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.

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."

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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On December 9, 2014 Ignyta reported that the World Health Organization (WHO) has approved the international nonproprietary name (INN) "entrectinib" for the company’s lead product candidate, RXDX-101 (Press release Ignyta, DEC 9, 2014, View Source [SID:1234501138]). INNs facilitate the identification of active pharmaceutical ingredients, and each INN is a globally recognized unique name.

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About Entrectinib (formerly RXDX-101)

As a novel, orally available, selective tyrosine kinase inhibitor of the Trk family of tyrosine kinase receptors (TrkA, TrkB and TrkC), ROS1 and ALK proteins, entrectinib is designed as a targeted therapeutic candidate to treat patients with cancers that harbor activating alterations to TrkA, TrkB, TrkC, ROS1 or ALK. Entrectinib has demonstrated in vivo antitumor activity against various TrkA, ROS1 or ALK-driven mouse xenograft models of different human cancers, and has demonstrated oral bioavailability and been observed to efficiently cross the blood brain barrier in three animal species.

Entrectinib is currently in two Phase I/II clinical trials, the STARTRK-1 trial and the ALKA-372-001 trial. The company presented interim results from the ALKA-372-001 study in September 2014 at the ESMO (Free ESMO Whitepaper) annual meeting. The interim findings at such date showed:

No dose-limiting toxicities were observed, and only one Grade 3 or higher possibly drug-related adverse event was observed (Grade 3 fatigue, which subsided with dose reduction);
Eight patients remained on active treatment across the three dosing schedules, with four patients having received 9 to 21 cycles of treatment;
Entrectinib demonstrated a complete response in a patient with ROS1-positive non-small cell lung cancer (NSCLC);
Entrectinib demonstrated five partial responses, in patients with three different cancer histologies (colorectal cancer, NSCLC and neuroblastoma) and in patients with each of TrkA, ROS1 and ALK alterations; and
Entrectinib demonstrated prolonged stable disease in two patients: one with ALK-positive NSCLC and one with ROS1-positive pancreatic cancer.

On December 8, 2014 iTeos Therapeutics SA reported a strategic collaboration with Pfizer Inc. pursuant to which iTeos will license to Pfizer rights to iTeos’ pre-clinical compounds targeting Indoleamine 2,3-dioxygenase (IDO1) and Tryptophan 2,3-dioxygenase (TDO2) (Press release, iTeos Therapeutics, DEC 8, 2014, View Source [SID:1234512318]). Pfizer will be responsible for the development and commercialization of IDO1 and TDO2 drug candidates. Additionally, the parties will collaborate to discover and validate new targets that play key roles in the ability of tumors to evade immune responses. These new targets will be shared by iTeos and Pfizer for further independent or collaborative development.

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"This strategic collaboration is a transformative opportunity for iTeos," said Michel Detheux, Ph.D., chief executive officer of iTeos. "The oncologic expertise of Pfizer will help enable the acceleration and expansion of the scope of iTeos’ IDO1 and TDO2 programs. Furthermore, by working with Pfizer, we aim to produce a series of new targets that have the potential to be further developed by iTeos or Pfizer. This expansion of our drug discovery programs is expected to provide additional, novel immunomodulators for future treatment of cancer patients. The successful integration of Ludwig Cancer Research science into iTeos’ preclinical discovery platform in just two years following inception of the company made this collaboration possible."

"This collaboration with iTeos is another important step for Pfizer as we continue to build an industry-leading pipeline of cancer immunotherapeutics, a critical facet of which is the promising class of small molecule immunomodulators," said Robert Abraham, Ph.D., Senior Vice President and Chief Scientific Officer, Oncology Research Unit, Pfizer. "With iTeos’ strong expertise and experience in tumor immunology, this collaboration is well-positioned to help us deliver on our commitment to help bring new therapies to patients."

iTeos will receive from Pfizer an up-front payment of € 24 million, plus an equity investment, licensing fees and collaborative funding. Further, iTeos will be eligible to earn potential milestone payments from Pfizer based on the achievement of specific development, regulatory and commercial milestones across the IDO1 and TDO2 programs, in addition to royalties on sales. iTeos also has the opportunity to earn additional milestone and royalty payments for any of the new target programs that are advanced by Pfizer.

About IDO1 and TDO2

Indoleamine 2,3-dioxygenase (IDO1) and Tryptophan 2,3-dioxygenase (TDO2) are enzymes that break down the amino acid tryptophan. They are expressed in many cancers. Their elevated expression in tumors locally degrades tryptophan, blunting tumor surveillance by the immune system and as such preventing tumor rejection. Specific inhibitors for each enzyme might permit the treatment of a wider variety of tumors, which often express only one of the two enzymes. In tumors that express both enzymes, the combined use of IDO1 and TDO2 inhibitors could reveal complementary benefit for personalized cancer therapy.