On June 17, 2016 Cell Medica, a leader in developing, marketing and manufacturing cellular therapeutics for cancer and infections, reported a ground-breaking co-development partnership with Baylor College of Medicine (Baylor) to develop next-generation technologies for engineering immune cells with enhanced functions for the treatment of solid tumors (Press release, Cell Medica, JUN 17, 2016, View Source [SID:1234513448]). Schedule your 30 min Free 1stOncology Demo! The collaboration provides Cell Medica with an exclusive license over several Baylor cell and gene technologies and an option to license new products introduced into the co-development partnership by Baylor’s leading research teams in the field of genetically engineered immune cells.
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Next generation technology
The collaboration will build on the recent clinical success of advanced chimeric antigen receptors (CARs) to enable human immune cells to recognize and kill cancer cells expressing tumor-associated antigens. The development plan will apply the CAR technology to natural killer T (NKT) cells as a novel immune cell type with biological properties that may be particularly effective for targeting solid tumors. NKT cells are known to infiltrate tissues where solid tumors arise and kill both malignant cells and cancer-enabling cells such as tumor-associated macrophages. The development plan also includes a genetically engineered T cell receptor (TCR) for use in NKT cells and T cells. The next-generation product concepts will combine the targeting aspects of CAR and TCR technologies with functional engineering to enable the modified immune cells to counteract the powerful inhibitory mechanisms that tumor cells deploy to evade the immune response. Cell Medica expects the collaboration to generate a significant number of new products for its cellular immunotherapy pipeline.
Co-development structure
The collaboration will accelerate the pioneering work of Dr. Leonid Metelitsa, Professor of Paediatrics – Oncology, with CAR-modified NKT cells. In published research, Metelitsa and his team have shown the potential therapeutic advantages of functionally enhanced CAR-modified NKT cells in pre-clinical cancer models. Metelitsa’s research team is part of Texas Children’s Cancer Center and the Center for Cell and Gene Therapy (CAGT) at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital. The CAGT has more than 20 years of experience working with genetically modified immune cells for the treatment of cancer and has conducted more than 40 clinical studies investigating cellular immunotherapies for the treatment of cancer.
Within the co-development structure, Baylor will conduct the pre-clinical and Phase I clinical research under the guidance of the Joint Steering Committee including members from both organizations. Cell Medica will work in parallel to support early product development and will use its substantial experience in manufacturing clinical-grade cell therapies since 2008 to establish robust production processes suitable for industrial scale-up. Following completion of successful Phase I studies, the products will transfer to Cell Medica for later-stage clinical development and commercialization.
The co-development funding will be available to research teams at Baylor with respect to new technologies, which may be utilized to create therapeutic products using modified NKT cells and other immune cells or to improve manufacturing systems. Baylor’s Innovation Development Center (IDC), led by Andrew Wooten, helped to structure this unique co-development partnership and will be responsible for Baylor’s alliance management function. As part of these responsibilities, the IDC will identify complementary technologies from ongoing Baylor research programs that may be included within the co-development plan.
Five product programs have been defined for the initial development plan in addition to a general process technology program. The preclinical development work for two of these programs will be executed by Drs. Gianpietro Dotti and Barbara Savoldo at the Lineberger Comprehensive Cancer Center, University of North Carolina. The Joint Steering Committee for the collaboration will review new product opportunities on a regular basis.
The co-development partnership builds upon the ongoing successful collaboration between Baylor and Cell Medica, supported by the Cancer Prevention and Research Institute of Texas (CPRIT), to develop baltaleucel-T for the treatment of a range of cancers associated with the oncogenic Epstein Barr virus.
