On October 10, 2017 Acorda Therapeutics, Inc. (Nasdaq:ACOR) reported that it will host a conference call and webcast to report its third quarter 2017 financial results and pipeline updates on Tuesday, October 31 at 8:30 a.m. ET (Press release, Acorda Therapeutics, OCT 10, 2017, View Source [SID1234520911]).

To participate in the conference call, please dial (844) 579-6824 (domestic) or (763) 488-9145 (international) and reference the access code 95686626. The presentation will be available on the Investors section of www.acorda.com.

A replay of the call will be available from 11:30 a.m. ET on October 31, 2017 until 2:59 p.m. ET on November 30, 2017. To access the replay, please dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and reference the access code 95686626. The archived webcast will be available in the Investor Relations section of the Acorda website at www.acorda.com.

On October 10 Merck (NYSE:MRK), known as MSD outside of the United States and Canada, reported results from final analyses of the pivotal Phase III efficacy, immunogenicity, and safety clinical trial for GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) (Press release, Merck & Co, OCT 10, 2017, View Source [SID1234520841]). The data, which showed sustained efficacy for up to six years in the per protocol population, were presented during an oral session at the European Research Organization on Genital Infection and Neoplasia (EUROGIN) congress in Amsterdam, Netherlands.

GARDASIL 9 is a vaccine indicated for use in girls and women 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58; pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11. GARDASIL 9 is also indicated for use in boys and men 9 through 26 years of age for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11. GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL [Human Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine, Recombinant].

These final analyses evaluated study outcomes, including efficacy for up to six years following receipt of first vaccine dose, and antibody responses over five years. Vaccination impact on cervical cytology abnormalities and related therapeutic procedures were also reported. These final analyses are from the base study; a study extension is ongoing to evaluate long term follow-up for an additional 10 years following the end of the base study.

In these analyses at six years, efficacy for GARDASIL 9 against HPV31/33/45/52/58-related cervical pre-cancers (cervical intraepithelial neoplasia Grade 3 (CIN 3) was 100 percent (95% CI: 39·4, 100) in the per-protocol population. Efficacy against HPV type 31/33/45/52/58-related cervical, vulvar, and vaginal disease, persistent infection, cervical cytological abnormalities; cervical biopsy; and cervical definitive therapy ranged from 90-98 percent. Incidence of HPV6/11/16/18-related persistent infection, disease, cytological abnormalities, and procedures was similar in recipients of GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) and GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant].

GARDASIL 9 produced similar antibody protection against the four HPV types in GARDASIL. Antibodies to the HPV types targeted by GARDASIL 9 persisted through five years following vaccination. Geometric mean titer ratios (GARDASIL 9/GARDASIL) for HPV6/11/16/18 varied minimally over time. The two vaccines had similar adverse event profiles; injection-site adverse events were more common with GARDASIL 9; most were mild-to-moderate in intensity. A paper detailing these results was also published online on September 5 in The Lancet.

“These new analyses show that efficacy of GARDASIL 9 in preventing certain HPV-related cancers and diseases was sustained for up to six years,” said Elmar A. Joura, M.D., Associate Professor of Gynecology and Obstetrics at the Medical University of Vienna, General Hospital (AKH), and Comprehensive Cancer Center Vienna, Austria, who presented these data at EUROGIN. “Despite the progress we’ve made with HPV vaccination over the past 11 years, HPV-related cancers and diseases are still a significant public health issue and continued efforts are needed to increase uptake of the vaccine.”

About the study

The clinical trial program for GARDASIL 9 was designed to build upon the efficacy established in clinical trials with GARDASIL. In this Phase III active comparator-controlled, double-blind, randomized clinical trial (Protocol 001), 14,215 females 16-26 years of age were randomized to receive a three-dose series of GARDASIL 9 (n=7,106) or GARDASIL (n=7,109). The primary comparison between GARDASIL 9 and GARDASIL was clinical efficacy for the five additional HPV types. Efficacy of GARDASIL 9 against persistent infection and disease related to the original four HPV types (6, 11, 16, or 18) was inferred based on immunogenicity comparisons. The primary efficacy analysis was conducted in those who received all three doses of vaccine within one year of enrollment, did not have deviations from the study protocol that could affect the evaluation of vaccine efficacy, were negative (PCR negative and seronegative) to the relevant HPV type(s) prior to dose 1, and who remained PCR negative to the relevant HPV type(s) through Month 7 (per-protocol efficacy, or PPE, population).

