On July 17, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that the U.S. Food and Drug Administration (FDA) has approved NERLYNX (neratinib), formerly known as PB272, a once-daily oral tyrosine kinase inhibitor for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy (Press release, Puma Biotechnology, JUL 17, 2017, View Source [SID1234519809]). Puma expects neratinib to become commercially available in September 2017 and to be marketed as NERLYNX.

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FDA approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Women (n=2,840) with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008).

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

"The fear of recurrence is ever present in the minds of most women with breast cancer, from the moment they are diagnosed to long after they finish adjuvant treatment," said Marisa C. Weiss, M.D., Chief Medical Officer and Founder of Breastcancer.org. "New and effective innovative therapeutic options provide huge hope to patients and their families, giving them a better chance of overcoming breast cancer with a chance for a full life."

"Despite advances in the treatment of early stage HER2-positive breast cancer, there remains a need for further therapeutic improvements in order to attempt to further reduce the risk of disease recurrence," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to be able to bring this new medicine to patients with breast cancer. We would like to express our appreciation to the patients, caregivers and physicians who contributed to the neratinib clinical development program and, more specifically, the ExteNET trial."

The full prescribing information for NERLYNX will be made available at WWW.NERLYNX.COM. The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first NERLYNX dose and continued during the first 2 cycles (56 days) of treatment and as needed thereafter. A Marketing Authorisation Application for neratinib is under review by the European Medicines Agency (EMA).

About HER2-Positive Breast Cancer
Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Indication
NERLYNX is a tyrosine kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Patient Support
Puma has developed the Puma Patient Lynx support program to provide patients and healthcare providers with assistance related to questions on accessing neratinib and referrals to resources that can help with reimbursement and financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or (1-855-816-5421).

Important Safety Information
There are possible side effects of NERLYNX. Patients must contact their doctor right away if they experience any of these symptoms. NERLYNX treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects.

Diarrhea
Diarrhea is a common side effect of NERLYNX. The diarrhea may be severe, and you may get dehydrated. Your healthcare provider should prescribe the medicine loperamide for you during your first 2 cycles (56 days) of NERLYNX and then as needed. To help prevent or reduce diarrhea:
· You should start taking loperamide with your first dose of NERLYNX.
· Keep taking loperamide during the first 2 cycles (56 days) of NERLYNX treatment and then as needed. Your healthcare provider will tell you exactly how much and how often to take loperamide.
· While taking loperamide, you and your healthcare provider should try to keep the number of bowel movements that you have at 1 or 2 bowel movements each day.
· Tell your healthcare provider if you have more than 2 bowel movements in 1 day, or you have diarrhea that does not go away.

Contact your healthcare provider right away if you have severe diarrhea or if you have diarrhea along with weakness, dizziness, or fever.

Liver Problems
Changes in liver function tests are common with NERLYNX. The patient’s doctor will do tests before starting treatment, monthly during the first 3 months, and then every 3 months as needed during treatment with NERLYNX. NERLYNX treatment may be stopped or the dose may be lowered if your liver tests show severe problems. Symptoms of liver problems may include tiredness, nausea, vomiting, pain in the right upper stomach-area (abdomen), fever, rash, itching, yellowing of your skin or whites of your eyes.

Pregnancy
Patients should tell their doctor if they are planning to become pregnant, are pregnant, plan to breastfeed, or are breastfeeding. NERLYNX can harm your unborn baby. Birth control should be used while a patient is receiving NERLYNX and for at least 1 month after the last dose. If patients are exposed to NERLYNX during pregnancy, they must contact their healthcare provider right away.

Common side effects in patients treated with NERLYNX
In clinical studies, the most common side effects seen in patients taking NERLYNX were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis (dry or inflamed mouth, or mouth sores), decreased appetite, muscle spasms, dyspepsia, changes in liver blood tests results, nail problems, dry skin, abdominal distention, weight loss, and urinary tract infection.

Patients should tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or View Source . Patients and caregivers may also report side effects to Puma Biotechnology at 1-844-NERLYNX (1-844-637-5969).
Please see Full Prescribing Information, available at www.NERLYNX.com .

On July 17, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported the company has initiated dosing in its Phase 1 clinical trial of FPA144, an anti-FGF receptor 2b antibody, in patients with advanced gastric and gastroesophageal cancer in Japan (Press release, Five Prime Therapeutics, JUL 17, 2017, View Source [SID1234519807]).

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"Gastric cancer is the sixth most common cancer by incidence globally and we estimate approximately 10% of gastric cancer patients have tumors that have FGFR2 gene amplification or overexpress FGFR2b, which are associated with significantly lower survival rates than the gastric cancer patient population as a whole," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "Moreover, the observed incidence of gastric cancer is higher in Asian populations than in other populations. We believe FPA144 represents a potentially promising treatment option for this targeted patient population with high unmet need."

