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FDA grants Roche’s TECENTRIQ® (atezolizumab) accelerated approval as initial treatment for certain people with advanced bladder cancer

On April 18, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) granted accelerated approval to TECENTRIQ (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy (Press release, Hoffmann-La Roche, APR 18, 2017, View Source [SID1234518604]). TECENTRIQ was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters and renal pelvis.

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"We are pleased that TECENTRIQ will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with a standard chemotherapy", said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "TECENTRIQ was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread."
The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition, based on early evidence suggesting clinical benefit. The indication for TECENTRIQ is approved under accelerated approval based on tumour response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Today’s approval of TECENTRIQ is based on the Phase II IMvigor210 study.

This is the third approval for TECENTRIQ in under a year in the US. TECENTRIQ is also approved for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities.

About the IMvigor210 study
IMvigor210 is an open-label, multicentre, single-arm Phase II study that evaluated the safety and efficacy of TECENTRIQ in people with locally advanced or metastatic urothelial carcinoma (mUC), regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. This accelerated approval is based on results from Cohort 1, which consisted of 119 people with locally advanced or mUC who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. People in this cohort received a 1200-mg intravenous dose of TECENTRIQ every three weeks until either unacceptable toxicity or disease progression. The primary endpoint of the study was objective response rate (ORR).

A summary of the efficacy data from the IMvigor210 study that supports this accelerated approval is included below.

The most common Grade 3–4 adverse reactions (≥ 2%) were: fatigue (8%), urinary tract infection (5%), anaemia (7%), diarrhoea (5%), increase in the level of creatinine in the blood (5%), intestinal obstruction (partial or complete blockage of the bowel), increase of the liver enzyme alanine transaminase (4%), hyponatraemia (low blood sodium level; 15%), decreased appetite (3%), sepsis (blood infection), back/neck pain (3%), renal failure and hypotension (low blood pressure). Five people (4.2%) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure or respiratory distress, which led to death. TECENTRIQ was discontinued for adverse reactions in 4.2% (5) of the 119 patients.

Roche is evaluating TECENTRIQ in a confirmatory Phase III study (IMvigor211), which compares TECENTRIQ to chemotherapy as initial treatment in people with a specific type of advanced bladder cancer and in people whose bladder cancer has progressed on at least one prior platinum-containing regimen.

About metastatic urothelial carcinoma
Metastatic urothelial cancer (mUC) is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advances for more than 30 years outside of the US. UC is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from UC, compared with women, and the disease is three times more common in developed countries than in less developed countries.

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ may also affect normal cells.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy (PCI)
The aim of personalised cancer immunotherapy (PCI) is to provide patients and physicians with treatment options tailored to the specific immune biology associated with a person’s individual tumour. The purpose is to inform treatment strategies that provide the greatest number of people with a chance for transformative benefit. PCI encompasses the search for reliable biomarkers that correlates with clinical benefit either as a monotherapy or in combination, along any of the seven steps in the cancer immunity cycle and across a broad range of tumour types. Fitting the right combination treatment strategies through immune biology profiling of the tumour, also known as phenotypes is one other way in which we are able to personalise treatments.The Roche PCI research and development programme comprises more than 20 investigational candidates, twelve of which are in clinical trials.
PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare. To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

Celgene in Asia-Pacific collab with Antengene, Tigermed as clinical support

On April 18, 2017 FierceBiotech reported in an article that Celgene is licensing rights to develop its TORC1/2 inhibitor CC-223 in East and Southeast Asia to Antengene (Article, FierceBiotech, APR 18, 2017, View Source [SID1234520281]). CRO Tigermed will help the latter with clinical development.

LION BIOTECHNOLOGIES HIGHLIGHTS PUBLICATION OF NEW TRANSLATIONAL DATA IN SCIENCE FOR TIL THERAPY FOR TREATMENT OF CERVICAL CANCER

On April 18, 2017 Lion Biotechnologies, Inc. (NASDAQ: LBIO), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that a publication in the journal Science provided new translational data from a clinical trial of TIL therapy for the treatment of advanced metastatic cervical cancer conducted at the Surgery Branch of the National Cancer Institute (NCI) (Press release, Lion Biotechnologies, APR 18, 2017, View Source [SID1234518616]). This trial has been supported in part by Lion under a Cooperative Research and Development Agreement (CRADA) with Dr. Steven Rosenberg, Chief of the Surgery Branch, National Cancer Institute (NCI), National Institutes of Health.

"Based on the encouraging data we have seen thus far for TIL therapy in this indication, we have initiated a Phase 2 trial of Lion’s TIL therapy in metastatic cervical cancer to investigate the responses seen in the NCI trial in a larger number of cervical cancer patients. However, patient selection in our ongoing Phase 2 trial is not limited by the presence of HPV, as the study is designed to allow a broader patient population to be enrolled," said Maria Fardis, PhD, MBA, President and Chief Executive Officer of Lion Biotechnologies.