The primary efficacy evaluation was based on a composite clinical endpoint of HPV 31-, 33-, 45-, 52-, and 58-related cervical, vulvar, and vaginal cancer, and high-grade cervical/vulvar/vaginal disease [CIN 2/3 (cervical intraepithelial neoplasia 2/3) or AIS (adenocarcinoma in situ), VIN 2/3 (vulvar intraepithelial neoplasia 2/3), and VaIN 2/3 (vaginal intraepithelial neoplasia 2/3)]. Additional secondary endpoints related to HPV 31, 33, 45, 52, and 58 were also evaluated. Efficacy for all endpoints was measured starting after the Month 7 visit.

Efficacy of GARDASIL 9 against persistent infection and disease related to HPV types 6, 11, 16, or 18 was inferred from non-inferiority comparisons of geometric mean titers (GMTs) in 16- through 26-year-old girls and women following vaccination with GARDASIL 9 with those following vaccination with GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]. Antibody responses for HPV 6, 11, 16, and 18 (measured by GMTs and seroconversion rates at Month 7) for GARDASIL 9 among young women 16 to 26 years of age were non-inferior to those who received GARDASIL.

Important Information about GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 does not eliminate the necessity for women to continue to undergo recommended cervical cancer screening. Recipients of GARDASIL 9 should not discontinue anal cancer screening if it has been recommended by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against diseases from vaccine HPV types to which a person has previously been exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical, vulvar, vaginal, and anal cancers; or CIN; VIN; VaIN; or AIN.

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers caused by HPV 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL 9

GARDASIL 9 is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or 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 HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in pregnant women.

The most common (≥10%) local and systemic adverse reactions in females were injection-site pain, swelling, erythema, and headache. The most common (≥10%) local and systemic reactions in males were injection-site pain, swelling, and erythema.

The duration of immunity with GARDASIL 9 has not been established.

About GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant)

GARDASIL 9 includes the greatest number of HPV types in any available HPV vaccine. After HPV types 16 and 18, the five additional HPV types in GARDASIL 9 are the most common cervical cancer-causing types worldwide. Seven HPV types in GARDASIL 9 (HPV 16, 18, 31, 33, 45, 52 and 58) cause approximately 90 percent of cervical cancer cases and approximately 80 percent of high-grade cervical lesions (cervical precancers, defined as CIN 2, CIN 3 and AIS) worldwide. These seven HPV types also cause 85-90 percent of HPV-related vulvar cancers, 80-85 percent of HPV-related vaginal cancers, and 90-95 percent of HPV-related anal cancers. HPV types 6 and 11 cause approximately 90 percent of genital warts cases. In addition, approximately 50 percent of cases of low-grade cervical lesions (CIN 1) are caused by the nine HPV types included in the vaccine.

GARDASIL 9 is approved for use in more than 60 countries, and since 2015 more than 26 million doses have been distributed worldwide, although the exact number of doses that have been administered is unknown. GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] is no longer available in the United States.

Dosage and administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh.

For individuals 9 through 14 years of age, GARDASIL 9 can be administered using a
2-dose or 3-dose schedule. For the 2-dose schedule, the second dose should be administered 6-12 months after the first dose. If the second dose is administered less than 5 months after the first dose, a third dose should be given at least 4 months after the second dose. For the 3-dose schedule, GARDASIL 9 should be administered at 0, 2 months, and 6 months.
For individuals 15 through 26 years of age, GARDASIL 9 is administered using a
3-dose schedule at 0, 2 months, and 6 months.
20-year commitment to HPV vaccine research

Prof. Anna Giuliano of Moffitt Cancer Center in Tampa, Fla. presented a review of Merck’s 20-year history of HPV vaccine research during an oral session at EUROGIN. Merck’s proof-of-principle studies with monovalent HPV vaccines in 1997 were followed in 2000 with the start of clinical studies for the quadrivalent HPV vaccine, GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]. First regulatory approvals of GARDASIL were received in 2006. Studies have continued to evaluate duration of protection as well as safety.

HPV types 16 and 18 cause approximately 70 percent of cervical cancer cases. In 2004, HPV types 31, 33, 45, 52, and 58 were classified as the next most frequent HPV types associated with cervical cancer, causing an additional 20 percent of cases. Merck started a Phase II study in 2005 to evaluate a HPV vaccine candidate that could protect against more HPV types. Ultimately this led to the development of the 9-valent HPV vaccine, GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant), which helps to protect against certain cancers and diseases caused by these five HPV types in addition to the four original HPV types covered by GARDASIL. Phase III clinical studies for GARDASIL 9, which evaluated more than 20,000 individuals who received the vaccine, began in 2007, just one year after GARDASIL was licensed.

