On June 12, 2020 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported it will orally present the results of two studies at the 25th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (Press release, Takeda, JUN 12, 2020, View Source [SID1234561062]). Presentations are available online starting Friday, June 12, 2020, and include positive results from TOURMALINE-MM4, a Phase 3, randomized clinical trial evaluating the effect of single-agent oral NINLARO (ixazomib) as a first-line maintenance therapy in adult patients diagnosed with multiple myeloma who had not been treated with stem cell transplantation. Takeda is also presenting key insights from the US MM-6 trial, which investigates the effectiveness and safety of an in-class transition to oral NINLARO in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients who have previously received a parenteral bortezomib-based triplet induction therapy.

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"The positive data from the Phase 3 trial evaluating NINLARO as a maintenance therapy in patients not eligible for stem cell transplantation showed significant improvement in progression-free survival"

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The TOURMALINE-MM4 trial achieved its primary endpoint, with treatment with NINLARO resulting in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus placebo in adult patients diagnosed with multiple myeloma not treated with stem cell transplantation (hazard ratio [HR] 0.659; CI: 95; p <0.001). This corresponds to a 34% reduction in risk of progression or death in patients treated with NINLARO. The safety profile of NINLARO was consistent with previously reported results of single-agent NINLARO use and there were no new safety signals identified.

"There is a strong need for additional maintenance treatments for multiple myeloma, where currently approved options are limited," said Meletios Dimopoulos, MD, University of Athens School of Medicine and principal investigator of the TOURMALINE-MM4 trial. "Data from this Phase 3 clinical trial reinforce the role of proteasome inhibition as a maintenance therapy and suggest that longer duration of therapy can improve a response, in addition to extending it. These data could be highly impactful for those who currently have limited options, which is often the case with patients not eligible for a stem cell transplant."

Key findings of the TOURMALINE-MM4 trial, to be presented by Dr. Dimopoulos include:

The trial achieved its primary endpoint, with treatment with NINLARO resulting in a statistically significant and clinically meaningful improvement in PFS in adult patients diagnosed with multiple myeloma not treated with stem cell transplantation (hazard ratio [HR] 0.659; CI: 95; p <0.001). Median PFS for patients in the NINLARO arm was 17.4 months compared to 9.4 months in the placebo arm. This corresponds to a 34.1% reduction in risk of progression or death in patients treated with NINLARO.
The secondary endpoint of overall survival (OS) is not yet mature and follow-up is ongoing.
The benefits of NINLARO maintenance were realized in the context of a well-tolerated safety profile and no adverse impact on patients’ quality of life.
The safety profile of NINLARO is consistent with previously reported results of single-agent NINLARO use and there were no new safety signals identified.
The most common treatment emergent adverse events (TEAEs) (with incidence ≥5% higher with ixazomib) were nausea, vomiting, diarrhea, rash, peripheral neuropathy (PN) and pyrexia.
Grade ≥3 TEAEs were experienced by 36.6% of patients receiving NINLARO versus 23.2% receiving placebo.
The rate of new primary malignancies was 5.2% versus 6.2% in the placebo arm.
Discontinuation of treatment due to TEAEs was low, at 12.9% in the NINLARO arm and 8% in the placebo arm.
The rate of on-study deaths was 2.6% in the NINLARO arm compared to 2.2% in the placebo arm.
Updated data from US MM-6 will also be presented orally at EHA (Free EHA Whitepaper). The trial revealed the in-class transition from treatment with parenteral bortezomib to a NINLARO-based treatment, taken by patients at home, allowed for prolonged proteasome inhibitor administration and resulted in an increase in overall response rate from 62% to 70% and an increase in complete response from 4% to 26%. These data suggest promising efficacy without impacting patients’ quality of life. The safety profile of NINLARO treatment in this setting is favorable with no unexpected safety signals identified in US MM-6.

"The positive data from the Phase 3 trial evaluating NINLARO as a maintenance therapy in patients not eligible for stem cell transplantation showed significant improvement in progression-free survival," said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. "Coupled with the US MM-6 trial results of in-class transition from parenteral to oral proteasome inhibitor, these data add to the body of evidence supporting NINLARO could be an effective, tolerable and convenient medicine for patients with multiple myeloma that allows for an increased duration of treatment with proteasome inhibitors resulting in better outcomes."

