FDA Approves Amgen’s PCSK9 Drug Repatha

The U.S. Food and Drug Administration today approved Repatha (evolocumab) injection for some patients who are unable to get their low-density lipoprotein (LDL) cholesterol under control with current treatment options.

Repatha, the second drug approved in a new class of drugs known as PCSK9 inhibitors, is approved for use in addition to diet and maximally-tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease, such as heart attacks or strokes, who require additional lowering of LDL cholesterol.

Familial hypercholesterolemia (encompassing both HeFH and HoFH) is an inherited condition that causes high levels of LDL cholesterol. A high level of LDL cholesterol in the blood is linked to cardiovascular or heart disease. Heart disease is the number one cause of death for Americans, both men and women. According to the Centers for Disease Control and Prevention, about 610,000 people die of heart disease in the United States every year– that equals one in every four deaths.

“Repatha provides another treatment option in this new class of drugs for patients with familial hypercholesterolemia or with known cardiovascular disease who have not been able to lower their LDL cholesterol enough with statins,” said John Jenkins, M.D., director of the Office of New Drugs, Center for Drug Evaluation and Research. “Cardiovascular disease is a serious threat to the health of Americans, and the FDA is committed to facilitating the development and approval of effective and safe drugs to address this important public health problem.”

Repatha is an antibody that targets a specific protein, called PCSK9. PCSK9 reduces the number of receptors on the liver that remove LDL cholesterol from the blood. By blocking PCSK9’s ability to work, more receptors are available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.

The efficacy and safety of Repatha were evaluated in one 52-week placebo-controlled trial and eight 12-week placebo-controlled trials in participants with primary hyperlipidemia, including two that specifically enrolled participants with HeFH and one that enrolled participants with HoFH. In one of the 12-week studies, 329 participants with HeFH, who required additional lowering of LDL cholesterol despite statins with or without other lipid-lowering therapies, were randomized to receive Repatha or placebo for 12 weeks. Participants taking Repatha had an average reduction in LDL cholesterol of approximately 60 percent, compared to placebo.

The most common side effects of Repatha include nasopharyngitis, upper respiratory tract infection, flu, back pain, and reactions such as redness, pain, or bruising where the injection is given. Allergic reactions, such as rash and hives, have been reported with the use of Repatha. Patients should stop using Repatha and get medical help if they experience symptoms of a serious allergic reaction.

Multiple clinical trials have demonstrated that statins lower the risk of having a heart attack or stroke. A trial evaluating the effect of adding Repatha to statins for reducing cardiovascular risk is ongoing.

Repatha is marketed by Amgen Inc., of Thousand Oaks, Calif.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

 

 

Source: US Food and Drug Administration (FDA)

Amgen Files for FDA Approval of its Secondary Hyperparathyroidism Drug

amgenTHOUSAND OAKS, Calif., Aug. 25, 2015 /PRNewswire/ — Amgen (NASDAQ: AMGN) today announced the submission of a New Drug Application (NDA) with the United States Food and Drug Administration (FDA) for etelcalcetide (formerly AMG 416) for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on hemodialysis. If approved, etelcalcetide will be the first calcimimetic agent that can be administered intravenously at the end of the dialysis session.

“Secondary hyperparathyroidism is a serious, progressive disease that can lead to significant clinical consequences and is also associated with a high pill burden for patients,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We look forward to working with regulatory authorities during the review process to bring this important treatment to market, helping to fill an unmet need for the many patients impacted by this disease.”

Etelcalcetide is a novel calcimimetic agent that suppresses the secretion of parathyroid hormone and is in clinical development for the treatment of SHPT in patients with CKD on hemodialysis. Etelcalcetide is administered intravenously three times per week at the end of each dialysis session. It acts by binding to and activating the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in parathyroid hormone (PTH). Sustained elevations in PTH are known to be associated with significant clinical consequences for patients with CKD.