License, Option and Co-development Arrangements
Cell Medica has entered into a License and Option Agreement for two platform patents related to engineered NKT cells, three target cancer antigens for CAR-modified NKT cells and a T cell receptor (TCR) technology. In addition, Baylor and Cell Medica have signed a co-development agreement under which Cell Medica will fund research aimed at new products as well as concepts/technologies in both oncology and non-oncology applications. Cell Medica will have an exclusive option to license future products within the co-development plan. Cell Medica has paid an up-front fee for the exclusive licensing arrangements and will make additional payments to exercise its exclusive option to license future products. Baylor is eligible to receive further payments related to late-stage clinical, regulatory approval and sales milestones, as well as single digit royalties for the successful development of specific products. As part of the up-front consideration, Baylor will receive Cell Medica Preference Shares, which are convertible into Common Shares. Specific financial terms have not been disclosed.
"We are very pleased to partner with Cell Medica in a collaboration aimed at unlocking the huge potential of cellular immunotherapy for the benefit of cancer patients," said Dr. Adam Kuspa, senior vice president and dean for research at Baylor College of Medicine. "The co-development partnership represents a novel aspect of this collaboration which will fully engage Baylor in the early stage development work, including Phase I studies".
"This collaboration with Baylor College of Medicine will place Cell Medica at the forefront of new product concepts for CAR-modified immune cells," noted Gregg Sando, CEO of Cell Medica. "Baylor’s leading research capability in this field should add significantly to our pipeline of high value products targeting cancer types that do not respond to conventional treatments."
ARIAD Initiates Submission of New Drug Application for Brigatinib to the U.S. Food and Drug Administration Ahead of Plan
On June 17, 2016 ARIAD Pharmaceuticals, Inc.(NASDAQ:ARIA) reported the initiation of a New Drug Application (NDA) submission for its investigational anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the U.S. Food and Drug Administration (FDA) (Press release, Ariad, JUN 17, 2016, View Source [SID:1234513446]). Schedule your 30 min Free 1stOncology Demo! ARIAD is seeking U.S. marketing approval of brigatinib for patients with ALK+ non-small cell lung cancer (NSCLC) who are resistant to crizotinib. Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK+ NSCLC. The Company is seeking accelerated approval for brigatinib from the FDA and plans to request a priority review of the application.
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"We are ahead of our previously announced schedule for initiating the submission of our brigatinib NDA to the FDA and we are grateful to have breakthrough status from the FDA, which provides the opportunity to utilize the rolling submission process," stated Paris Panayiotopoulos, president and chief executive officer of ARIAD. "If approved, we believe that brigatinib will become an important new medicine for ALK+ NSCLC patients who have become resistant or intolerant to prior crizotinib therapy and will offer additional hope to these patients and their families."
ARIAD’s NDA is a rolling submission which will occur in three parts. The initial submission contains all nonclinical portions of the NDA and will be followed by submissions of the chemistry, manufacturing and controls (CMC) and clinical data. The rolling NDA submission is expected to be complete in the third quarter of 2016.
Phase 2 ALTA Results Presented at ASCO (Free ASCO Whitepaper)
Results from the ongoing Phase 2 ALTA trial of brigatinib reported at this year’s annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) earlier this month showed that, in patients on the 180 mg regimen (Arm B, n=110) with a median follow-up of 8.3 months (range 0.1—20.2), 54 percent achieved a confirmed objective response, the trial’s primary endpoint. In this arm, the median progression free survival (PFS) exceeded one year (12.9 months) in this post-crizotinib setting. Additionally, a confirmed intracranial objective response rate (ORR) of 67 percent (12/18) was achieved in patients with measurable brain metastases.
The most common treatment-emergent adverse events (TEAEs; ≥ 25% of all patients, [Arm B/A]), regardless of relationship to treatment, were nausea (40%/33%), diarrhea (38%/19%), cough (34%/18%), and headache (27%/28%). TEAEs, ≥ grade 3, occurring in ≥ 5 percent of all patients (Arm B/A), were increased blood creatine phosphokinase (9%/3%) and hypertension (6%/6%).
About Brigatinib
Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD. It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell cancer (NSCLC) whose disease is resistant to crizotinib. Brigatinib is currently being evaluated in the global Phase 2 ALTA trial that is the basis for its initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy of brigatinib in comparison to crizotinib.
