Synthon’s [vic-]trastuzumab duocarmazine (SYD985) granted FDA Fast Track designation for pre-treated HER2-positive metastatic breast cancer

On January 25, 2018 Synthon Biopharmaceuticals (‘Synthon’) reported that the U.S. Food & Drug Administration (FDA) has granted Fast Track designation for its investigational anti-HER2 antibody-drug conjugate (ADC) [vic-]trastuzumab duocarmazine (SYD985) (Press release, Synthon, JAN 25, 2018, View Source [SID1234523560]). This designation is for treating patients diagnosed with HER2-positive metastatic breast cancer (MBC) that has progressed during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease, or progressed during or after [ado-]trastuzumab emtansine treatment.

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U.S. FDA Fast Track designation is one of four programs that are intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life threatening condition.

Fast Track designation for [vic-]trastuzumab duocarmazine was granted based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial (SYD985.001). The positive clinical results indicate that this HER2-targeting ADC is efficacious and safe and could therefore provide substantial benefit to patients with no other treatment options.

In November 2017, Synthon initiated the pivotal Phase III TULIP trial, a multi-center, open-label, randomized clinical trial comparing the efficacy and safety of the ADC
[vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Patients are currently being enrolled in this trial, which will be conducted in up to 100 sites in the United States, Canada, Europe and Singapore.

Dr. Jacques Lemmens, chief executive officer of Synthon, commented: "We are very pleased with this Fast Track designation for [vic-]trastuzumab duocarmazine based on the promising Phase I data. There is a high unmet medical need in patients that have HER2-positive MBC and have progressed on trastuzumab and [ado-]trastuzumab emtansine. I believe that the benefit/risk balance of [vic-]trastuzumab duocarmazine is favorable and that it can provide extended benefit to these patients. Fast Track designation will support efficient development and review of [vic-]trastuzumab duocarmazine and enable early access of this promising new single-agent therapy option."

Generon Successfully Concludes First Phase III Clinical Trial of F-627 for Chemotherapy-induced Neutropenia

On January 25, 2018 Generon Corporation, an innovative biotech company in China developing novel biological therapeutics, reported that the first pivotal phase III study in the U.S. for F-627 to treat chemotherapy-induced neutropenia (CIN) in breast cancer patients met the primary endpoint (Press release, Generon (Shanghai), JAN 25, 2018, View Source [SID1234523559]). F-627 (Benegrastim / BineutaTM) is a recombinant human granulocyte colony-stimulating factor (rhG-CSF) dimer with a best-in-class potential to manage CIN in in cancer patients. The primary endpoint was to shorten the duration in days of grade 4 (severe) neutropenia in the first chemotherapy cycle. Patients treated with F-627 demonstrated significantly reduced duration of severe neutropenia compared to patents in placebo group (P<0.0001).

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"We are delighted to announce the significant results seen in this study. This is an important step toward completing the F-627 regulatory package for BLA (biological licensee application) submission" said Dr. David Lacey, Generon’s Chairman of Scientific Advisor board. "We are in the process of further analysis of the data, and plan to submit the results for presentation at an upcoming major medical meeting. " said Dr. Xiaoqiang Yan, Generon’s Chairman and CEO, adding, "Meeting the primary end point of the first pivotal study is an important milestone for Generon, demonstrating our ability to be an innovative biotech company on a global level."

This Phase III trial is a randomized, multi-center, double-blind, placebo controlled Phase III study of the efficacy and safety of a once-per-cycle dose of F-627 in women with stage II-IV breast cancer who are receiving myelotoxic TA chemotherapy treatment (Taxotere (docetaxel) + Adriamycin (doxorubicin)). Subjects were randomized to F-627 or Placebo at 2:1 ratio. About 24 hours after chemotherapy, subjects received either 20 mg fixed dose F-627 or Placebo. The subjects’ absolute neutrophil count (ANC) was measured each day post chemotherapy administration until ANC levels exceeded 2.0 x 109/L, then the ANC value was determined every three days until the next chemotherapy cycle. This is one of two pivotal Phase III studies required for BLA submission in the US. The second Phase III study is under an SPA with the FDA and currently ongoing.