The number of metastatic gastric and gastroesophageal junction cancer patients eligible for front-line treatment in Japan is approximately 73,000 patients per year. Five Prime estimates approximately 7,300 patients per year could be biomarker-positive and eligible for FPA144 treatment with front-line chemotherapy.

The Phase 1 open-label, dose-finding study will evaluate the safety, tolerability, pharmacokinetics (PK) and recommended dose of FPA144 in approximately 6 to 12 Japanese patients with advanced gastric or gastroesophageal cancer.

Completion of this Phase 1 trial is intended to enable the inclusion of Japanese patients in potential future Phase 3 trials of FPA144 in gastric cancer. Internal non-clinical data demonstrates additivity of FPA144 to standard-of-care chemotherapy regimens. Five Prime plans to initiate a global pivotal trial of FPA144 for front-line treatment of FGFR2b-overexpressing or FGFR2 gene-amplified metastatic gastric and gastroesophageal junction cancer in combination with chemotherapy in 2018.

About FPA144
FPA144 is an isoform-selective antibody in development as a targeted immuno-therapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b. FGFR2b overexpression and FGFR2 gene amplification are associated with poor prognosis.

FPA144 is currently being studied in a Phase 1 monotherapy trial evaluating the safety, PK and efficacy of biweekly 15 mg/kg infusions of FPA144 in patients with advanced gastric cancer whose tumors overexpress FGFR2b. Five Prime plans to initiate a combination trial of FPA144 with chemotherapy to advance into front-line therapy in the U.S. Five Prime retains global development and commercialization rights to FPA144.

On July 17, 2017 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported that data from the ongoing Phase 1 clinical study of flotetuzumab has been accepted for an oral presentation at the European Society for Medical Oncology Annual Congress, ESMO (Free ESMO Whitepaper) 2017, taking place in Madrid, Spain from September 8-12, 2017 (Press release, MacroGenics, JUL 17, 2017, View Source [SID1234519806]). The Phase 1 study (NCT02152956) is evaluating the safety and efficacy of flotetuzumab, a bispecific DART molecule that recognizes both CD123 and CD3, for the investigational treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

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MacroGenics will present the following oral presentation:
Title: Interim Results from a Phase 1 First-in-Human study of flotetuzumab, a CD123 x CD3 bispecific DART molecule, in AML/MDS
Date: September 10, 2017
Time: 11:00 CEST
Full session details and data presentation listings for ESMO (Free ESMO Whitepaper) 2017 Congress can be found at View Source

About Flotetuzumab
Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated in the U.S. and Europe in a Phase 1 dose-escalation study designed to assess the safety and tolerability of the molecule in patients with relapsed/refractory AML or MDS. MacroGenics retains full development and commercialization rights to flotetuzumab in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development and has rights to flotetuzumab in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the investigational treatment of AML.

On July 14, 2017 Amgen (NASDAQ:AMGN) reported the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and a variation to the marketing application to the European Medicines Agency (EMA) to include overall survival (OS) data from the Phase 3 head-to-head ENDEAVOR trial in the product information for KYPROLIS (carfilzomib) (Press release, Amgen, JUL 14, 2017, View Source [SID1234519801]).

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Data submitted to regulatory authorities showed that KYPROLIS, administered at the 56 mg/m2 dose as a 30-minute infusion twice weekly with dexamethasone (Kd56), reduced the risk of death by 21 percent over Velcade (bortezomib) and dexamethasone (Vd), resulting in a 7.6 month OS benefit (median OS 47.6 months for Kd56 versus 40.0 months for Vd, HR=0.79; p=0.01). The OS benefit was consistent regardless of prior bortezomib therapy (HR 0.75 for no prior Velcade; HR 0.84 for prior Velcade). These results were presented earlier this year at the 16th International Myeloma Workshop and the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

"KYPROLIS is the first-and-only multiple myeloma therapy to demonstrate superior overall survival in a head-to-head comparison with a current standard of care, extending survival by 7.6 months over Velcade," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We submitted these important data to regulatory authorities in the U.S. and Europe because we know that KYPROLIS may offer appropriate multiple myeloma patients a better chance for a longer life at first relapse compared to Velcade when added to dexamethasone."

Since its approval in 2012, KYPROLIS has been prescribed to more than 50,000 patients worldwide. The KYPROLIS clinical program continues to focus on providing solutions for physicians and patients in treating this frequently relapsing and difficult-to-treat cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

About ENDEAVOR
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kd56 versus Vd in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

Patients received treatment until progression with KYPROLIS as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For cycle one only, KYPROLIS was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 cycle one onwards. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of bortezomib. Eighty-two percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.