“Merck has had a sustained and unwavering commitment to HPV vaccine research for 20 years,” said Eliav Barr, MD, senior vice president, Global Clinical Development – Infectious Disease & Vaccines, Merck Research Laboratories. “With HPV vaccination, screening, treatment, and education, it is our aspiration that one day the number of women and men affected by HPV-related cancers and diseases will be significantly reduced. There is obviously much work ahead of us, but we look forward to continuing our efforts in collaboration with the many stakeholders around the world who share our commitment.”

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 certain cancers and other diseases in males as well as females. There is no way to predict who will or won’t clear the virus.

HPV causes virtually all cervical cancer cases. Each day, about 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 in females, and approximately 85-90 percent of anal cancers and 90 percent of genital warts in both females and males. 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.

Anal cancer and genital warts affect both men and women. According to the American Cancer Society, an estimated 2,920 men and 5,160 women in the United States will be diagnosed with anal cancer in 2016, and overall rates have been increasing. There is no routine screening recommended for the general population to reduce the risk of anal cancer. Approximately 355,000 cases of genital warts occur 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.

October 11, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development of gilteritinib for adult patients with FLT3 mutation-positive (FLT3+) relapsed or refractory acute myeloid leukemia (AML) (Press release, Astellas, OCT 10, 2017, View Source [SID1234520835]). Fast Track designation is designed to facilitate the development, and expedite the FDA review, of drugs to treat serious and life-threatening conditions so that, if approved, the compounds can reach the market expeditiously.

“Mutations of FLT3 in AML are associated with a poor prognosis and we are committed to working with the FDA to meet the requirements of the expedited review process,” said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas. “We are pleased that the FDA has acknowledged the urgent need for new therapies for FLT3+ AML patients, which may allow for an expedited review process for gilteritinib.”

Fast Track designation for gilteritinib may allow for more frequent meetings and correspondence with the FDA, consideration for Priority Review if supported by clinical data, and Rolling Review, which means Astellas can submit completed sections of its New Drug Application (NDA) for review by the FDA rather than waiting until every section of the application is completed before the NDA can be reviewed.

AML is a cancer that impacts the blood and bone marrow and is most commonly experienced in older adults. According to the American Cancer Society, in 2016 there were approximately 21,000 new patients diagnosed with AML in the United States and about 10,000 cases resulted in death.

Gilteritinib is an investigational compound that has demonstrated inhibitory activity against FLT3 internal tandem duplication (ITD) as well as FLT3 tyrosine kinase domain (TKD), two common types of FLT3 mutations that are seen in approximately one-third of patients with AML. Further, gilteritinib has also demonstrated inhibition of AXL, which is reported to be associated with therapeutic resistance.

Astellas is currently investigating gilteritinib in various AML patient populations through four ongoing Phase 3 trials, including the registrational ADMIRAL trial in relapsed/refractory FLT3+ AML.

The safety and efficacy of the agent discussed herein are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. Information about pharmaceutical products (including products currently
in development) which is included in this press release are not intended to constitute an advertisement or medical advice.

About Gilteritinib

Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize gilteritinib. Astellas internally classifies highly prioritized research projects as “Fast Track,” meaning research and development time is minimized through the focused investment of both capabilities and resources. Gilteritinib was designated as our first Fast Track project.

On October 10, 2017 Seattle Genetics, Inc. (NASDAQ: SGEN) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, “Astellas”) reported dosing of the first patient in EV-201, a registrational phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with checkpoint inhibitor (CPI) therapy (Press release, Seattle Genetics, OCT 10, 2017, View Source [SID1234520828]). The EV-201 study will assess the antitumor activity and safety of enfortumab vedotin to support potential registration under the U.S. Food and Drug Administration’s (FDA) accelerated approval regulations.

“Locally advanced or metastatic urothelial cancers are often aggressive and treatment-resistant. Treatment options are limited for those many patients who do not respond to chemotherapy and checkpoint inhibitors, or CPIs. In addition, there are no FDA-approved therapies for patients who progress following CPI treatment,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “Initiation of this pivotal phase 2 trial of enfortumab vedotin is a significant advance toward our goal of providing a new treatment option for locally advanced or metastatic urothelial cancer.”

