On August 1, 2017 Genomic Health, Inc. (NASDAQ: GHDX) reported financial results and business progress for the quarter ended June 30, 2017 (Press release, Genomic Health, AUG 1, 2017, View Source [SID1234519966]).

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Total revenue was $85.5 million in the second quarter of 2017, compared with $82.0 million in the second quarter of 2016, an increase of 4 percent, and an increase of 5 percent on a constant currency basis.i

U.S. product revenue was $72.4 million in the second quarter of 2017, compared with $69.6 million in the second quarter of 2016. U.S. invasive breast revenue from Oncotype DX Breast Recurrence Score test sales was $65.6 million in the second quarter of 2017, compared with $64.4 million in the second quarter of 2016. U.S. prostate revenue from Oncotype DX Genomic Prostate Score (GPS) test sales was $4.1 million in the second quarter of 2017, compared with $2.3 million in the second quarter of 2016.

International product revenue was $13.1 million in the second quarter of 2017, compared with $12.3 million in the second quarter of 2016, an increase of 6 percent, and an increase of 10 percent on a constant currency basis.i

"In the second quarter, we continued to deliver solid results reflecting both the strength and differentiation of our clinical data and unmatched commercial channel, generating a 9 percent increase in test volume and a 4 percent increase in revenue," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "Importantly, we delivered operating leverage and made significant progress toward our goal of delivering full-year profitability, having improved net loss by $9 million in the first half of the year."

More than 31,550 Oncotype test results were delivered in the second quarter of 2017, an increase of 9 percent, compared with more than 29,060 test results delivered in the same period in 2016. Oncotype DX Breast Recurrence Score tests delivered in the U.S. grew 5 percent and Oncotype DX Genomic Prostate Score tests delivered in the U.S. grew 38 percent compared with the second quarter of the prior year. International tests delivered grew 12 percent compared with the same period of the prior year and represented approximately 24 percent of total test volume in the second quarter of 2017.


Operating loss for the second quarter of 2017 improved to $3.1 million, compared with $5.1 million for the second quarter of 2016. Net loss was $2.7 million, or 8 cents per share, for the second quarter of 2017, compared with a net loss of $6.1 million, or 18 cents per share, for the second quarter of 2016. Basic and diluted net loss per share was $0.08 for the second quarter of 2017, compared with basic and diluted net loss per share of $0.18 for the second quarter of 2016.

Total revenue for the six months ended June 30, 2017 was $169.5 million compared with $162.9 million for the six months ended June 30, 2016, an increase of 4 percent. On a constant currency basis, revenue increased 5 percent compared with the same period in the prior year.i

International product revenue was $26.5 million for the six months ended June 30, 2017, compared with $22.7 million for the six months ended June 30, 2016, an increase of 16 percent, and an increase of 20 percent on a constant currency basis.i

Operating loss improved to $6.0 million for the six months ended June 30, 2017 compared with an operating loss of $13.9 million for the six months ended June 30, 2016. Net loss was $3.5 million for the six months ended June 30, 2017 compared with a net loss of $12.5 million for the six months ended June 30, 2016.

Cash and cash equivalents and short-term marketable securities at June 30, 2017 were $109.8 million, compared with $87.7 million at December 31, 2016 excluding the fair value of the company’s investment in a marketable security of $9.3 million.

2017 Financial Outlook

The company is providing the following adjusted financial guidance for the full year ending December 31, 2017:

·
Total revenue of between $345 to $355 million (formerly $355 to $370 million); and
·
Profit for the full-year at either end of revenue range (formerly profit at revenue above $362.5 million).

"While the timing of important reimbursement drivers has delayed the pace of revenue growth, we expect to deliver full-year profitability at these revised revenue levels, including double-digit revenue growth in the fourth quarter," said Brad Cole, chief operating officer and chief financial officer of Genomic Health. "We expect full-year CMS intermediate prostate coverage and the implementation of both PAMA reimbursement rates and AJCC staging criteria, along with increased global market penetration, to drive strong revenue growth in 2018."