The management executives of Yifan Pharmaceuticals congratulated Generon’s team on this achievement and emphasized their continued confidence in Generon’s ability to pursue F-627’s clinical development toward a successful BLA submission, and to bring the best-in-class rhG-CSF to patients worldwide.

Chemotherapy-induced Neutropenia (CIN)

CIN occurs commonly during current cancer treatments involving cytotoxic chemotherapy. In the U.S. alone, it is estimated that approximately 1.7 million cancer patients receive chemotherapy treatment, which amounts to a total of 7.5 million chemotherapy cycles performed annually with approximately 5.0 million chemotherapy cycles involving CIN. The global CIN market is estimated to be at $7.0 billion with about >85% of patients still on first-generation of rhG-CSFs, and less than 15% of patients using second-generation rhG-CSFs, the pegylated rhG-CSF.

About F-627

F-627 (benegrastim) is under development for the treatment of CIN in cancer patients. F-627 is a recombinant fusion protein containing G-CSF and human IgG2-Fc and is expressed in Chinese Hamster Ovary (CHO) cells. F-627 has an immunoglobulin-like structure. It consists of two G-CSF molecules at the N-terminal of Fc fragments (a G-CSF dimer). G-CSF is a growth factor acting on the neutrophilic lineage in the hematopoietic system. G-CSF binds to specific G-CSF receptors (G-CSFR) on the cell surface and stimulates differentiation, proliferation, and activation of neutrophilic granulocytes. F-627 has showed stronger bioactivities than the monomeric rhG-CSFs in vitro and in vivo.

Teva to Host Conference Call to Discuss Fourth Quarter and Full Year 2017 Financial Results at 8 a.m. ET on February 8, 2018

On January 25, 2018 Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) reported that it will issue a press release on its fourth quarter and full year 2017 financial results on Thursday, February 8, 2018 at 7:00 a.m. ET (Press release, Teva, JAN 25, 2018, View Source;p=RssLanding&cat=news&id=2328502 [SID1234523581]). Following the release, Teva will conduct a conference call and live webcast on the same day, at 8:00 a.m. ET.

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In order to participate, please dial the following numbers (at least 10 minutes before the scheduled start time): United States 1-866-869-2321; Canada 1-866-766-8269 or International +44(0) 203 0095710; passcode: 5279244. For a list of other international toll-free numbers, click here.

A live webcast of the call will also be available on Teva’s website at: www.ir.tevapharm.com. Please log in at least 10 minutes prior to the conference call in order to download the applicable audio software.

Following the conclusion of the call, a replay of the webcast will be available within 24 hours on the Company’s website. The replay can also be accessed until March 8, 2018, 9:00 a.m. ET by calling United States 1-866-247-4222; Canada 1-866-878-9237 or International +44(0) 1452550000; passcode: 5279244.

Myriad to Announce Fiscal Second-Quarter 2018 Financial Results on February 6, 2018

On January 25, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN) reported that it will hold its fiscal second-quarter 2018 sales and earnings conference call with investors and analysts at 4:30 p.m. ET on Tuesday, February 6, 2018 (Press release, Myriad Genetics, JAN 25, 2018, View Source [SID1234523579]). During the call, Mark C. Capone, president and CEO and Bryan Riggsbee, CFO, will provide an overview of Myriad’s financial performance for the fiscal second-quarter and provide a business update.

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To listen to the call, interested parties in the United States may dial 800-699-0623 or +1 303-223-4362 for international callers. All callers will be asked to reference reservation number 21879835. The conference call also will be available through a live webcast and a slide presentation pertaining to the earnings call will also be available under the investor section of our website at www.myriad.com. A replay of the call will be available two hours after the end of the call for seven days and may be accessed by dialing 800-633-8284 within the United States or +1 402-977-9140 for international callers and entering reservation number 21879835.

Janssen to Present 14 Abstracts in Prostate and Urothelial Cancers at ASCO GU 2018, Including New Data on Apalutamide (ARN-509), ZYTIGA® (abiraterone acetate) and Erdafitinib

On January 25, 2018 – New data from the Janseen Pharmaceutical Companies of Johnson & Johnson will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) 2018 Cancers Symposium taking place February 8-10 in San Francisco (Press release, Johnson & Johnson, JAN 25, 2018, View Source [SID1234523578]). In total, 14 company-sponsored abstracts with data for both investigational and approved compounds have been accepted for presentation, including for apalutamide and ZYTIGA (abiraterone acetate) in prostate cancer, and for erdafitinib in urothelial cancer. Most notably, Phase 3 data results from the SPARTAN clinical trial, assessing apalutamide in non-metastatic castration-resistant prostate cancer, will be featured as part of the Prostate Cancer Oral Abstract Session on Thursday, February 8.