Data from the NCI clinical trial was previously presented at the 2014 meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. These data indicated that a single infusion of TIL therapy generated two complete and durable remissions, ongoing at 15 and 22 months at the time of presentation. A third patient was reported to have achieved a partial three-month response with a 39% reduction in tumor volume.

The new translational study published in Science further evaluated the two patients with ongoing complete remissions. These data demonstrated that the antitumor activity of these patients’ TIL targeted both viral and non-viral tumor antigens.

Dr. Christian Hinrichs, the lead investigator of the trial at NCI’s Center for Cancer Research (CCR) said, "Our research shows the importance of not only viral but also non-viral antigens in immunotherapy for cervical cancer. These findings have important implications for how we design and study new treatments for this disease."

Johnson & Johnson Reports 2017 First-Quarter Results:

On April 18, 2017 Johnson & Johnson (NYSE: JNJ) reported sales of $17.8 billion for the first quarter of 2017, an increase of 1.6% as compared to the first quarter of 2016 (Press release, Johnson & Johnson, APR 18, 2017, View Source [SID1234518610]).

Operational sales results increased 2.0% and the negative impact of currency was 0.4%. Domestic sales increased 0.6%. International sales increased 2.8%, reflecting operational growth of 3.6% and a negative currency impact of 0.8%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.2%, domestic sales decreased 0.7% and international sales increased 3.4%.*

Net earnings and diluted earnings per share for the first quarter of 2017 were $4.4 billion and $1.61, respectively. First-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.4 billion. First-quarter 2016 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.2 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.0 billion and adjusted diluted earnings per share were $1.83, representing increases of 3.8% and 5.8%, respectively, as compared to the same period in 2016. * On an operational basis, adjusted diluted earnings per share also increased 7.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"Johnson & Johnson’s first-quarter results are in line with our expectations and we are confident we will achieve the full-year financial guidance we established at the beginning of the year," said Alex Gorsky, Chairman and Chief Executive Officer. "The pending acquisition of Actelion demonstrates our ongoing commitment to bringing innovation to patients with significant unmet needs, and provides a unique opportunity for us to expand our portfolio with leading, differentiated in-market medicines and promising late-stage products. We look forward to the associates from Actelion joining the Johnson & Johnson Family of Companies."

The Company is now including the estimated impact of the Actelion transaction in its financial guidance. As such, the Company increased its sales guidance for the full-year 2017 to $75.4 billion to $76.1 billion. Additionally, the Company increased its adjusted earnings guidance for full-year 2017 to $7.00 – $7.15 per share.*

Worldwide Consumer sales of $3.2 billion for the first quarter 2017 represented an increase of 1.0% versus the prior year, consisting of an operational increase of 0.8% and a positive impact from currency of 0.2%. Domestic sales increased 4.1%; international sales decreased 1.3%, which reflected an operational decrease of 1.6% and a positive currency impact of 0.3%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales decreased 2.3%, domestic sales decreased 2.9% and international sales decreased 1.9%*.

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were negatively impacted by LISTERINE oral care products, baby care products, and wound care products, partially offset by growth in over-the-counter products, including domestic TYLENOL analgesics.

Worldwide Pharmaceutical sales of $8.2 billion for the first quarter 2017 represented an increase of 0.8% versus the prior year with an operational increase of 1.4% and a negative impact from currency of 0.6%. Domestic sales decreased 1.3%; international sales increased 4.1%, which reflected an operational increase of 5.6% and a negative currency impact of 1.5%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.2%, domestic sales decreased 0.4% and international sales increased 6.1%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by new products and the strength of core products. Strong growth in new products include DARZALEX (daratumumab), for the treatment of patients with multiple myeloma and IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer. Additional contributors to operational sales growth included STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, and INVEGA SUSTENNA/XEPLION/TRINZA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults. Sales growth was negatively impacted by a positive adjustment of rebate accruals in the first quarter of 2016, which did not occur to the same degree in the first quarter of 2017.

During the quarter, the Company announced a definitive agreement to acquire Actelion Ltd., a leading biopharmaceutical company, for approximately $30 billion. The public tender offer for Actelion has been declared successful based on the number of shares tendered and regulatory approval has been obtained in six of seven jurisdictions in which the company filed for such approval, with antitrust approval from the European Commission pending. The transaction is expected to close in the second quarter of 2017, subject to the satisfaction of remaining closing conditions.

Also in the quarter, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion recommending broadening the existing marketing authorization for DARZALEX (daratumumab) for use in combination with lenalidomide and dexamethasone; or bortezomib and dexamethasone, for the treatment of multiple myeloma in patients who have received at least one prior therapy. A supplemental New Drug Application was submitted to the U.S. Food and Drug Administration for IMBRUVICA (ibrutinib) for the treatment of chronic Graft-Versus-Host Disease after failure of one or more lines of systemic therapy.