ARIAD Announces Distribution Agreements for Iclusig® in Latin America and the Middle East/North Africa
On June 17, 2016 ARIAD Pharmaceuticals, Inc. (ARIAD; NASDAQ:ARIA) reported that it has completed two distribution agreements for Iclusig (ponatinib) outside of the United States (Press release, Ariad, JUN 17, 2016, View Source [SID:1234513445]). Schedule your 30 min Free 1stOncology Demo! In Latin America, ARIAD and Pint Pharma International S.A., a company focused on innovative treatments for patients in Latin America with cancer, rare diseases, and genetic disorders, have entered into an agreement for Pint Pharma to commercialize Iclusig in Argentina, Brazil, Chile, Colombia and Mexico. ARIAD has also entered into a separate agreement with Biologix FZCo., a leading distributor of specialty pharmaceuticals in the Middle East region, for Biologix to commercialize Iclusig in the Middle East and North Africa (MENA), including in Saudi Arabia, the Gulf Coast Countries, Lebanon, and selected other countries in the region.
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"Our new distribution agreements for Latin America and the Middle East and North Africa markets demonstrate our commitment to bringing Iclusig to patients around the world who are in need of this important medicine for refractory CML and Ph+ ALL, while continuing to focus our commercial resources on the U.S. market," stated Hugh Cole, chief business officer of ARIAD. "We believe that our new partners in these geographies have the local expertise and commitment to successfully commercialize Iclusig in their markets. In addition to providing a significant share of revenues from these regions, the agreements allow future strategic optionality for ARIAD by including provisions for the buy-back of these Iclusig rights by an acquirer of ARIAD in case of a change in control of ARIAD."
Agreement with Pint Pharma
Pint Pharma has received exclusive rights to commercialize Iclusig following regulatory approval in Argentina, Brazil, Chile, Colombia and Mexico (the "Territory"), with the potential of adding other Latin American countries in the future. ARIAD and Pint have agreed to collaborate to submit marketing authorization approvals in the countries in the Territory. In addition, Pint has agreed to sell Iclusig as an investigational product on a named patient basis in certain countries in the territory where permitted prior to regulatory approval.
In exchange for these rights, ARIAD will receive upfront and potential regulatory milestone payments totaling $15 million. ARIAD will also receive more than 50 percent of net product sales in the Territory through a product supply transfer price.
"Over the past few years, we have focused on bringing important oncology and rare disease treatments to Latin American countries," said David Muñoz, chief executive officer of Pint Pharma. "Together with ARIAD, we plan to work to secure regulatory and reimbursement approvals for Iclusig to be available to refractory Philadelphia-positive leukemia patients in need of new treatment options in the Territory."
The terms of the distribution agreement include an option for an acquirer of ARIAD to buy-back the rights to Iclusig in the Territory following three years from the effective date of the distribution agreement by making specified payments.
Agreement with Biologix FZCo.
Biologix has received exclusive rights to commercialize Iclusig in Bahrain, the Kingdom of Saudi Arabia, Kuwait, Oman, Qatar, the United Arab Emirates, Lebanon, and several other countries in the region. In the initial phase of the agreement, Biologix has agreed to sell Iclusig as an investigational product on a named patient basis in certain countries in the territory where permitted prior to regulatory approval, and thereafter to commercialize Iclusig in those countries in which regulatory approval is achieved.
"We have an established oncology and hematology portfolio with extensive experience in the Middle East, Gulf Coast and North Africa," said Selim Ghorayeb, chief executive officer of Biologix. "Looking ahead to our partnership with ARIAD, we are dedicated to bringing that experience to help appropriate patients access Iclusig for resistant forms of CML and Ph+ ALL."
Under the terms of the distribution agreement, ARIAD will receive more than 50 percent of net product sales in the territory through a product supply transfer price. The agreement also includes an option for an acquirer of ARIAD to buy-back the rights to Iclusig in the territory following three years from the effective date of the distribution agreement by making specified payments.
