plus prednisone was consistent with prior studies in patients with metastatic castration-resistant prostate cancer (mCRPC). Most common adverse events were elevated incidences of mineralocorticoid-related hypertension and hypokalemia in the ADT in combination with abiraterone acetate plus prednisone arm compared with ADT and placebos. The incidence rate of grade 3 or higher hypertension (20% vs. 10%) was greater than that observed in prior studies of abiraterone acetate in mCRPC patients. There were no serious sequelae from the increased rate of hypertension. The incidence of hypokalemia was higher than that reported in prior Phase 3 studies of abiraterone acetate plus prednisone in mCRPC; however, only two patients discontinued treatment due to hypokalemia and there were no hypokalemia-related deaths. Mineralocorticoid-associated adverse events were generally medically manageable.

About abiraterone acetate

Abiraterone acetate plus prednisone / prednisolone is the only approved therapy in mCRPC that inhibits production of androgens (which fuel prostate cancer growth) at all three sources that are important in prostate cancer – the testes, adrenals and the tumour itself.3,11,12

Indications3

In 2011, abiraterone acetate in combination with prednisone / prednisolone was approved by the European Commission (EC) for the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.

In December 2012, the EC granted an extension of the indication for abiraterone acetate permitting its use, in combination with prednisone or prednisolone, for the treatment of mCRPC, in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.3

Further Information3

The most common adverse reactions seen with abiraterone acetate plus prednisone / prednisolone include urinary tract infection, hypokalemia, hypertension, and peripheral oedema.

For a full list of side effects and for further information on dosage and administration, contraindications and other precautions when using abiraterone acetate plus prednisone / prednisolone please refer to the summary of product characteristics, which is available at: View Source