In April, subsequent to the quarter, a marketing authorization application was submitted to the European Medicines Agency for ZYTIGA (abiraterone acetate) to expand the existing indication to include treatment of men with newly diagnosed high-risk metastatic hormone sensitive prostate cancer.

Worldwide Medical Devices sales of $6.3 billion for the first quarter 2017 represented an increase of 3.0% versus the prior year consisting of an operational increase of 3.4% and a negative currency impact of 0.4%. Domestic sales increased 2.2%; international sales increased 3.8%, which reflected an operational increase of 4.7% and a negative currency impact of 0.9%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.7%, domestic sales decreased 0.2% and international sales increased 3.7%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by electrophysiology products in the Cardiovascular business; ACUVUE contact lenses in the Vision Care business and endocutters in the Advanced Surgery business, partially offset by declines in the Diabetes Care business.

During the quarter, the company completed the acquisition of Abbott Medical Optics, a wholly-owned subsidiary of Abbott and global leader in ophthalmic surgery, for approximately $4.3 billion.

Additionally, the acquisitions of Megadyne Medical Products, Inc., a privately held medical device company that develops, manufactures and markets electrosurgical tools, and Torax Medical Inc., a privately held medical device company that manufactures and markets the LINX Reflux Management System for the surgical treatment of gastroesophageal reflux disease, were completed.

In April, subsequent to the quarter, the acquisition of Neuravi Limited, a privately held medical device company that develops and markets medical devices for neurointerventional therapy, was completed.

XOMA Presents Positive Data from PTH1R Monoclonal Antibody Program

On April 18, 2017 XOMA Corporation (Nasdaq:XOMA), a pioneer in the discovery and development of therapeutic antibodies, reported the presentation of positive data from pre-clinical studies investigating the activity of its anti-PTH1R antagonist monoclonal antibody (mAb) (Press release, Xoma, APR 18, 2017, View Source [SID1234518611]). The antibody is a potential first-in-class therapeutic agent for the treatment of hyperparathyroidism (HPT) and humoral hypercalcemia of malignancy (HHM). These presentations were made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and the Endocrine Society (ENDO) annual meetings.

The PTH1R receptor is part of the B GPCR family and is the primary receptor of two ligands, parathyroid hormone (PTH) and parathyroid related protein (PTHrP). Hypercalcemia can occur when elevated levels of PTH, as seen in primary HPT, or elevated levels of PTHrP, as seen in HHM, lead to excessive activation of the PTH1R receptor. A potent and long-acting receptor antagonist could reverse hypercalcemia in all these conditions.

"Consistent with our new strategy, we are seeking partners with a deep commitment to and an expertise in drug development who are interested in licensing this first-in-class antibody and taking it through the clinical development process," said Jim Neal, Chief Executive Officer of XOMA. "There is a real need for better therapies that address hypercalcemia induced by hyperparathyroidism, and we are encouraged by these data, which demonstrate the efficacy of our anti-PTH1R approach as a potential treatment for patients suffering from HPT and HHM."

Data presented at the AACR (Free AACR Whitepaper) and ENDO conferences between April 1-4, 2017 showed:

PTH1R antagonism in vitro by the anti-PTH1R mAb translated to potent in vivo activity
XOMA’s anti-PTH1R antagonist mAb has the potential to become a first-in-class therapy for HHM, as the data demonstrated it ameliorated hypercalcemia and associated morbidities in pre-clinical models
XOMA’s antibody libraries enabled the discovery of functional antibodies against a very complex target — i.e. the G-Protein Coupled PTH1Receptor
A high affinity fully human mAb to PTH1R has been selected and characterized
Proprietary antibody engineering resulted in antibodies with improved potency and manufacturing characteristics
"While hyperparathyroidism is a classic endocrine disorder, HHM spans both endocrine and oncology specialties. HHM is a life-threatening complication of many advanced cancers and is caused by tumor secretion of the PTH1R ligand, PTH-related peptide, which causes high calcium. Since current treatments often fall short of correcting hypercalcemia and many cancer patients die from such high calcium and associated metabolic complications, PTH1R antibodies could prove beneficial for the treatment of this devastating condition," said John Wysolmerski, MD, Professor of Medicine and Associate Section Chief for Research in the Section of Endocrinology and Metabolism, Yale School of Medicine.

The complete presentations can be found online at www.xoma.com/content/pipeline/publications.htm.

About XOMA’s PTH1R Monoclonal Antibodies Program
XOMA has developed unique functional antibody antagonists targeting PTH1R, a G-protein-coupled receptor involved in the regulation of calcium metabolism. These antibodies have shown promising efficacy in in vivo studies and potentially could address high unmet medical needs, including primary hyperparathyroidism (PHPT) and humoral hypercalcemia of malignancy (HHM). Some secondary and tertiary HPT cases are additionally challenging to manage via current pharmacological approaches and may be well-addressed by XOMA’s anti-PTH1R antibody.