NINLARO is currently approved in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed / refractory multiple myeloma in more than 65 countries.

About the TOURMALINE-MM4 Trial

TOURMALINE-MM4 is a randomized, placebo-controlled, double-blind Phase 3 study of 706 patients, designed to determine the effect of single-agent oral NINLARO (ixazomib) maintenance therapy on progression-free survival (PFS), compared to placebo, in adult patients newly diagnosed with multiple myeloma not treated with stem cell transplant, who have completed 6-12 months of initial therapy and achieved a partial response or better. For additional information, please visit View Source

About the US MM-6 Trial

US MM-6 is an ongoing open-label, single-arm, multicenter study evaluating the effectiveness and safety of an in-class transition to NINLARO (ixazomib) in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma who received bortezomib-based triplet induction. The primary endpoint is progression-free survival (PFS). Key secondary endpoints include duration of therapy and duration of response. For additional information: View Source

About Multiple Myeloma

Multiple myeloma is a life-threatening rare blood cancer that arises from the plasma cells, a type of white blood cell that is made in the bone marrow. These plasma cells become abnormal, multiply and release a type of antibody known as a paraprotein, which causes symptoms of the disease, including bone pain, frequent or recurring infections and fatigue, a symptom of anemia. These malignant plasma cells have the potential to affect many bones in the body and can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count. The typical multiple myeloma disease course includes periods of symptomatic myeloma followed by periods of remission. Nearly 230,000 people around the world live with multiple myeloma, with approximately 114,000 new cases diagnosed globally each year.

About NINLARO (ixazomib) capsules

NINLARO (ixazomib) is an oral proteasome inhibitor which is being studied across the continuum of multiple myeloma treatment settings. NINLARO was first approved by the U.S. Food and Drug Administration (FDA) in November 2015 and is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. NINLARO is currently approved in more than 65 countries, including the United States, Japan and in the European Union, with more than 10 regulatory filings currently under review. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval.

NINLARO (ixazomib): GLOBAL IMPORTANT SAFETY INFORMATION

SPECIAL WARNINGS AND PRECAUTIONS

Thrombocytopenia has been reported with NINLARO (28% vs. 14% in the NINLARO and placebo regimens, respectively) with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and placebo regimens respectively, such as diarrhea (42% vs. 36%), constipation (34% vs. 25%), nausea (26% vs. 21%), and vomiting (22% vs. 11%), occasionally requiring use of antiemetic and anti-diarrheal medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28% vs. 21% in the NINLARO and placebo regimens, respectively). The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.

Peripheral edema was reported with NINLARO (25% vs. 18% in the NINLARO and placebo regimens, respectively). Evaluate patients for underlying causes and provide supportive care, as necessary. Adjust the dose of dexamethasone per its prescribing information or the dose of NINLARO for severe symptoms

Cutaneous reactions occurred in 19% of patients in the NINLARO regimen compared to 11% of patients in the placebo regimen. The most common type of rash reported in both regimens was maculo-papular and macular rash. Manage rash with supportive care, dose modification or discontinuation.

Thrombotic microangiopathy, sometimes fatal, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in patients who received NINLARO. Monitor for signs and symptoms of TPP/HUS and stop NINLARO if diagnosis is suspected. If the diagnosis of TPP/HUS is excluded, consider restarting NINLARO. The safety of reinitiating NINLARO therapy in patients previously experiencing TPP/HUS is not known.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury, hepatic steatosis, and hepatitis cholestatic have been uncommonly reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and female patients of reproductive potential to use contraceptive measures during treatment and for an additional 90 days after the final dose of NINLARO. Women of childbearing potential should avoid becoming pregnant while taking NINLARO due to potential hazard to the fetus. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation- It is not known whether NINLARO or its metabolites are excreted in human milk. There could be potential adverse events in nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONS

Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease (ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can be administered without regard to the timing of dialysis.

DRUG INTERACTIONS

Co-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONS

The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the NINLARO regimen.