About CML and Ph+ ALL
CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to the more aggressive phases referred to as accelerated phase and blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. The BCR-ABL protein is expressed in both of these diseases.
About Iclusig (ponatinib) tablets
Iclusig is a kinase inhibitor. The primary target for Iclusig is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD’s computational and structure-based drug-design platform specifically to inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.
Iclusig is approved in the U.S., EU, Australia, Switzerland, Israel and Canada.
In the U.S., Iclusig is a kinase inhibitor indicated for the:
Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.
Limitations of use:
Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML
IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY
See full prescribing information for complete boxed warning
Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.
Please see the full U.S. Prescribing Information for Iclusig, including the Boxed Warning, for additional important safety information.
Systematic Review of 58 Publications of Real-World Use of GARDASIL® Presented at EUROGIN Congress
On June 16, 2016 Merck (NYSE:MRK), known as MSD outside of the United States and Canada, reported that in a systematic review conducted of the global impact and effectiveness of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant], substantial reductions were observed in HPV 6/11/16/18-related infection, genital warts, Pap abnormalities and cervical pre-cancers (Press release, Merck & Co, JUN 16, 2016, View Source [SID:1234513487]). This evaluation of 58 effectiveness and impact studies published during the past 10 years examined the use of GARDASIL in routine vaccination programs in Australia, Europe, North America and New Zealand, and will be presented for the first time during an oral session at the European Research Organization on Genital Infection and Neoplasia (EUROGIN) congress in Austria. A paper detailing this review was also published online on June 14 in the journal Clinical Infectious Diseases (CID).
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Following introduction of vaccination programs with GARDASIL, the earliest impact of the vaccine was seen in the reduction of genital warts. Reductions in genital warts were observed in all nine countries included in this review (based on 28 publications), with declines occurring as early as one year after vaccine introduction in Australia and Germany. Reductions in HPV 6/11/16/18 infection, assessed in 14 publications from five countries (Australia, Belgium, Germany, Sweden and the United States), were also observed shortly after vaccination; for example, reductions in HPV 6/11/16/18 infection were seen within four years in several studies from Australia and the United States. Subsequently, as successive birth cohorts began cervical screening, reductions in cervical pre-cancers were observed within 3-5 years of vaccine program implementation in Australia, Canada, Denmark, Sweden and the United States.
GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] is indicated for use in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16 and 18. GARDASIL is also approved for use in males 9 through 26 years of age for the prevention of anal cancer caused by HPV types 16 and 18, for the prevention of anal dysplasias and precancerous lesions caused by HPV types 6, 11, 16 and 18, and for the prevention of genital warts caused by HPV types 6 and 11. GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.
The review identified 58 studies published from January 2007 through February 2016 that met the pre-specified criteria for assessment of the real-world impact of vaccination with GARDASIL on HPV-related disease. These studies were conducted in nine different countries (Australia, Denmark, Sweden, Belgium, Germany, France, United States, Canada and New Zealand) with varying degrees of HPV vaccination coverage, among populations of different ages, and used different study methods and disease endpoints. Studies reporting only on the bivalent HPV vaccine were excluded. GARDASIL was predominantly, but not exclusively, used in all publications reviewed. Short-term endpoints (reduction in HPV infection and genital warts) and medium-term endpoints (reduction in Pap abnormalities and cervical pre-cancers) were assessed. Cervical cancer, however, was not identified because most vaccinated cohorts have not yet reached ages when cervical cancer is typically diagnosed. Thus the anticipated benefit of vaccination on certain HPV-related cancer rates cannot be fully determined yet, because of the long latency periods following exposure to HPV.
In this review of the studies, decreases in the prevalence of HPV 6/11/16/18 infections, genital warts, Pap abnormalities and cervical pre-cancers were observed among females in their teens and 20s subsequent to the introduction of GARDASIL. Decreases were generally highest in younger populations, reflecting a lower likelihood of pre-existing HPV infection at time of vaccination, supporting global recommendations for routine use of HPV vaccine in adolescents.