The submission includes data from three Phase 3 studies, all of which met the primary endpoints, including two pooled placebo-controlled trials in more than 1,000 patients and a head-to-head study evaluating etelcalcetide compared with cinacalcet.

About Secondary Hyperparathyroidism
SHPT is a common and serious condition that is often progressive among patients with CKD, and it affects many of the approximately two million people throughout the world who are receiving dialysis, including 450,000 people in the U.S. The disorder develops early in the course of CKD and usually manifests as increased levels of PTH as a result of increased production from the parathyroid glands (four small glands in the neck). Patients with end stage renal disease who require maintenance dialysis often have substantial elevations of PTH that are commonly associated with abnormal calcium and phosphorus levels and an increased risk of significant clinical consequences.

About Etelcalcetide (AMG 416)
Etelcalcetide is a novel calcimimetic agent in clinical development for the treatment of SHPT in CKD patients on hemodialysis that is administered intravenously at the end of the dialysis session. Etelcalcetide binds to and activates the calcium-sensing receptor on the parathyroid gland, thereby decreasing PTH levels.

About Sensipar® (cinacalcet)
Sensipar® (cinacalcet) is the first oral calcimimetic agent approved by the FDA for the treatment of SHPT in adult patients with CKD on dialysis. Sensipar is not indicated for use in adult patients with CKD who are not on dialysis because of an increased risk of hypocalcemia. The therapy is also approved in the U.S. for treatment of hypercalcemia in adult patients with parathyroid carcinoma and hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy. Sensipar binds to the calcium-sensing receptor, resulting in a drop in PTH levels by inhibiting PTH synthesis and secretion. In addition, the reductions in PTH lower serum calcium and phosphorus levels.

Important Safety Information
Sensipar® (cinacalcet) treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range (8.4 mg/dL).

Sensipar® lowers serum calcium; therefore, it is important that patients are carefully monitored for the occurrence of hypocalcemia. Life threatening events and fatal outcomes associated with hypocalcemia have been reported in patients treated with Sensipar®, including pediatric patients. Decreases in serum calcium can prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia secondary to hypocalcemia have been reported in patients treated with Sensipar®.

Significant reductions in calcium may lower the threshold for seizures. Patients, particularly those with a history of seizure disorder, should be carefully monitored for the occurrence of low serum calcium or symptoms of hypocalcemia.

In Sensipar® postmarketing use, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia were reported in patients with impaired cardiac function. The causal relationship to Sensipar® therapy could not be completely excluded and may be mediated by reductions in serum calcium levels.

Adynamic bone disease may develop if intact parathyroid hormone (iPTH) levels are suppressed below 100 pg/mL. Patients with moderate to severe hepatic impairment should be monitored throughout treatment with Sensipar®, as cinacalcet exposure assessed by area under the curve (AUC) was higher than in patients with normal hepatic function. Patients with secondary HPT: Serum calcium and serum phosphorus should be measured within 1 week and PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Sensipar®. Once the maintenance dose has been established, serum calcium and serum phosphorus should be measured approximately monthly, and PTH every 1 to 3 months. Patients with primary HPT or parathyroid carcinoma: Serum calcium should be measured within 1 week after initiation or dose adjustment of Sensipar®. Once maintenance dose levels have been established, serum calcium should be measured every 2 months. In clinical trials of patients with secondary HPT comparing Sensipar® to placebo, the most commonly reported side effects were nausea (31 percent vs. 19 percent), vomiting (27 percent vs. 15 percent), and diarrhea (21 percent vs. 20 percent). In clinical trials of patients with primary HPT and parathyroid carcinoma treated with Sensipar®, the most commonly reported side effects were nausea (63 percent), vomiting (46 percent), and paresthesia (20 percent).