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"New data featuring approved and investigational compounds continue to demonstrate our commitment to developing novel agents in areas of significant unmet medical need," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors at Janssen Research & Development, LLC. "We are especially excited to present results from the pivotal SPARTAN clinical trial with apalutamide in patients with non-metastatic castration-resistant prostate cancer during this important oncology meeting."

Key company-sponsored data presentations include:

Apalutamide:

SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) vs placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) (Abstract #161)
These data will be presented in Oral Abstract Presentation during Session A of the Prostate Cancer Program from 1:00 pm – 2:30 pm PST on Thursday, February 8th
ZYTIGA:

Abiraterone acetate (AA) plus prednisone (P) 5 mg QD in metastatic castration-naïve prostate cancer (mCNPC): Detailed safety analyses from the LATITUDE phase 3 trial (Abstract #182)
These data will be presented in Poster Presentation Session A from 11:30 am – 1:00 pm and 5:15 pm – 6:15 pm PST on Thursday, February 8th
Medical resource utilization (MRU) of abiraterone acetate plus prednisone (AAP) added to androgen deprivation therapy (ADT) in metastatic castration-naive prostate cancer: Results from LATITUDE (Abstract #201)
These data will be presented in Poster Presentation Session A from 11:30 am – 1:00 pm and 5:15 pm – 6:15 pm PST on Thursday, February 8th
Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (P) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC); Subgroup analysis of LATITUDE trial (Abstract #286)
These data will be presented in Poster Session B from 12:15 pm – 1:45 pm and 6:00 pm – 7:00 pm PST on Friday, February 9th
Erdafitinib:

Erdafitinib (ERDA; JNJ-42756493), a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRa): phase 2 continuous versus intermittent dosing (Abstract #411)
These data will be presented in Rapid Fire Abstract Session during the Urothelial Carcinoma Program from 6:00 pm – 7:00 pm PST on Friday, February 9th
A full list of company-sponsored abstracts to be presented at the meeting follows below:

Abstract No.

Title

Date/Time

Apalutamide

Abstract #161

SPARTAN, a phase 3 double-blind, randomized study of apalutamide (APA) vs placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC)

Oral Abstract Session A

Thursday, February 8th

1:00 pm – 2:30 pm PST

Abstract #27

Association of prostate-specific antigen (PSA) trajectories with risk for metastasis and mortality in non-metastatic castration-resistant prostate cancer (nmCRPC)

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

ZYTIGA

Abstract #182

Abiraterone acetate (AA) plus prednisone (P) 5 mg QD in metastatic castration-naïve prostate cancer (mCNPC): Detailed safety analyses from the LATITUDE phase 3 trial

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

Abstract #201

Medical resource utilization (MRU) of abiraterone acetate plus prednisone (AAP) added to androgen deprivation therapy (ADT) in metastatic castration-naive prostate cancer: Results from LATITUDE

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

Abstract #196

Real-world evidence in patient-related outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate plus prednisone (AA+P)

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

Abstract #200

Indirect treatment comparison (ITC) of abiraterone acetate (AA) plus prednisone (P) and docetaxel (DOC) on patient-reported outcomes (PROs) in metastatic castration-naïve prostate cancer (mCNPC)

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

Abstract #217

Neuropsychiatric adverse events of abiraterone acetate and enzalutamide: meta-analysis of randomized clinical trials with real world reporting patterns from EudraVigilance

Poster Session A

Thursday, February 8th

11:30 am – 1:00 pm
and 5:15 pm – 6:15 pm PST

Abstract #286

Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (p) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC); Subgroup analysis of LATITUDE Trial

Poster Session B
Friday, February 9th
12:15 pm – 1:45 pm and 6:00 pm – 7:15 pm PST