"Based on this comprehensive review of studies published during the past 10 years since the licensure of GARDASIL, reductions in HPV infections as well as reductions in the prevalence of HPV 6/11/16/18-related diseases, as noted by decreases in Pap abnormalities, cervical pre-cancers, and genital warts, were detected within four years after vaccine introduction," said Professor Suzanne Garland, M.D., director of microbiological research and head of clinical microbiology and infectious diseases, The Royal Women’s Hospital, Victoria, Australia, who will present these data at EUROGIN and is lead author on the CID publication. "Despite the progress we have made with Pap screening and vaccination, cervical cancer and other HPV-related diseases are still a public health issue in both developed and developing nations, which underscores the need for comprehensive HPV vaccination programs in adolescents before they’re at risk of contracting the virus," added Garland.
Results varied depending on the vaccine coverage (percent of the population who had been vaccinated), breadth of the immunization program (the age range of those vaccinated and whether catch-up vaccination was included), the number of doses received, the study design, and the disease outcome assessed. The overall impact on the population was greatest in countries that achieved high vaccination rates soon after the introduction of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] and in the youngest cohorts. For example, in Australia, a country with 3-dose vaccination coverage of 73 percent among adolescent females, prevalent HPV 6/11/16/18-related infection decreased by 86 percent in females 18-24 years of age after three doses within six years of vaccine introduction, compared to unvaccinated women during the same timeframe. Furthermore, a 92.6 percent reduction in genital warts diagnosed among females <21 years of age was observed four years after the vaccine program was initiated. Within four years of vaccine introduction in Australia, reductions in cervical pre-cancers were seen in females 11-27 years old at the start of the vaccination program in 2007 and who received all three vaccine doses, with declines ranging from 57 percent in females 15-18 years old to 5 percent in females 23-27 years old. Reductions in disease endpoints were generally lower in older individuals and in countries with lower vaccine coverage. For example, in the same Australian study where a 92.6 percent reduction in genital warts was observed in females <21 years of age, the reduction in genital warts in females 21-30 years of age was 72.6 percent. Reductions in genital warts were <50 percent in teens 15-19 years old in France and Germany where vaccine coverage was much lower than Australia.
"These data reinforce that GARDASIL is important in the fight against cervical cancer and certain other HPV-related cancers and diseases, however the full public health potential of HPV vaccination of males and females is not yet realized even after a decade of use," said Jacques Cholat, M.D., president of Merck Vaccines. "Increasing HPV vaccination rates and access to the vaccine has the potential to make an even greater impact globally."
Systematic review of 58 peer-reviewed publications
This review synthesized available data assessed through a systematic search of PubMed and Embase for peer-reviewed manuscripts from January 2007 through February 2016. The search identified observational studies that reported on the impact or effectiveness of GARDASIL on HPV infection, genital warts, cervical abnormalities and pre-cancers. Both vaccine effectiveness and impact aim at evaluating ‘real-life benefit’ and are typically measured through observational studies. Vaccine impact denotes the population-prevented fraction of infection or disease and is assessed by comparing prevalence or incidence in the vaccine era to a comparable population from the prevaccine era or by measuring population-level trends over time. Vaccine effectiveness corresponds to the proportion of infection or disease prevented among vaccinated individuals, and is estimated by comparing the incidence in vaccinated versus unvaccinated individuals within similar populations. After screening 903 papers, 58 publications from nine countries met the pre-specified inclusion criteria.
Important information about GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant]
GARDASIL does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Recipients of GARDASIL should not discontinue anal cancer screening if it has been recommended by a health care provider.
GARDASIL has not been demonstrated to provide protection against diseases from vaccine and non-vaccine HPV types to which a person has previously been exposed through sexual activity.
GARDASIL is not intended to be used for treatment of active external genital lesions; cervical, vulvar, vaginal and anal cancers; cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).
GARDASIL has not been demonstrated to protect against diseases due to HPV types not contained in the vaccine.
