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FDA APPROVES GARDASIL 9 FOR PREVENTION OF CERTAIN CANCERS CAUSED BY FIVE ADDITIONAL TYPES OF HPV

On 10 December, 2014 the USA Food and Drug Administration (FDA) approved Gardasil 9 (Human papillomavirus 9-valent Vaccine, Recombinant) for the prevention of certain diseases caused by nine types of Human Papillomavirus (HPV). Covering nine HPV types, five more HPV types than Gardasil (previously approved by the FDA), Gardasil 9 has the potential to prevent approximately 90% of cervical, vulvar, vaginal and anal cancers (Press release, US FDA, DEC 10, 2014, View Source [SID1234607427]).

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Gardasil 9 is a vaccine approved for use in females ages 9 through 26 and males ages 9 through 15. It is approved for the prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16, 18, 31, 33, 45, 52 and 58, and for the prevention of genital warts caused by HPV types 6 or 11. Gardasil 9 adds protection against five additional HPV types—31, 33, 45, 52 and 58— which cause approximately 20% of cervical cancers and are not covered by previously FDA-approved HPV vaccines.

"Vaccination is a critical public health measure for lowering the risk of most cervical, genital and anal cancers caused by HPV," said Dr Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research. "The approval of Gardasil 9 provides broader protection against HPV-related cancers."

A randomised, controlled clinical study was conducted in the USA and internationally in approximately 14,000 females ages 16 through 26 who tested negative for vaccine HPV types at the start of the study. Study participants received either Gardasil or Gardasil 9. Gardasil 9 was determined to be 97% effective in preventing cervical, vulvar and vaginal cancers caused by the five additional HPV types (31, 33, 45, 52, and 58). In addition, Gardasil 9 is as effective as Gardasil for the prevention of diseases caused by the four shared HPV types (6, 11, 16, and 18) based on similar antibody responses in participants in clinical studies.

Due to the low incidence of anal cancer caused by the five additional HPV types, the prevention of anal cancer is based on Gardasil’s demonstrated effectiveness of 78% and additional data on antibodies in males and females who received Gardasil 9.

The effectiveness of Gardasil 9 in females and males ages 9 through 15 was determined in studies that measured antibody responses to the vaccine in approximately 1,200 males and 2,800 females in this age group. Their antibody responses were similar to those in females 16 through 26 years of age. Based on these results, the vaccine is expected to have similar effectiveness when used in this younger age group.

Gardasil 9 is administered as three separate shots, with the initial dose followed by additional shots given two and six months later. For all of the indications for use approved by the FDA, Gardasil 9’s full potential for benefit is obtained by those who are vaccinated prior to becoming infected with the HPV strains covered by the vaccine.

The safety of Gardasil 9 was evaluated in approximately 13,000 males and females. The most commonly reported adverse reactions were injection site pain, swelling, redness, and headaches.

Gardasil 9 is manufactured by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., based in Whitehouse Station, New Jersey.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Avanir has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission .

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Three new companies join Cancer Research UK-Abcodia collaboration to identify blood markers for early cancer detection

On December 10, 2014 marker companies have been reported to work with the Early Diagnosis Consortium, a collaboration between Cancer Research UK, its commercial arm, Cancer Research Technology, and Abcodia, a specialist company engaged in the validation of biomarkers for the early detection and screening of cancer (Press release, Cancer Research Technology, DEC 10, 2014, View Source [SID1234523216]).

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The decision follows completion of a pilot phase to evaluate leading technologies for their ability to discover biomarkers that can detect cancer in its earliest stages, long before symptoms appear, when treatment is most likely to be effective. The technologies were tested against serum samples selected from a biobank of more than five million serum samples, collected from women as part of the UKCTOCS trial*, to which Abcodia has exclusive commercial access.

Based on these findings, the three companies involved will be Caprion which specialises in proteomics, Asuragen which uses next-generation sequencing to find circulating microRNAs, and the AIT Austrian Institute of Technology using its tumour auto-antibodies platform.

This next stage of the programme will focus on identifying biomarkers for colorectal, lung, oesophageal and pancreatic cancers, chosen because of the limited availability of screening tests for these cancers and patients’ poor survival when diagnosed at a late stage.