Please see Full Prescribing Information.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

First Patient Enrolled in CSL Behring’s On-Demand Treatment for Patients with Hemophilia A or B with Inhibitors

KING OF PRUSSIA, Pa. — 25 August 2015

  • Key milestone achieved in CSL Behring’s PROLONG-7FP clinical development program
  • PROLONG-7FP is studying CSL Behring’s recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP)
  • Milestone underscores CSL Behring’s focused scientific expertise and deep commitment to developing and delivering innovative specialty biotherapies for people with serious diseases

CSL Behring announced today that the first patient has been enrolled in its Phase II/III clinical study evaluating the pharmacokinetics (PK), efficacy, and safety of the company’s recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP) for on-demand treatment in patients with congenital hemophilia A or B who have developed an inhibitor to factor VIII or factor IX replacement therapy. The study will enroll approximately 54 male patients, the first of whom was enrolled in Malaysia.

“CSL Behring has a thorough understanding of the bleeding disorders community, focused scientific expertise and a strong commitment to developing and delivering innovative specialty biotherapies that treat serious medical conditions,” said Dr. Andrew Cuthbertson, Chief Scientific Officer and Director of R&D, CSL Limited. “Our commitment, expertise and understanding helped CSL to develop rVIIa-FP, based on the innovative recombinant albumin fusion technology platform, to treat patients with hemophilia A or B with inhibitors as well as congenital factor VII deficiency.”

About Hemophilia A or B with Inhibitors

Hemophilia is an inherited bleeding disorder characterized by prolonged or spontaneous bleeding, especially into the muscles and joints. The disorder is caused by deficient or defective blood coagulation proteins known as factor VIII (hemophilia A) or IX (hemophilia B). The recommended treatment for these patients is factor replacement therapy. Development of inhibitory antibodies against factor VIII or factor IX is a major complication associated with replacement therapy and may partially or completely prevent the efficacy of factor replacement therapy. The incidence of inhibitors in individuals with hemophilia A is estimated to be up to 33 percent and between one and 6 percent in patients with hemophilia B. The most recent World Federation of Hemophilia (WFH) survey identified more than 4,753 patients with hemophilia A and 248 with hemophilia B who have developed an inhibitor worldwide.1

About rVIIa-FP

Preclinical studies have confirmed that CSL Behring’s rVIIa-FP (also known as CSL689) has favorable pharmacokinetic properties compared with the existing recombinant FVIIa product.2 In a phase I study in healthy volunteers, rVIIa-FP showed a good tolerance, and a 3- to 4-fold increase in half-life compared with the commercially available rFVIIa-product (median 8.5h).3

The European Commission granted Orphan Drug Designations for rVIIa-FP for the treatment of patients with hemophilia A or B who have developed an inhibitor as well as the treatment of congenital factor VII deficiency. rVIIa-FP also received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia and inhibitors to coagulation factor VIII or IX. Orphan designation qualifies the sponsor of the product for important benefits such as tax credits for qualified clinical testing and exemption from certain application fees.

For more information about CSL Behring’s recombinant products in development to treat hemophilia, visithttp://www.cslbehring.com/products/bleeding-disorders/novel-recombinant-hemophilia-treatments.

About PROLONG-7FP Clinical Development Program

This Phase II/III study in patients with hemophilia A or B who have developed an inhibitor is a part of the PROLONG-7FP clinical development program. This program aims to demonstrate the therapeutic advantages of rVIIa-FP in patients with hemophilia A or hemophilia B who have developed inhibitors as well as in patients with congenital FVII deficiency. A Phase I PK study in patients with congenital FVII deficiency is ongoing.

For more information about the Phase II/III study, please visit clinicaltrials.gov.

About CSL Behring

The people and science of CSL Behring save lives around the world. We develop and deliver innovative specialty biotherapies, driven by our 100-year promise to help people with life-threatening conditions live full lives. With 14,000 employees and operations in 30 countries, CSL applies world-class R&D, high-quality manufacturing and patient-centered management.

CSL Behring therapies are used around the world to treat coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease, and neurological disorders in certain markets. The company’s products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic disease of the newborn.

CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a global biopharmaceutical company and a member of the CSL Group of companies. The parent company, CSL Limited (ASX:CSL), is headquartered in Melbourne, Australia. For more information, visit www.cslbehring.com.