Not all vulvar, vaginal and anal cancers are caused by HPV, and GARDASIL protects only against those vulvar, vaginal and anal cancers caused by HPV Types 16 and 18.
GARDASIL does not protect against diseases not caused by HPV. Vaccination with GARDASIL may not result in protection in all vaccine recipients.
Select safety information for GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant]
GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.
Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following vaccination with GARDASIL. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.
GARDASIL is not recommended for use in pregnant women.
The most common adverse reaction was headache. Common adverse reactions that were observed among recipients of GARDASIL at a frequency of at least 1.0 percent and greater than placebo were fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus and bruising.
Dosage and administration for GARDASIL
GARDASIL should be administered in 3 separate intramuscular injections in the deltoid region of the upper arm or in the higher anterolateral area of the thigh over a 6-month period with the first dose at an elected date, the second dose 2 months after the first dose, and the third dose 6 months after the first dose.
About GARDASIL
GARDASIL is approved for use in 132 countries. To date, more than 208 million doses have been distributed worldwide.
About HPV and related cancers and diseases
In the United States, human papillomavirus (HPV) will infect most sexually active males and females in their lifetime. According to the CDC, there are approximately 14 million new genital HPV infections in the United States each year, half of which occur in people 15 through 24 years of age. For most people, HPV clears on its own, but for others who don’t clear the virus, it could lead to cancers and other diseases in males as well as females, and there is no way to predict who will clear the virus.
In women, HPV causes virtually all cervical cancer cases of which an estimated 70 percent are caused by HPV types 16 and 18. Each day another 35 women are diagnosed with cervical cancer in the United States — about 12,900 women per year. HPV also causes approximately 70-75 percent of vaginal cancer cases and approximately 30 percent of vulvar cancer cases. HPV types 16 and 18 cause an estimated 65% of hpv-related vaginal cancer cases and 75% of hpv-related vulvar cancer cases. Additionally, there are an estimated 3 million abnormal Pap results, many of which are caused by HPV, that require follow-up each year in the United States.
HPV causes approximately 85-90 percent of anal cancers in both males and females, and HPV types 16 and 18 cause an estimated 85% of those cases. According to the American Cancer Society, an estimated 2,600 men and 4,600 women in the United States will be diagnosed with anal cancer in 2015, and overall rates have been increasing. There is no routine screening recommended for the general population to screen for anal cancer.
HPV causes approximately 90 percent of genital warts in both males and females. There are approximately 360,000 cases of genital warts each year in the United States. Treatment of genital warts can be painful, and they may recur after treatment, especially in the first three months. Approximately 3 out of 4 people get them after having genital contact with someone who has genital warts.
Navidea Announces Presentation of Results Demonstrating Performance of Lymphoseek® in Breast Cancer at SNMMI
On June 16, 2016 Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB), reported results from three investigator-initiated studies that demonstrate beneficial performance characteristics of Lymphoseek (technetium Tc 99m tilmanocept) injection and positive comparative results versus commonly-used, non-receptor-targeted imaging agents (Press release, Navidea Biopharmaceuticals, JUN 16, 2016, View Source;p=irol-newsArticle&ID=2178174 [SID:1234513414]). The data were presented by the investigators this week at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in San Diego, CA.
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"These data further reinforce the beneficial clinical performance attributes of Lymphoseek (technetium Tc 99m tilmanocept) Injection. And, in addition, they support Lymphoseek’s rapid adoption in sentinel lymph node biopsy procedures and its pre-surgical imaging utility for other solid tumors," commented Michael Blue, M.D., Senior Medical Director of Navidea. "We believe results from these and other performance-based studies will encourage surgeon’s to use Lymphoseek as they look to optimize outcome for their patients and improve patient experience."