Dr Julie Barnes, chief executive of Abcodia, said: "We are excited to work with these world leading companies to bring their cutting edge technology to this endeavour. The application of such technologies to biomarker discovery in longitudinal samples donated before the clinical presentation of cancer is a real innovation and has the potential to make a real difference to the field of early cancer detection."

Professor Ian Jacobs, vice president at the University of Manchester, principal investigator of UKCTOCS and one of the founders of Abcodia, said: "Cancers that are diagnosed at a later stage are much more difficult to manage, so I am delighted to see the progress that this consortium is making. The experiments aimed at identifying biomarkers that could form simple, non-invasive tests for early cancer detection represent an ideal use of the biobank developed through UKCTOCS."

Dr Keith Blundy, chief executive of Cancer Research Technology, said: "After a successful pilot, we are delighted to be able to bring additional technological capability into this collaborative effort, to add to the clinical, scientific and commercial expertise of existing partners. The biobank derived from UKCTOCS is providing us with the opportunity, through this initiative, to potentially unlock a future in which thousands of cancer cases could be detected and treated before symptoms emerge."

Immunovaccine Receives FDA Fast Track Designation for DPX-Survivac for Treatment of Ovarian Cancer

On December 10, 2014 Immunovaccine reported that DPX-Survivac, the Company’s lead cancer vaccine candidate, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) as maintenance therapy in subjects with advanced ovarian, fallopian tube, and peritoneal cancer who have no measureable disease following surgery and front-line platinum/taxane chemotherapy to improve their progression-free survival (Press release Immunovaccine, DEC 10, 2014, View Source [SID:1234501175]). Ovarian cancer patients who have no measurable disease following their initial standard surgery and chemotherapy treatments have an unmet need that may be served by the DPX-Survivac therapy. DPX-Survivac is designed to activate T cells of the immune system that are expected to recognize and eliminate cancer cells in an attempt to keep patients in remission longer.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs with the potential to treat serious or life-threatening conditions and address an unmet medical need. This designation provides companies the opportunity for more frequent interactions with FDA during clinical development and the “rolling” submission of individual sections of a Biologics License Application (BLA) as they are completed for review by FDA. Additionally, therapies with Fast Track designation are eligible for priority review and/or accelerated approval, which have the potential to reduce the time required for FDA review and make a therapy available to patients earlier than would be traditionally possible.

“This Fast Track designation highlights the urgent need for new, innovative ovarian cancer treatments that can maintain patients in remission longer and ultimately increase survival,” said Dr. Marc Mansour, chief executive officer of Immunovaccine.

Immunovaccine has previously reported positive results from DPX-Survivac clinical studies in ovarian cancer patients. In these studies, robust and durable CD8 T cell responses were observed in almost all patients receiving a specified regimen of the vaccine. The vast majority of ovarian cancer patients enrolled in these studies were in remission with no evidence of disease. Notably, a patient with stable but measurable disease achieved a partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). The PR, which persisted following discontinuation of treatment, was accompanied by reduction in levels of a commonly used ovarian cancer biomarker (CA125) and a significant increase in vaccine-induced immune responses. The patient benefited from the DPX-Survivac therapy for more than 8 months demonstrating a potentially durable effect of the therapy.

Immunovaccine is finalizing the design of a large randomized Phase II trial in ovarian cancer to be sponsored and conducted by Canada’s NCIC Clinical Trials Group (NCIC CTG).

The company also recently announced that it has received clearance from Health Canada to conduct a Phase II clinical study of DPX-Survivac in patients with diffuse large B cell lymphoma (DLBCL). The Company-sponsored trial, expected to begin in early 2015, will evaluate DPX-Survivac in combination with oral cyclophosphamide, an immune modulating agent, in patients with recurrent DLBCL. Immunovaccine expects initial data from this study in the second half of 2015. Positive trial results could provide rationale for the initiation of a pivotal trial in recurrent DLBCL which could lead to the approval of DPX-Survivac for the treatment of DLBCL.