For European Union Summary of Product Characteristics: View Source
For US Prescribing Information: View Source
For Canada Product Monograph: View Source

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

On June 12, 2020 ADC Therapeutics SA (NYSE:ADCT), a clinical-stage oncology-focused biotechnology company leading the development and commercialization of next-generation antibody drug conjugates (ADCs) with highly potent and targeted pyrrolobenzodiazepine (PBD) dimer technology, reported maturing data from LOTIS 2, a pivotal Phase 2 clinical trial of loncastuximab tesirine (Lonca, formerly ADCT-402) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including an overall response rate of 48.3%, a complete response rate of 24.1% and manageable toxicity (Press release, ADC Therapeutics, JUN 12, 2020, View Source [SID1234561061]). The Company also announced interim results from LOTIS 3, a Phase 1/2 clinical trial of Lonca combined with ibrutinib, which highlight the potential of Lonca to advance into earlier lines of therapy in combination with other therapies. The data are being presented in an oral presentation and e-Poster at the virtual 25th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA25).

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"Our two presentations at EHA (Free EHA Whitepaper)25 highlight Lonca’s potential as both a single agent and in combination with other therapies for patients with non-Hodgkin lymphoma," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "In LOTIS 2, Lonca demonstrated important anti-tumor activity and durability, as well as manageable toxicities, across a broad population of hard-to- treat, relapsed or refractory DLBCL patients, including patients with poor prognosis, those who never responded to prior therapy and those who received prior stem cell transplant."

"We are pleased to be on track to file a Biologics License Application (BLA) with the U.S. Food and Drug Administration for Lonca for the treatment of relapsed or refractory DLBCL in the second half of 2020," said Chris Martin, Chief Executive Officer of ADC Therapeutics. "If approved, we look forward to launching Lonca in mid-2021. We are also planning to initiate LOTIS 5, a post-marketing confirmatory clinical trial of Lonca in combination with rituximab, which we believe will support a supplemental BLA for Lonca to be used as a second-line therapy for the treatment of relapsed or refractory DLBCL."

Oral Presentation of Initial Results of Lonca Pivotal Phase 2 Clinical Trial (Abstract S233)

LOTIS 2, a Phase 2, multi-center, open-label, single-arm clinical trial, is evaluating the efficacy and safety of Lonca in patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. Patients received 30-minute intravenous infusions of Lonca once every three weeks at a dose of 150 μg/kg for the first two cycles, followed by 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurred first. As of the data cut-off date of April 6, 2020, 145 patients were enrolled and received a mean of 4.3 cycles of Lonca (range: 1-15).

Key data include:

Lonca achieved an overall response rate (ORR) of 48.3% (70/145 patients) and a complete response rate (CRR) of 24.1% (35/145 patients), compared to an ORR of 45.5% (66/145 patients) and CRR of 20.0% (29/145 patients) in the previous data cut (October 14, 2019)
Patients refractory to first-line or last-line prior therapy had ORRs of 37.9% and 36.9%, respectively
The median duration of response has increased to 10.25 months in the more mature data cut, compared to 6.7 months in the previous data cut (October 14, 2019)
Patients had received a median of 3 prior lines of therapy
The toxicity profile was manageable and no new safety concerns were identified
The most common grade ≥3 treatment-emergent adverse events in ≥10% of patients were: neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), GGT increased (16.6%) and anaemia (10.3%)
"Despite recent advances in DLBCL treatment, outcomes for patients with relapsed or refractory disease remain poor," said Carmelo Carlo-Stella, MD, Professor of Hematology, Humanitas University, Section Chief, Lymphoid Malignancies, Humanitas Cancer Center, and an investigator for the trial. "The substantial single-agent anti-tumor activity Lonca has demonstrated in patients with relapsed or refractory DLBCL who failed established therapies underscores the potential of this CD19-targeted, PBD-based ADC to fill a critical unmet need."

e-Poster with Interim Results of Phase 1/2 Clinical Trial of Lonca Combined With Ibrutinib (Abstract EP1284)

LOTIS 3, a Phase 1/2 open-label, single-arm dose escalation and dose expansion clinical trial, is evaluating the safety and efficacy of Lonca in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL). Lonca is administered as 30-minute intravenous infusions using a standard 3+3 dose escalation design at doses of 60 or 90 μg/kg. Patients receive Lonca every three weeks for the first two doses, with concurrent fixed-dose ibrutinib (560 mg/day, oral) for up to one year. As of the data cut-off date of April 6, 2020, 25 patients have been enrolled, including 23 patients with DLBCL and two patients with MCL, and 18 patients were evaluable for antitumor activity. The trial continues to enroll patients.