Abstract #296

Real-world study of enzalutamide and abiraterone acetate (with prednisone) tolerability (REAAcT) – results

Poster Session B

Friday, February 9th

12:15 pm – 1:45 pm
and 6:00 pm – 7:15 pm PST

Abstract #320

Real world patterns of treatment sequencing in Canada for metastatic castrate-resistant prostate cancer

Poster Session B

Friday, February 9th

12:15 pm – 1:45 pm
and 6:00 pm – 7:15 pm PST

Abstract #321

Patterns of prostate cancer management across Canadian prostate cancer treatment specialists

Poster Session B

Friday, February 9th

12:15 pm – 1:45 pm
and 6:00 pm – 7:15 pm PST

Abstract #343

Evolution of neuropsychiatric adverse events of abiraterone acetate and enzalutamide treatments reported in EudraVigilance, in metastatic castration resistant prostate cancer patients

Poster Session B

Friday, February 9th

12:15 pm – 1:45 pm
and 6:00 pm – 7:15 pm PST

Erdafitinib

Abstract #411

Erdafitinib (ERDA; JNJ-42756493), a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRa): Phase 2 continuous versus intermittent dosing

Rapid Fire Abstract Session
(Oral Abstract Presentation)

Friday, February 9th

6:00 pm – 7:00 pm PST

Abstract #450

Efficacy of programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) inhibitors in patients with FGFR mutations and gene fusions: Results from a data analysis of an ongoing phase 2 study of erdafitinib (JNJ-42756493) in patients (pts) with advanced urothelial cancer (UC)

Poster Session B

Friday, February 9th

12:15 pm – 1:45 pm
and 6:00 pm – 7:15 pm PST

About ZYTIGA
ZYTIGA (abiraterone acetate) is indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). ZYTIGA blocks CYP17-mediated androgen production, which fuels prostate cancer growth, at three sources: in the testes, adrenals and the prostate tumor tissue.

Since its first approval in the U.S. in 2011, ZYTIGA has been approved in combination with prednisone/prednisolone in 105 countries. More than 330,000 men worldwide, including 113,000 in the U.S., have received treatment with it, and it was the number one prescribed oral medication in the U.S. for men with mCRPC in 2016.

For more information about ZYTIGA, visit www.ZYTIGA.com.

Important Safety Information – ZYTIGA

CONTRAINDICATIONS – ZYTIGA (abiraterone acetate) is not indicated for use in women. ZYTIGA can cause fetal harm (Pregnancy Category X) when administered to a pregnant woman and is contraindicated in women who are or may become pregnant.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess – Use with caution in patients with a history of cardiovascular disease or with medical conditions that might be compromised by increases in blood pressure, hypokalemia, or fluid retention. ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Safety has not been established in patients with LVEF <50% or New York Heart Association (NYHA) Class III or IV heart failure (in Study 1) or NYHA Class II to IV heart failure (in Study 2) because these patients were excluded from these randomized clinical trials. Control hypertension and correct hypokalemia before and during treatment. Monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly.

Adrenocortical Insufficiency (AI) – AI was reported in patients receiving ZYTIGA in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Use caution and monitor for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity – In post-marketing experience, there have been ZYTIGA-associated severe hepatic toxicities, including fulminant hepatitis, acute liver failure and deaths. Monitor liver function and modify, withhold, or discontinue ZYTIGA dosing as recommended (see Prescribing Information for more information). Measure serum transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment, and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function. Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN.

Permanently discontinue ZYTIGA for patients who develop a concurrent elevation of ALT greater than 3X ULN and total bilirubin greater than 2X ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

Adverse Reactions – The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection and contusion.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT and hypokalemia.

Drug Interactions – Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA. Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA.

Use in Specific Populations – Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C).

About Apalutamide (ARN-509)
Apalutamide is an investigational, next-generation oral androgen receptor inhibitor that blocks the androgen signaling pathway in prostate cancer cells, and prevents binding of androgen to the androgen receptor and translocation of the androgen receptor to the nucleus of the cancer cell.

About Erdafitinib
Erdafitinib is a pan-fibroblast Growth Factor Receptor (FGFR) tyrosine kinase inhibitor currently being evaluated by Janssen in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer. Additional research is also being conducted to explore the use of erdafitinib in other cancer indications.