Recent Business Highlights

·
Presented new results from a large, community-based, multi-center clinical validation study conducted at Kaiser Permanente at the American Urological Association (AUA) 2017 Annual Meeting. The results confirmed that the Oncotype DX GPS test is a strong independent predictor of prostate cancer-specific death and disease progression (metastases) at 10 years in men with localized prostate cancer.
·
Data from two Oncotype DX GPS test analyses based on a prospective, multi-center, 1,200-patient study were also presented at AUA, including results that represent the first-ever prospective validation of a tissue-based molecular marker in prostate cancer. The second analysis, presented at AUA and published online in Urology, reinforced that the GPS test significantly increases use of and persistence on active surveillance.
·
Initiated an early access Clinical Utility Program for select centers around the country in preparation for the commercial launch of the Oncotype DX AR-V7 Nucleus Detect test in collaboration with Epic Sciences.
·
The 15th St. Gallen International Breast Cancer Conference Expert Panel published updated guidelines endorsing the Oncotype DX Breast Recurrence Score test for guiding treatment decisions on adjuvant chemotherapy in both node-negative and node-positive patients (up to three nodes).

·
Breast Cancer Research and Treatment published positive five-year clinical outcome results from the PlanB study led by the West German Study Group (WSG) in 93 centers across Germany. The study showed that women with Recurrence Score results of 11 or less who were treated with hormonal therapy alone had excellent outcomes with 94 percent disease-free survival rates at five years despite having high-risk disease by traditional parameters.
·
Presented results from eight studies across breast, prostate and kidney cancers that provide additional evidence of the value of Oncotype DX tests in predicting clinically meaningful endpoints and outcomes across cancer types at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

On August 1, 2017 Exelixis, Inc. (NASDAQ:EXEL) reported that data from clinical trials of cabozantinib and cobimetinib will be the subject of 10 presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, September 8 – 12, 2017 (Press release, Exelixis, AUG 1, 2017, View Source [SID1234519965]).

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Progression-free survival by independent radiology review and updated overall survival results from CABOSUN, a randomized phase 2 clinical trial of cabozantinib compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), will be presented as a late-breaking abstract in the Genitourinary Tumours, Non-Prostate poster discussion session on Sunday, September 10. Final data from the phase 1 study of cabozantinib in combination with nivolumab with or without ipilimumab for the treatment of metastatic urothelial carcinoma and other genitourinary malignancies will be presented in the Genitourinary Tumours, Non-Prostate oral presentation session on Saturday, September 9. Additionally, poster presentations will detail the evaluation of cabozantinib in RCC and advanced penile squamous cell carcinoma, and of cobimetinib in combination studies in metastatic melanoma.

"We look forward to this year’s ESMO (Free ESMO Whitepaper) Congress where new data from the CABOSUN trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma will be presented, as well as the final analysis from the study exploring cabozantinib in combination with nivolumab and ipilimumab in genitourinary tumors, including metastatic urothelial carcinoma," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "The slate of data featuring Exelixis-discovered compounds demonstrates our commitment to advancing our ongoing clinical research program to help improve care and outcomes for patients with cancer."

Cabozantinib to be featured in eight presentations

The full schedule of cabozantinib presentations expected at the meeting is as follows:

Oral Presentation

[846O] "Final results of a phase I study of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus Ipilimumab (Ipi) in patients (pts) with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies"
Dr. Rosa Nadal, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
Session: Genitourinary Tumours, Non-Prostate
Oral presentation Saturday, September 9, 9:15 – 10:45 a.m. CEST, Madrid Auditorium
Note: This is a National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) study.

Poster Discussion

[LBA38] "Progression-free survival (PFS) by independent review and updated overall survival (OS) results from Alliance A031203 trial (CABOSUN): cabozantinib versus sunitinib as initial targeted therapy for patients (pts) with metastatic renal cell carcinoma (mRCC)"
Dr. Toni Choueiri, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 2:45 – 4:15 p.m. CEST, Cordoba Auditorium
Note: This is an NCI-CTEP study.

