On 16 October, 2017 Ipsen (Euronext: IPN; ADR: IPSEY) and its partner Exelixis (NASDAQ: EXEL) reported that its global phase 3 CELESTIAL trial met its primary endpoint of overall survival (OS), with cabozantinib providing a statistically significant and clinically meaningful improvement in median OS compared to placebo in patients with advanced hepatocellular carcinoma (HCC) (Press release, Ipsen, OCT 16, 2017, View Source [SID1234520945]). The independent data monitoring committee for the study recommended that the trial should be stopped for efficacy following review of the second planned interim analysis. CELESTIAL is a randomized, global phase 3 trial of cabozantinib versus placebo in patients with advanced HCC who have been previously treated with sorafenib. The safety data in the study were consistent with the established profile of cabozantinib.

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In line with and in collaboration with our partner Exelixis, Ipsen expects to file in the first half of 2018 a variation of the initial application to the EMA and other relevant regulatory agencies and to evaluate potential next steps in the development strategy for cabozantinib outside the United States and Japan as a treatment for advanced HCC in patients who have been previously treated. Detailed results from CELESTIAL will be submitted for presentation at a future medical conference.

Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen, said: "Liver cancer is one of the leading causes of cancer deaths worldwide and more effective treatment options are urgently needed. We are pleased to report that in the CELESTIAL clinical study cabozantinib has been shown to provide a survival benefit and therefore has the potential to bring a new oral systemic treatment to previously treated patients with advanced liver cancer. "

About the CELESTIAL Study

CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who previously received sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017, and 773 patients were ultimately randomized. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms.

The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.

About HCC

Hepatocellular Carcinoma (HCC) is the most common form of liver cancer in adults.1 The disease originates in cells called hepatocytes found in the liver. With approximately 800’000 new cases diagnosed each year, HCC is the sixth most common cancer and the second-leading cause of cancer deaths worldwide.2,3 According to the GLOBOCAN data, it is estimated that across the European Union (EU-28) nearly 60’000 new patients will be diagnosed with liver cancer in 2020.4 Without treatment, patients with the disease in advanced stage usually survive between 4 and 8 months.5

About CABOMETYX (cabozantinib)

Cabometyx is an oral small molecule inhibitor of receptors, including VEGFR, MET, AXL and RET. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On April 25, 2016, the FDA approved Cabometyx tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy and on September 9, 2016, the European Commission approved Cabometyx tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Cabometyx is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

Ipsen also submitted to European Medicines Agency (EMA) the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on September 8, 2017, Ipsen announced that the EMA validated the application.

Cabozantinib is not approved for the treatment of advanced hepatocellular carcinoma.

On October 16, 2017 Fennec Pharmaceuticals Inc. (NASDAQ: FENC, TSX: FRX), a specialty pharmaceutical company focused on the development of PEDMARKTM (a unique formulation of sodium thiosulfate (STS)) for the prevention of platinum-induced ototoxicity in pediatric patients, reported data from its Phase 3 SIOPEL 6 study presented during the late breaker session on Saturday, October 14, 2017 at SIOP 2017 in Washington, DC (Press release, Fennec Pharmaceuticals, OCT 16, 2017, View Source [SID1234520965]).

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Top Line Efficacy Data

The SIOPEL 6 study met its primary endpoint. The study demonstrated that the addition of STS significantly reduces the incidence of cisplatin-induced hearing loss without any evidence of tumour protection. Among the 99 evaluable patients, hearing loss occurred in 30/45=67% treated with Cisplatin (Cis) alone and in 20/54=37.0% treated with Cis+STS, corresponding to a relative risk of 0.56(P=0.0033).

Fennec plans to pursue regulatory approval for PEDMARKTM based on the data from the SIOPEL 6 study along with the proof of principle data from COG ACCL0431. STS has received Orphan Drug Designation in the US in this setting and plans to pursue European Market Exclusivity for Pediatric Use upon approval.

"I am absolutely delighted that after 30 years of research we have found a safe way to reduce ototoxicity in children receiving platinum containing chemotherapy," said Penelope Brock, M.D., PhD, International Chair of SIOPEL. "This means that children who are cured from cancer after receiving platinum treatment can look forward to a normal healthy life, fully integrated into society. I believe this marks a new standard of care in pediatric oncology."
The Company also reported top-line data for secondary endpoints Event Free Survival (EFS) and Overall Survival (OS). The combination of Cis+STS was generally well tolerated. With a follow up of 52 months, 3yr EFS is Cis 78.8% and Cis+STS 82.1%; 3yr OS is Cis 92.3% and Cis+STS 98.2%.

"We are very pleased with the results of this study," stated Rosty Raykov, CEO of Fennec. " We would like to thank all the patients and their families who participated in this trial, physicians, the entire SIOPEL 6 team, and Dr. Neuwelt and his research team at OHSU. We believe that if approved PEDMARK would be an important therapy for patients and caregivers where currently there are no treatment options."

Safety and Tolerability

In the study, the results presented showed that treatment was well tolerated and acute toxicity similar and expected between arms. The table below presents the toxicities of the two arms:

Adverse event Grade CIS CIS+STS
N % N %
Febrile neutropenia 3 7 13.5 5 8.8
4 - - - -
Infection 3 5 9.6 6 10.5
4 - - - -
Hypomagnesemia 3 1 1.9 1 1.8
4 - - - -
Hypernatremia 3 - - 1 1.8
4 - - - -
Vomiting 3 1 1.9 3 5.3
4 - - - -
Nausea 3 3 5.8 2 3.5
4 - - - -

SIOP 2017 Presentation

Fennec will provide access to the recording of SIOP 2017 late breaker presentation on the Company’s website.

To access the archived recording, visit the Fennec website at www.fennecpharma.com.

SIOPEL 6

SIOPEL 6 is a multi-centre open label randomized phase 3 study evaluating the efficacy of STS in reducing ototoxicity in patients receiving cisplatin monotherapy for standard risk hepatoblastoma. From the beginning of 2007 to the end 2014, 52 sites from 11 countries enrolled 113 evaluable patients. The study is closed to recruitment and all protocol pre-specified IDMC safety reviews are now complete. The primary efficacy hearing endpoint analysis can be performed once patients have reached 3.5 years of age and an audiometry test can be carried out. The SIOPEL 6 study trial was designed with 80% power and a 5% significance level to detect an absolute 25% reduction in the rate of Brock grade ≥1 hearing loss with a chi-square test, from a 60% hearing loss in Cis alone arm to a 35% hearing loss in Cis+STS arm. The primary endpoint is the rate of Brock grade ≥ 1 hearing loss determined after the end of treatment at the age of ≥3.5 years by pure tone audiometry.

About PEDMARKTM (sodium thiosulfate/STS)

Cisplatin and other platinum compounds are essential chemotherapeutic components for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity in many patients, and are particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe there is estimated that over 7,000 children are diagnosed with local cancers that may receive platinum-based chemotherapy. Localized cancers that receive platinum agents may have overall survival rates of greater than 80% further emphasizing the quality of life after treatment. The incidence of hearing loss in these children depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

STS has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies are closed to recruitment. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors. COG ACCL0431 final results were published in the Lancet Oncology.

In May 2017, Fennec announced the launch of a Named Patient Program in Europe. European based Healthcare Professionals can obtain details about STS Named Patient Program by emailing [email protected].

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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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 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