Experimental Results
In the presentation entitled, "Performance of Tc-99m tilmanocept when used alone is as or more effective in localizing sentinel nodes than sulfur colloid plus blue dye," Jonathan Unkart and Anne Wallace, M.D., Department of Surgery at the University of California San Diego (UCSD), described a retrospective evaluation of the rate of localization of Lymphoseek when used alone compared to sulfur colloid (SC), blue dye (BD) and SC plus BD. The study included results from 148 breast cancer patients evaluated in two, prospective Phase 3 Lymphoseek clinical trials (data published in Annuls of Surgical Oncology 2013). SC and BD data was derived from a literature search presented at SNMMI 2013 Annual Meeting including treatment groups of 17,814 SC alone, 12,821 BD alone and 19,627 SC+BD patients. Results show the following localization rates: Lymphoseek alone: 0.9865, SC alone: 0.9249, BD alone: 0.8294 and SC+BD: 0.9636. The author’s analysis suggests that Lymphoseek provided superior sentinel lymph node localization in breast cancer patients compared to the other non-targeting agents alone or in combination providing surgeons the option to use just a single agent.
The presentation, "Use of lymphoscintigraphy with Tc-99m tilmanocept does not affect the number of nodes removed during sentinel node biopsy (SLNB) in breast cancer," also presented by Dr. Unkart shows data from a retrospective review evaluating whether there is a difference in the number of nodes removed using Lymphoseek during SLNB in patients who had a pre-operative imaging procedure called lymphoscintigraphy prior to SLNB versus those who only had intra-operative Sentinel Node (SN) identification. The results indicate that in Breast Cancer, identification and removal of SNs using lymphoscintigraphy (3.0 SNs) did not significantly alter the number of SLNs removed during a SLNB procedure with no imaging (2.7 SNs). Lymphoseek’s selective-targeting performance characteristic enables the utilization of only a single dose of Lymphoseek per patient irrespective of whether both lymphoscintigraphy and SLNB are performed. The authors concluded that by using Lymphoseek, lymphoscintigraphy imaging procedures may be eliminated in this patient population and may reduce health care cost without impacting patient outcomes.
The presentation entitled, "Rate of sentinel lymph node visualization in fatty breasts: Tc-99m Tilmanocept versus Tc-99m filtered sulfur colloid," describes results from a study at Emory University School of Medicine using Lymphoseek in patients with fatty breast tissue a population that is known to be more difficult to localize nodes when doing SLNB. The results suggest that Lymphoseek more effectively visualized sentinel lymph nodes (SLN) both on lymphoscintigraphy and during surgery compared to filtered sulfur colloids (Tc-SC) with 100% localization using Lymphoseek intraoperatively. Dr. Maryam Shahrzad, M.D. presented retrospective data compiled from 29 consecutive patients with early stage breast cancer where lymphoscintigraphy was performed using Tc-SC and 28 patients where lymphoscintigraphy was performed using Lymphoseek. Multiple patient variables were recorded. The Tc-SC cohort included 96% of patients with fatty breasts versus 89% in the Lymphoseek group. Statistically significant findings included:
In lymphoscintigraphy, SLN visualization occurred in 86% of the Lymphoseek group compared to 59% of the TC-SC group. (p-value: 0.02)
At surgery, 100% of patients in the Lymphoseek group showed a "hot" SLN compared to only 79% of patients in the Tc-SC group. (p-value: 0.01)
About Lymphoseek
Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumor, which have the highest probability of harboring cancer. Lymphoseek is approved by the U.S. Food and Drug Administration (FDA) for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.
Accurate diagnostic evaluation of cancer is critical, as results guide therapy decisions and determine patient prognosis and risk of recurrence. Overall in the U.S., solid tumor cancers may represent up to 1.2 million cases per year. The sentinel node label in the U.S. and Europe may address approximately 600,000 new cases of breast cancer, 160,000 new cases of melanoma and 100,000 new cases of head and neck/oral cancer diagnosed annually.
Lymphoseek Indication and Important Safety Information
Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:
Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
Important Safety Information
In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).
Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.
Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers. In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).
FULL LYMPHOSEEK PRESCRIBING INFORMATION CAN BE FOUND AT: WWW.LYMPHOSEEK.COM