Data Investigating KEYTRUDA® (pembrolizumab), Merck’s Anti-PD-1 Therapy, in Patients with Advanced Triple-Negative Breast Cancer Presented at 2014 San Antonio Breast Cancer Symposium

On December 10, 2014 Merck reported early study findings demonstrating an overall response rate of 18.5 percent with KEYTRUDA, the company’s anti-PD-1 therapy, as assessed by RECIST v1.1, central review (n=5/27), in PD-L1 positive, advanced triple-negative breast cancer – one of the most aggressive forms of breast cancer (Press release Merck & Co, DEC 10, 2014, View Source;0 [SID:1234501156]). At the time of analysis, the median duration of response had not been reached with three of five responders on therapy for 11 months or more (range, 15 to 40+ weeks). These early findings, from the ongoing Phase 1b KEYNOTE-012 study, were shared today for the first time as part of the official press program at the 2014 San Antonio Breast Cancer Symposium (SABCS) (ABSTRACT #S1-09) and will be presented in an oral session at 10:45 a.m. CST by Dr. Rita Nanda, the University of Chicago.

“Metastatic, triple-negative breast cancer is an aggressive and often difficult to treat disease,” said Dr. Rita Nanda, associate director, breast medical oncology, the University of Chicago and principal investigator for the KEYTRUDA triple-negative breast cancer Phase 1b study cohort. “The results presented at this year’s SABCS, while early, show encouraging anti-tumor activity in these patients, most of whom had received multiple prior chemotherapies.”

“This year, Merck has significantly advanced our immuno-oncology development program and new data for KEYTRUDA have been presented in seven different cancers, including these first findings in triple-negative breast cancer,” said Dr. Alise Reicin, vice president, global clinical development, oncology, Merck Research Laboratories. “These early data with KEYTRUDA show responses in patients with one of the most aggressive forms of breast cancer and further our understanding of the PD-1 pathway’s role in this disease. Our Phase 2 study planned for the first half of 2015 will be an important next step for our breast cancer clinical program.”

Early Findings Evaluating KEYTRUDA in Advanced Triple-Negative Breast Cancer

Data presented were from a cohort of the ongoing Phase 1b KEYNOTE-012 study which evaluated KEYTRUDA monotherapy at 10 mg/kg every two weeks in patients with advanced TNBC whose tumors were determined to be positive for PD-L1 expression (n=32). As measured by Merck’s proprietary PD-L1 immunohistochemistry (IHC) clinical trial assay, tumors were considered to be PD-L1 positive if staining was present in the stroma or in greater than or equal to one percent of tumor cells. In the study, 58 percent of patients screened had tumors determined to be positive for PD-L1 expression. Most patients enrolled in this study had received two or more prior chemotherapies for metastatic disease and 87.5 percent had received prior neo-adjuvant or adjuvant therapy.

Antitumor Activity with KEYTRUDA by Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1, Central Review*
Patients Evaluable for Response
(n=27)(a)
Overall Response Rate (ORR), n (%) 5 (18.5%)
Best Overall Response, n (%)
Complete Responseb 1 (3.7%)
Partial Responseb 4 (14.8%)
Stable Disease 7 (25.9%)
Progressive Disease 12 (44.4%)
No Assessmentc 3 (11.1%)

*Analysis cut-off as of: November 10, 2014.

a Includes patients with measurable disease at baseline who received ≥1 pembrolizumab dose and who had ≥1 post-baseline scan or discontinued therapy before the first scan due to progressive disease or a treatment-related AE. Five patients were excluded because they did not have any assessments per central review (n=2) or because they did not have measurable disease per central review at baseline (n=3).

b Confirmed responses only.

c “No assessment” signifies patients who discontinued therapy before the first post-baseline scan due to progressive disease or a treatment-related AE.

The median time to response was 18 weeks (range, 7-32 weeks). In the study, 33 percent of patients with KEYTRUDA achieved tumor shrinkage. At six months, the progression-free survival rate with KEYTRUDA was 23.3 percent.

Adverse events were consistent with previously reported safety data for KEYTRUDA. The most common treatment-related adverse events (occurring in greater than or equal to five percent of patients) included arthralgia (n=6), fatigue (n=6), myalgia (n=5), nausea (n=5), ALT increased (n=2), AST increased (n=2), diarrhea (n=2), erythema (n=2) and headache (n=2). Grade 3-5 treatment-related adverse events occurred in a total of five patients and included anemia, disseminated intravascular coagulation (DIC), headache, meningitis aseptic, decreased blood fibrinogen, and pyrexia. Two patients discontinued KEYTRUDA due to adverse events. One treatment-related death was reported in a patient with rapidly progressive disease and was due to DIC with thrombocytopenia and decreased blood fibrinogen.