The primary endpoint of the single-arm, open-label trial is confirmed objective response rate (ORR), per independent review. Secondary endpoints include assessments of overall survival, progression free-survival, safety and tolerability. The study will enroll approximately 120 patients at multiple centers globally, and enfortumab vedotin will be administered three of every four weeks for the duration of treatment.

“The initiation of the EV-201 clinical trial demonstrates our continued commitment to patients living with locally advanced or metastatic urothelial cancer,” said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development at Astellas. “Our decision to move forward with this registrational trial is based on the results of our ongoing Phase 1 study, and we look forward to future clinical development milestones for enfortumab vedotin.”

The companies also plan to initiate a combination trial of enfortumab vedotin with CPI therapy in late 2017.

For more information about the phase 2 pivotal trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Urothelial Cancer

Urothelial cancer is most commonly found in the bladder (90 percent). According to the American Cancer Society, approximately 79,000 people in the U.S. will be diagnosed with bladder cancer during 2017 and almost 17,000 will die from the disease. Outcomes are poor for patients diagnosed with metastatic disease, with a five-year survival rate of five percent.

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary, industry-leading linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys (an affiliate of Astellas), which is expressed on many solid tumors.

Nectin-4 is highly expressed in urothelial cancers, particularly in bladder cancer. Preclinical data demonstrate that enfortumab vedotin binds to Nectin-4 on cancer cells and releases the cell-killing agent into these target cells upon internalization.

On October 10, 2017 OncoSec Medical Incorporated (“OncoSec” or the “Company”) (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported that it has initiated its phase 2b registration directed trial, PISCES/KEYNOTE-695 (Press release, OncoSec Medical, OCT 10, 2017, View Source [SID1234520827]). The PISCES/KEYNOTE-695 study is a global, multicenter phase 2b trial of OncoSec’s investigational therapy, ImmunoPulse IL-12 (intratumoral pIL-12 [tavokinogene telseplasmid or “tavo”] with electroporation), combined with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the US and Canada), in patients with unresectable metastatic melanoma who have progressed or are progressing on an anti-PD-1 therapy.

“Patients with metastatic melanoma who are progressing or have progressed on anti-PD-1 therapy have limited treatment options. We believe the combination of ImmunoPulse IL-12 and pembrolizumab offers a potentially transformative approach for these patients given the absence of approved therapies,” said Punit Dhillon, CEO and President at OncoSec. “The advancement of the PISCES trial marks an important milestone for the Company.”

The phase 2b, Simon 2-stage multicenter study of intratumoral tavo with electroporation in combination with intravenous KEYTRUDA will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).

“ImmunoPulse IL-12 and pembrolizumab are immunotherapies designed to modulate the patient’s own immune response to fight cancer,” said Sharron Gargosky Ph.D., Chief Clinical and Regulatory Officer at OncoSec. “We are pleased with the progress of the ongoing PISCES trial, which has benefitted from our clinical trial collaboration and supply agreement with Merck.”

The collaboration agreement, which was announced in May 2017, is between OncoSec Medical Incorporated and Merck, through a subsidiary. Under the agreement, OncoSec will sponsor and fund the study and Merck will provide KEYTRUDA.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov via NCT03132675.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ImmunoPulse is a registered trademark of OncoSec Medical Incorporated, San Diego, CA, USA.

About Metastatic Melanoma1

Melanoma is a type of skin cancer that begins in skin cells called melanocytes. As the cancer progresses, melanoma becomes more difficult to treat once it spreads beyond the skin, such as the lymphatic system (metastatic disease). Given its occurrence young individuals, the potential years of life lost to melanoma can be higher when compared with other cancers. Although melanoma is a rare form of skin cancer, it accounts for over 75% of skin cancer deaths. The American Cancer Society estimates that approximately 87,000 new melanoma cases and 10,000 deaths from the disease will occur in the United States in 2017. Additionally, the World Health Organization estimates that approximately 132,000 new cases of melanoma are diagnosed around the world every year.

1 American Cancer Society (View Source); World Health Organization (View Source)

About PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study)

PISCES is a global, multicenter phase 2b, open-label trial of intratumoral plasma encoded IL-12 (tavokinogene telseplasmid or “tavo”) delivered by electroporation in combination with intravenous pembrolizumab in patients with stage III/IV melanoma who have progressed or are progressing on either pembrolizumab or nivolumab treatment. The Simon 2-stage study of intratumoral tavo plus electroporation in combination with pembrolizumab will enroll approximately 48 patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. The primary endpoint will be the Best Overall Response Rate (BORR).