Key interim data from the Phase 1 portion of the trial include:

Across both Lonca dose levels of 60 and 90 μg/kg, the combination with ibrutinib has demonstrated an ORR of 66.7% and a CRR of 50.0%
At the recommended Phase 2 Lonca dose of 60 μg/kg, the combination with ibrutinib has demonstrated an ORR of 75.0% and CRR of 58.3%
The combination has a manageable toxicity profile
The most common grade ≥3 treatment-emergent adverse events in ≥10% of patients were thrombocytopenia (20%) and anemia (12%)
Patients had received a median of 2 prior lines of therapy
Pharmacokinetic profiles demonstrate good exposure throughout the dosing interval
"As patients with relapsed or refractory DLBCL or MCL have a poor prognosis and limited salvage treatment options, it is important to explore the potential for combinations of drugs with different mechanisms of action to increase clinical activity compared to either agent alone," said Julien Depaus, MD, Department of Hematology, CHU UCL Namur. "Based on synergies demonstrated in preclinical research and the interim results of the Phase 1 portion of this clinical trial, I believe the combination of Lonca and ibrutinib warrants further evaluation as a treatment option for patients with relapsed or refractory DLBCL or MCL."

Conference Call and Webcast

ADC Therapeutics will host a live conference call and webcast today, Friday, June 12, 2020, at 8:30 a.m. EDT, to highlight the data presented at EHA (Free EHA Whitepaper)25. To access the call, please dial 833-526-8381 (domestic) or +41 225 805 976 (international) and request to join the ADC Therapeutics conference call. A live webcast of the presentation will be available on the Investors section of the ADC Therapeutics website at www.adctherapeutics.com.

About Loncastuximab Tesirine (Lonca)

Loncastuximab tesirine (Lonca, formerly ADCT-402) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, Lonca is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies.

Lonca is being evaluated in LOTIS 2, a pivotal Phase 2 clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and LOTIS 3, a Phase 1/2 trial in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL).

On June 12, 2020 ALX Oncology Holdings Inc., a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported preliminary results from the fully enrolled ALX148 plus rituximab combination cohort of the Phase 1 clinical program at the 25th Annual Congress of EHA (Free EHA Whitepaper) [abstract #EP1247] (Press release, ALX Oncology, JUN 12, 2020, View Source [SID1234561060]). As of April 1, 2020, 33 patients with relapsed or refractory non-Hodgkin Lymphoma (NHL) were administered ALX148 at 10 or 15 mg/kg once per week (QW) in combination with a standard rituximab regimen. The following key results were observed in response-evaluable subjects:

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ALX148 in combination with a standard regimen of rituximab is well tolerated with no maximum tolerated dose reached. The maximum administered dose is 15 mg/kg QW (molar equivalent to 30 mg/kg QW an antibody) with no exposure-dependent cytopenia observed across the exposure range evaluated.
ALX148 10mg/kg plus rituximab (n=22): In all subjects, an overall objective response rate (ORR) of 40.9% and median progression-free survival (mPFS) of 7.4 months were observed.
In patients with aggressive NHL (n=15) an ORR of 33.3% and median duration of response (mDOR) of 5.6 months were observed.
In patients with indolent NHL (n=7) an ORR of 57.1% was observed and mDOR was not reached.
Three patients achieved complete response.
ALX148 15mg/kg plus rituximab (n=11): In all subjects, an ORR of 54.6% was observed and mPFS was not reached.
In patients with aggressive NHL (n=7) an ORR of 42.9% was observed and mDOR was not reached.
In patients with indolent NHL (n=4) an ORR of 75% was observed and mDOR was not reached.
Two patients achieved complete response.
ALX148 demonstrates linear pharmacokinetics at 10 mg/kg and 15 mg/kg QW with near complete peripheral CD47 target occupancy in combination with rituximab at both dose levels.
"With no exposure-dependent cytopenias observed, and a greater response rate observed in the higher dosing cohort of heavily pre-treated subjects with NHL, we believe this study provides compelling evidence for the potential of ALX148 in treating hematologic malignancies," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "The higher ALX148 exposure levels observed in subjects with objective responses is encouraging evidence for the pharmacologic activity of ALX148 and supports higher dose administration in future trials for patients with cancer."