Poster Presentations

[872P] "Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib (C) vs everolimus (E) in advanced renal cell carcinoma (RCC)"
Dr. Thomas Powles, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London, England
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[876P] "Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): the Gustave Roussy experience"
Dr. Lisa Derosa, Gustave Roussy Institute of Oncology, Villejuif, France
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[891P] "Outcomes of patients with metastatic renal cell carcinoma (mRCC) who were treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitor (ICI) therapy"
Dr. A.Y. Shah, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[901P] "Safety and efficacy of cabozantinib for metastatic renal cell carcinoma (mRCC): real world data from an Italian Expanded Access Program (EAP)"
Dr. G. Procopio, Department of Medical Oncology, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milan, Italy
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[912P] "Cabozantinib for the treatment of patients with metastatic variant histology renal cell carcinoma (vhRCC): a retrospective study"
Dr. M.T. Campbell, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[927TiP] "Cabozantinib in patients with advanced penile squamous cell carcinoma (PSCC): the open-label, single-arm, single-center, phase 2, CaboPen trial"
Dr. A. Necchi, Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

Cobimetinib to be featured in two presentations

Also at the congress, Exelixis’ collaborator Genentech, a member of the Roche Group, will present data on cobimetinib, an Exelixis-discovered compound, in metastatic melanoma. The full schedule of cobimetinib presentations expected at the meeting is as follows:

Poster Discussion

[1225PD] "Prognostic impact of early complete metabolic response on FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with combination vemurafenib & cobimetinib"
Dr. Wen Xu, Peter MacCallum Cancer Centre, Melbourne, Australia
Session: Melanoma and Other Skin Tumours
Poster presented Monday, September 11, 11:00 a.m. – 12:15 p.m. CEST, Pamplona Auditorium

Poster Presentation

[1241P] "Impact of duration of response (DOR) on overall survival (OS) in patients with metastatic melanoma treated with dacarbazine (DTIC), vemurafenib (V), or cobimetinib plus vemurafenib (C+V): a pooled analysis"
Dr. Karl Lewis, University of Colorado Cancer Center, Aurora, Colorado, USA
Session: Melanoma and Other Skin Tumours
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

About the CABOSUN Study

On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment. CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These results were first presented by Dr. Toni Choueiri at the ESMO (Free ESMO Whitepaper) 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016).1 In June 2017, a blinded independent radiology review committee confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS.

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate or poor risk per the IMDC criteria (Heng, JCO, 2009).2 Prior systemic treatment for RCC was not permitted.

Please see Important Safety Information below and full U.S. prescribing information at View Source

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma (RCC) and urothelial carcinoma.3

The American Cancer Society’s 2017 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.4 Clear cell RCC is the most common type of kidney cancer in adults.5 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.6 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment, and an estimated 14,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.7

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.8 Urothelial carcinoma occurs mainly in older people, with 90 percent of patients aged 55 or older.9 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.9 In 2013, an estimated 587,426 people were living with bladder cancer in the U.S.10

About CABOMETYX (cabozantinib)

CABOMETYX is the tablet formulation of cabozantinib. Its targets include MET, AXL and VEGFR-1, -2 and -3. 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.

CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On April 25, 2016, the FDA approved CABOMETYX tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. 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 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. Ipsen has confirmed its intent to submit the regulatory dossier for cabozantinib as a treatment for first-line advanced renal cell carcinoma in the European Union in the third quarter of 2017.

On January 30, 2017, Exelixis and Takeda Pharmaceutical Company Limited announced an exclusive licensing agreement for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

CABOMEYX is not indicated for the treatment of previously untreated advanced RCC.

U.S. Important Safety Information

Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.

Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.

Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.

Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.

Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.

Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see full Prescribing Information at View Source

About the Cobimetinib and Vemurafenib Combination

Cobimetinib is a reversible inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK pathway) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50% of cases. Tumors with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor. About 50% of patients with BRAF mutation positive melanoma experience a tumor response when treated with a BRAF inhibitor, however development of resistance and subsequent tumor progression limits treatment benefit. Clinical and preclinical analyses indicated that reactivation of the MEK-ERK pathway may underlie development of resistance to BRAF inhibitors in many progressing tumors, and that co-treatment with a BRAF and MEK inhibitor delays the emergence of resistance in the preclinical setting, providing the rationale for testing the combination of vemurafenib and cobimetinib in clinical trials. The U.S. Food & Drug Administration approved cobimetinib for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib, in 2015. Cobimetinib is also being investigated in combination with several investigational and approved medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.

On August 1, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB), an oncology-focused, clinical stage biotechnology company (the "company"), reported the initiation of a collaboration with Avicenna Oncology GmbH, a leading precision medicine company based in Basel, Switzerland (Press release, Cellectar Biosciences, AUG 1, 2017, View Source [SID1234519964]). The collaboration will focus on the development of new phospholipid drug conjugates (PDCs) combining Cellectar’s patented phospholipid ether delivery platform with Avicenna’s novel cytotoxic payloads (potent anti-cancer small molecules).

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"We believe the combination of our targeted PDC delivery with Avicenna’s proprietary payloads has tremendous potential for the development of selective therapeutics for patients suffering with cancer," said Jim Caruso, president and CEO of Cellectar Biosciences. "This collaboration further validates the utility of our PDC delivery platform to provide targeted treatment of various resistant cancers, expands and accelerates our conjugate program research and potentially increases our novel, small molecule PDC pipeline."

Under the terms of the research collaboration, Avicenna will provide their novel payloads to Cellectar, which will leverage its expertise in chemical conjugation to link the molecules to its phospholipid ether (PDC platform). Cellectar will oversee the in vitro and in vivo testing of these molecules alongside an antibody drug conjugate (ADC) with the same payload. Both companies will have the option to advance the development of any of the newly conjugated molecules (PDCs). Financial terms of the collaboration have not been disclosed.

"There remains a significant unmet medical need for providing patients with new generations of targeted treatments with improved therapeutic index. Combining Cellectar’s PDC platform with our payloads is a very promising approach that could potentially overcome some of the disadvantages presently seen with ADCs," said Zaki Sellam, MSc, MBA, founder and CEO of Avicenna Oncology. "In line with our common vision, we are very excited to combine our collective expertise to potentially provide new treatment options for patients"

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

On August 1, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported financial and operating results for its second quarter ended June 30, 2017 (Press release, Foundation Medicine, AUG 1, 2017, View Source [SID1234519963]). Results and business highlights for the quarter included:

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Achieved second quarter revenue of $35.0 million, 24% year-over-year growth;
Reported 15,924 clinical tests in the second quarter, 55% year-over-year growth;
Submitted the final module to the FDA in June for FoundationOne CDx as part of the Parallel Review process with FDA and CMS;
Presented new data at the 2017 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) which continues to validate the clinical utility of Comprehensive Genomic Profiling (CGP) in guiding treatment towards targeted therapy, immunotherapy and clinical trials;
Announced a collaboration with ASCO (Free ASCO Whitepaper) to identify patients for its Targeted Agent and Profiling Utilization Registry (TAPUR) study;
Announced a collaboration with the National Cancer Institute (NCI) and ECOG-ACRIN Cancer Research Group to identify patients for NCI-Match (Molecular Analysis for Therapy Choice) study; and,
Published 29 manuscripts in high-quality, peer-reviewed journals and delivered 49 podium and poster talks at various medical and scientific meetings.
"Foundation Medicine delivered a strong second quarter, highlighted by record clinical volume and total revenue, increased adoption of our molecular information solutions by both clinicians and biopharma partners, and importantly, improved cancer care for the patients we serve," said Troy Cox, chief executive officer of Foundation Medicine. "In addition, we advanced the parallel review with FDA and CMS for FoundationOne CDx with the submission of our final module to the FDA in June, a significant milestone in the process. If approved, FoundationOne CDx would become the first pan-cancer universal companion diagnostic, a highly differentiated and valuable solution for patients, oncologists and biopharma partners."