Banner MD Anderson to Test New Drug for Late-Stage Pancreatic Cancer

GILBERT, AZ – A new clinical trial at Banner MD Anderson Cancer Center aims to test a new treatment to fight late-stage pancreatic cancer, one of the nation’s deadliest cancers. About 73 percent of patients with pancreatic cancer die in the first year of diagnosis, according to the American Cancer Society.

The drug known as PEGPH20 is designed to crack the protective shell around the pancreatic tumor, so that the chemotherapy can more effectively reach the cancer cells inside the tumor. The drug, made by Halozyme Therapeutics, contains an enzyme that breaks down a hard tissue component produced by most pancreatic tumors. The removal of this component from tumors in earlier studies has been shown to increase the ability of chemotherapy to penetrate the tumor. In this trial, the drug PEGPH20 is given in combination with chemotherapy drugs.

“We’re excited to be involved in this clinical trial, which takes on a new and unique approach in targeting pancreatic cancer,” said Tom Dragovich, MD, PhD, Division Chief of Medical Oncology and Hematology, who is leading the study at Banner MD Anderson. “There remains a significant need for better treatment options for pancreatic cancer patients, and we need to accelerate investigations of the new and promising therapies for this disease.”

Pancreatic cancer is currently the fourth leading cause of cancer death in the United States, and is anticipated to become second by 2020, according to the American Cancer Society.

Several standard treatment options are available to pancreatic cancer patients. Early detection of pancreatic cancer is difficult and surgical removal is possible in only about 15 percent of patients with ductal adenocarcinoma, the most common type of pancreatic cancer.  For those patients whose tumors cannot be removed surgically, chemotherapy, radiation therapy or investigational therapies are considered. Several new therapies are currently being explored in clinical trials such as this study.

The study is specifically for patients with stage IV metastatic pancreatic cancer. To learn more about the trial, call (480) 256-6444.

Banner MD Anderson, located on the Banner Gateway campus, delivers cancer care to patients in Arizona through the collaboration of Banner Health and MD Anderson Cancer Center. Banner MD Anderson offers focused disease-specific expertise in the medical, radiation, and surgical management of the cancer patient; an evidence-based, multidisciplinary approach to patient care; access to clinical trials and new investigative therapies; state-of-the-art technology for the diagnosis, staging and treatment of all types of cancer; oncology expertise in supportive care services.

Source: Banner Health

Eighty Percent of Physicians Want More Education on Biosimilars

biosimsWALTHAM, Mass.–(BUSINESS WIRE)–Quantia, Inc.—the platform for Physician Engagement—today announced key findings from its new report, “Reading the Signs: A Roadmap for Increasing Physician Engagement in the Biosimilars Market.” The report examines healthcare professionals’ awareness of biosimilar drugs, potential barriers to adoption, and opportunities to provide education that may drive prescribing decisions.

Key findings from this report include:

  • 94% of physician respondents believe biosimilars will provide value to healthcare
    • Top value cited is “lower costs to patients/the health system” (35%), followed by “greater patient access to therapies” (30%) and “increased choice among prescribing options” (27%)
  • Only 17% of prescribing specialists (those who see patients with conditions commonly treated with biologics) report they would be “very likely” to prescribe biosimilars to eligible patients
    • Main concerns include safety/efficacy, drug substitution regulations, and accurate evaluation of when to prescribe a biosimilar vs. branded therapy
  • Specialty societies were prescribing specialists’ most trusted source of information about biosimilars (25%), followed by peers (19%) and key opinion leaders (18%)
    • 80% of prescribing specialists say they would want to learn about biosimilars through expert-led digital content

“The survey findings confirm that many physicians already recognize the potential clinical value and cost savings that biosimilars represent, and many are hopeful that these therapies will soon be viable for their patient populations. The challenge is offering the education and support, through the appropriate channels, that will reach the physicians who need it most and transform this general awareness into action,” said Dan Malloy, Executive Vice President of Quantia. “These findings—combined with our experience engaging physicians in medically relevant content—offer a roadmap that pharmaceutical companies can put into place to quickly and cost-effectively capitalize on this opportunity.”