On June 12, 2020 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved an expanded indication for GARDASIL 9 for the prevention of oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58 (Press release, Merck & Co, JUN 12, 2020, View Source [SID1234561059]). The oropharyngeal and head and neck cancer indication is approved under accelerated approval based on effectiveness in preventing HPV-related anogenital disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The trial is currently underway.

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"At Merck, working to help prevent certain HPV-related cancers has been a priority for more than two decades," said Dr. Alain Luxembourg, director, clinical research, Merck Research Laboratories. "Today’s approval for the prevention of HPV-related oropharyngeal and other head and neck cancers represents an important step in Merck’s mission to help reduce the number of men and women affected by certain HPV-related cancers."

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of age for the prevention of cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; cervical, vulvar, vaginal, and anal 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 indicated in males 9 through 45 years of age for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; anal 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.

GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) 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].

Both men and women can be at risk for HPV-attributable oropharyngeal cancer; however, this cancer affects men five times more than women.1 For most people, HPV clears on its own. But, for those who don’t clear the virus, it can cause certain cancers. Oropharyngeal cancer can arise as a result of HPV infection in the oropharynx, which includes the soft palate, side and back wall of the throat, tonsils, and back one-third of the tongue. According to a recent model published by the U.S. Centers for Disease Control and Prevention (CDC), HPV-attributable oropharyngeal cancer has surpassed cervical cancer as the most prevalent type of HPV-related cancer in the U.S.1

1 The CDC analyzed data from the U.S. Cancer Statistics (USCS) to assess the incidence of HPV-associated cancers and to estimate the annual number of cancers caused by HPV, overall and by state, during 2012 to 2016.

The estimated number of HPV-attributable cancers was calculated by multiplying the average number of HPV-associated cancers by the percentage of HPV-attributable cancers diagnosed from 1993 to 2005, before HPV vaccination was available in the U.S.

The detection of HPV DNA in an HPV study is not enough to determine that HPV caused the cancer.

Not all cervical and oropharyngeal cancers are caused by HPV.

Important Information About GARDASIL 9

GARDASIL 9 does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers as recommended by a healthcare provider.

GARDASIL 9 has not been demonstrated to provide protection against diseases caused by:

HPV types not covered by the vaccine
HPV types to which a person has previously been exposed through sexual activity
Not all vulvar, vaginal, anal, oropharyngeal and other head and neck cancers are caused by HPV, and GARDASIL 9 protects only against those vulvar, vaginal, anal, oropharyngeal and other head and neck cancers caused by HPV Types 16, 18, 31, 33, 45, 52, and 58.

GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

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 [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant].

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 of GARDASIL 9 has not been established.

Dosage and Administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid or 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 45 years of age, GARDASIL 9 is administered using a 3-dose schedule at 0, 2 months, and 6 months.
About HPV and HPV-related Cancers and Diseases

According to the CDC, an estimated 14 million new HPV infections occur every year in the United States. HPV is so common that 80% of people who are sexually active get HPV at some point in their life. For most people, HPV clears on its own; but for those who don’t clear the virus, it could cause certain cancers and diseases. There is no way to know which people who have HPV will develop cancer or other health problems. GARDASIL9 (Human Papillomavirus 9-valent Vaccine, Recombinant) helps protect against seven HPV types that cause the majority of HPV-related cancers in the United States. Persistent HPV infection can also lead to pre-cancerous lesions that may require additional follow-up procedures. With the exception of cervical cancer, there is no routinely recommended screening for the detection of HPV-related cancers.

On June 12, 2020 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that it prepaid in full its outstanding term loans on June 12, 2020 (Press release, Sorrento Therapeutics, JUN 12, 2020, View Source [SID1234561058]).

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The prepaid debt, comprised of an initial $100 million term loan and an additional $20 million term loan from certain funds affiliated with Oaktree Capital Management, L.P., was obtained pursuant to a Term Loan Agreement entered into in November 2018.