Foundation Medicine reported total revenue of $35.0 million in the second quarter of 2017, compared to $28.2 million in the second quarter of 2016. Revenue from biopharmaceutical customers was $22.1 million in the second quarter of 2017, compared to $18.9 million in the second quarter of 2016. The results of 4,762 tests were reported to biopharmaceutical customers in this year’s second quarter.

Revenue from clinical testing in the second quarter of 2017 was $12.9 million, compared to $9.4 million in the second quarter of 2016. The company reported 15,924 tests to clinicians in the second quarter of 2017, a 55% increase from the same quarter last year. This number includes 12,442 FoundationOne tests, 1,608 FoundationOne Heme tests, 1,594 FoundationACT tests, and 280 FoundationFocus CDxBRCA tests.

Total operating expenses for the second quarter of 2017 were approximately $57.7 million, compared with $45.5 million for the second quarter of 2016. The increase in operating expenses was partially driven by investments in the company’s universal companion diagnostic assay, certain non-recurring cash and non-cash expenses, and investments in the company’s technology infrastructure. Net loss was approximately $44.3 million in the second quarter of 2017, or a $1.24 loss per share. At June 30, 2017, the company held approximately $71.5 million in cash, cash equivalents and marketable securities.

The company will now be reporting revenue in two components: Molecular Information Services and Pharma Research and Development Services. Molecular Information Services is revenue derived from commercially available platforms and services such as sample profiling, data access and SmartTrials, and includes revenue from both clinical and biopharma customers. Pharma Research and Development Services is revenue derived from work funded primarily by biopharma partners to develop new assays and other services. This new disclosure is intended to provide additional information related to the revenue and cost of revenue specifically related to the company’s commercially available platforms and services. During the second quarter, Molecular Information Services revenue was $30.3 million, including $12.9 million in revenue generated from our clinical customers, and $17.4 million in revenue generated from our biopharma customers. Pharma Research and Development Services revenue was $4.7 million.

On July 31st, Foundation Medicine entered into an agreement to expand its credit facility with Roche Finance from $100 million to $200 million. Any outstanding balance of the credit facility will convert to a term loan payable over a five-year period beginning on February 2, 2021. No funds were drawn under the credit facility at the time of the expansion. The company intends to use the proceeds to further fund product development, commercialization, corporate development initiatives and working capital.

2017 Outlook

Foundation Medicine’s business and financial outlook for 2017 is the following:

The company expects 2017 revenue will be in the range of $135 million to $145 million.
The company is increasing clinical volume guidance and now expects to deliver between 61,000 and 64,000 clinical tests in 2017.
The company is increasing operating expenses and now expects they will be in the range of $215 million and $225 million.
The company expects to advance its pan-cancer universal companion diagnostic assay, FoundationOne CDx, through the FDA and CMS Parallel Review process with a decision anticipated in the fourth quarter of 2017.
The company expects to continue reimbursement progress made in 2016 and pursue additional coverage decisions for its CGP assays.

On August 1, 2017 Celgene Corporation (NASDAQ:CELG) and Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) reported that IDHIFA (enasidenib) was granted approval from the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory AML (R/R AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA approved test (Press release, Celgene, AUG 1, 2017, View Source [SID1234519962]).1 IDHIFA, an oral targeted inhibitor of the IDH2 enzyme, is the first and only FDA-approved therapy for patients with R/R AML and an IDH2 mutation, which represents between 8 and 19 percent of AML patients.

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"The FDA approval of IDHIFA provides the first-ever treatment option for patients living with relapsed or refractory AML and an IDH2 mutation. We appreciate the FDA’s efforts to expedite the availability of IDHIFA for patients with this devastating disease weeks ahead of the PDUFA date," said Mark Alles, Chief Executive Officer of Celgene. "This milestone further illustrates the value of Celgene’s unique distributed research model. Our partnership with Agios is an exceptional example of how Celgene and its collaborators can positively impact the lives of patients with high unmet needs."

AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with more than 21,000 new cases estimated in the U.S. each year.4,5,6 The majority of patients with AML eventually experience relapse. Relapsed or refractory AML has a poor prognosis.6 For 8 to 19 percent of AML patients, the mutated IDH2 enzyme blocks normal blood cell development and results in an overabundance of immature blood cells.3

"The FDA approval of IDHIFA just four years after entering the clinic is the first of what we expect to be multiple first-in-class precision medicines for patients with cancer and rare genetic diseases from our productive discovery engine," said David Schenkein, M.D., Chief Executive Officer of Agios. "We look forward to working closely with Celgene to co-commercialize IDHIFA and provide access for patients in the U.S. with this devastating disease."

"AML is a complex, heterogeneous disease, which is particularly difficult to treat in the relapsed or refractory setting," said Martin Tallman, M.D., Hematologic Oncologist and Chief, Leukemia Service at Memorial Sloan Kettering Cancer Center. "IDH2 mutations inhibit the normal maturation of myeloid cells, so having a treatment that targets this mechanism is promising for patients and encouraging to us as physicians who have it as our goal to provide options for every patient."

Demonstrating Clinical Benefit & Safety with IDHIFA1

The FDA approval was based on the clinical data from an open-label, single-arm, multicenter, two-cohort clinical trial of adult patients with R/R AML and an IDH2 mutation (Study AG221-C-001, NCT01915498). IDHIFA was approved concurrently with the Abbott RealTime IDH2 companion diagnostic test, which is FDA-approved as an aid in identifying AML patients for treatment with IDHIFA.

The efficacy of IDHIFA was evaluated in 199 adult patients with R/R AML and an IDH2 mutation. IDH2 mutations were identified or confirmed by the Abbott RealTime IDH2 test. IDHIFA was given orally at a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed to manage side effects. Patients had a median age of 68 years (range of 19 to 100) and received a median of two prior anticancer regimens (ranging from one to six). More than half (52%) were refractory to previous therapy.

In this trial, IDHIFA demonstrated a combined complete response or complete response with partial hematologic improvement (CR/CRh) rate of 23% (n=46) (95% CI: 18%, 30%). Median duration of CR/CRh was 8.2 months (95% CI: range 4.3, 19.4). For patients who achieved a CR/CRh, the median time to first response was 1.9 months (range, 0.5 to 7.5 months) and the median time to best response of CR/CRh was 3.7 months (range, 0.6 to 11.2 months). Of patients achieving a CR/CRh, 85% (39 of 46 patients) did so within six months of initiating IDHIFA.

Among the 157 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 53 (34%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 42 patients who were independent of both RBC and platelet transfusions at baseline, 32 (76%) remained transfusion independent during any 56-day post-baseline period.

The safety of IDHIFA was evaluated in 214 patients with R/R AML and an IDH2 mutation. The median duration of exposure to IDHIFA was 4.3 months (range 0.3 to 23.6). The 30-day and 60-day mortality rates observed with IDHIFA were 4.2% (9/214) and 11.7% (25/214), respectively.

In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which can be fatal if not treated. IDHIFA can cause fetal harm if administered to pregnant women. The most common adverse reactions (≥20%) of any grade were nausea, vomiting, diarrhea, elevated bilirubin and decreased appetite. Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis, diarrhea, nausea, vomiting, decreased appetite, tumor lysis syndrome, and differentiation syndrome.

About IDHIFA

IDHIFA (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.

Important Safety Information


WARNING: DIFFERENTIATION SYNDROME
Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity:Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure
LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING

About Acute Myeloid Leukemia (AML)

AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to SEER, the median age of onset is 68.4 Some patients do not respond to chemotherapy and progress to relapsed/refractory AML.6 The five-year relative survival rate for AML is approximately 26.9% based on data from SEER 18 between 2007-2013.4 Overall survival for patients who become relapsed or refractory to initial therapy is estimated at less than six months.2,6 IDH2 mutations are present in about 8 to 19 percent of AML cases.3