Download the full report here: http://info.quantia-inc.com/biosimilars.

Methodology

Leveraging its online community QuantiaMD, which includes more than 225,000 U.S. physicians, Quantia surveyed nearly 300 physicians on the topic of biosimilar therapies in March of 2015.

Survey respondents included Primary Care Physicians and Specialists in the therapeutic areas where biosimilars are currently most concentrated– such as endocrinologists, gastroenterologists, hematologists, oncologists, nephrologists, and rheumatologists.

Responses were analyzed across PCPs and prescribing specialists, as well as across organized systems such as Integrated Delivery Networks/Integrated Health Networks, Independent Practice Associations, Physician Hospital Organizations, and independent/private or group practice.

About Quantia, Inc.

Quantia is on a mission to nurture the wisdom of the physician community – and tap into it to deliver better care. Every day, our membership of over 225,000 physicians (about 1 in 3 nationwide) visits the award-winning web and mobile community QuantiaMD to learn from top experts and collaborate on a wide range of topics. Our blend of expert-led content, gamification, and social framework creates an environment physicians want to explore, serving up high quality interactions that inspire change. Health systems and life sciences organizations use this platform to boost engagement among physicians, improving performance and delivering higher quality, more consistent care. Learn more at www.quantia-inc.com.

FDA Expands Approval of Seattle Genetics’ Adcetris

BOTHELL, Wash.–(BUSINESS WIRE)–Aug. 17, 2015– Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that the U.S. Food and Drug Administration (FDA) has approved ADCETRIS (brentuximab vedotin) for the treatment of patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation. The approval is based on a phase 3 clinical trial called AETHERA that was designed to compare up to 16 cycles (approximately one year) of ADCETRIS therapy administered every three weeks following auto-HSCT to placebo. The primary endpoint was met with a significant improvement in median progression-free survival (PFS) of 42.9 months (95% CI: 30.4, 42.9) for patients who received ADCETRIS versus 24.1 months (95% CI: 11.5, not estimable) for patients who received placebo, an improvement of 18.8 months (hazard ratio=0.57 [95% CI: 0.40, 0.81]; p-value=0.001). In addition, data from the AETHERA trial converted the U.S. accelerated approval of the relapsed classical HL indication to regular approval. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL), as well as other lymphoma subtypes. This is the third indication for ADCETRIS, which was granted accelerated FDA approval in August 2011 for two other indications: (1) treatment of Hodgkin lymphoma patients who fail autologous transplant or who fail at least two prior multi-agent chemotherapy regimens and are not autologous transplant candidates, and (2) treatment of systemic ALCL patients who fail at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Globally, there are more than 65,000 cases of HL diagnosed each year. Although frontline combination chemotherapy can result in durable responses, up to 30 percent of these patients fail frontline treatment. The standard for these patients is salvage therapy, followed by auto-HSCT; approximately half of all HL patients who undergo an auto-HSCT experience subsequent disease relapse.

“With this FDA approval, ADCETRIS is the first and only consolidation treatment option available to high risk classical Hodgkin lymphoma patients who undergo a transplant to preserve their post-auto-HSCT remissions,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “This represents a meaningful advance for cancer patients and an important milestone for the ADCETRIS development program. Together with our three ongoing phase 3 trials and more than 30 additional clinical trials, this approval supports our goal to broadly establish ADCETRIS as the foundation of therapy for classical Hodgkin lymphoma and CD30-expressing malignancies.”

“The FDA approval of brentuximab vedotin for post-autologous hematopoietic transplantation consolidation treatment in classical Hodgkin lymphoma patients with high risk of relapse or progression is a significant milestone for patients and physicians,” said Craig Moskowitz, M.D., lead investigator on the trial and Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center. “Approximately half of all Hodgkin lymphoma patients who undergo an autologous hematopoietic stem cell transplant will relapse, representing a significant need for additional treatment options to improve progression free survival.”

AETHERA Phase 3 Trial Demonstrates Significant Progression-Free Survival Benefit with ADCETRIS as Post-Transplant Consolidation in Hodgkin Lymphoma

The positive results from the phase 3 AETHERA trial were published in The Lancet in March 2015 and presented at the 56th American Society of Hematology (ASH) Annual Meeting in December 2014. A total of 329 HL patients at risk of relapse or progression were enrolled, including 165 on the ADCETRIS arm and 164 on the placebo arm. Patients eligible for enrollment in the AETHERA trial must have had a history of primary refractory HL, have relapsed within one year from receiving frontline chemotherapy and/or have had disease outside of the lymph nodes at the time of pre-auto-HSCT relapse. Results included:

  • The trial achieved its primary endpoint and demonstrated a significant increase in PFS per independent review facility, with a hazard ratio of 0.57 (95% CI: 0.40, 0.81) and a p-value of 0.001. Median PFS was 43 months (95% CI: 30.4, 42.9) for patients who received ADCETRIS versus 24 months (95% CI: 11.5, not estimable) for patients who received placebo.
  • The most common adverse events (≥20 percent), of any grade and regardless of causality, in the ADCETRIS arm were neutropenia (78 percent), peripheral sensory neuropathy (56 percent), thrombocytopenia (41 percent), anemia (27 percent), upper respiratory tract infection (26 percent), fatigue (24 percent), peripheral motor neuropathy (23 percent), nausea (22 percent), cough (21 percent) and diarrhea (20 percent). The most common adverse events (≥20 percent), of any grade and regardless of causality, in the placebo arm were neutropenia (34 percent), upper respiratory tract infection (23 percent) and thrombocytopenia (20 percent). Sixty-seven percent of patients on the ADCETRIS arm experienced peripheral neuropathy. Of those patients, 85 percent had resolution (59 percent) or partial improvement (26 percent) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range 0.1-138).

There are no post-marketing requirements as part of the U.S. approval. The AETHERA data have also been submitted to both the European Medicines Agency (EMA) and Health Canada requesting marketing authorization.

As part of a broad clinical development program, ADCETRIS is also being evaluated in three additional phase 3 clinical trials, referred to as ECHELON-1, ECHELON-2 and ALCANZA. Enrollment is expected to be completed in ECHELON-1 and ALCANZA during 2015 and in ECHELON-2 during 2016.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including three additional phase 3 studies, in earlier lines of its approved classical HL and sALCL indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma, B-cell lymphomas and mature T-cell lymphomas.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical HL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory HL and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in more than 55 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement,Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING

Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS® (brentuximab vedotin).

Contraindication

ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

  • Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
  • Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
  • Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
  • Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
  • Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
  • Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.
  • Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.
  • Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
  • Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
  • Pulmonary Toxicity: Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, some with fatal outcomes, have been reported. Monitor patients for signs and symptoms of pulmonary toxicity, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.
  • Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
  • Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.

Most Common Adverse Reactions:

ADCETRIS was studied as monotherapy in 160 patients with relapsed classical HL and sALCL in two uncontrolled single-arm trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.

ADCETRIS was studied in 329 patients with classical HL at high risk of relapse or progression post-auto-HSCT in a placebo-controlled randomized trial. The most common adverse reactions (≥20%) in the ADCETRIS-treatment arm (167 patients), regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea.

Drug Interactions:

Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations:

MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.

For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at http://www.seattlegenetics.com/pdf/adcetris_USPI.pdf.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL and non-Hodgkin lymphoma. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells. The Reed-Sternberg cell generally expresses CD30.

According to the American Cancer Society, approximately 9,050 cases of HL will be diagnosed in the United Statesduring 2015 and more than 1,150 will die from the disease.

About Seattle Genetics

Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin) is a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

 

Source: Seattle Genetics