November 15, 2017 (Vol. 37, No. 20)

Industry Watch: Researchers See New Era as FDA OKs Kite CAR-T Therapy Yescarta

As Gilead Sciences’ Kite subsidiary won FDA approval for Yescarta™ (axicabtagene ciloleucel)—the agency’s second for a cancer-fighting chimeric antigen receptor T-cell (CAR-T) treatment. Researchers welcomed the news.

“This is the beginning of a new era of cancer therapy,” declared Armin Ghobadi, M.D., an oncologist at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, in a statement.

As with the first-approved CAR-T therapy, Novartis’ Kymriah (tisagenlecleucel), the FDA acted well ahead of schedule. The agency had set a Prescription Drug User Fee Act target decision date for Yescarta of November 29, 2017.

Yescarta’s October 18 approval came 15 days after Gilead completed its approximately $11.9 billion
acquisition of Kite (formerly Kite Pharma).

“By 2025, there will be many approved T-cell therapies for a variety of cancers,” predicted David Maloney, M.D., Ph.D., medical director of cellular immunotherapy at Fred Hutchinson Cancer Research Center and medical director of the Bezos Family Immunotherapy Clinic. “The FDA’s ruling validates the revolution underway in the field of cellular immunotherapy.”

Dr. Maloney said researchers still need to learn why they work in some cancers for some people, and can cause severe, occasionally fatal, side effects in others.

At a list price of $373,000, Yescarta costs 21% less than Kymriah, which is priced at $475,000. Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The approval follows the ZUMA-1 pivotal trial, in which 72% of the 101 patients treated with a single infusion showed an objective response rate, with 51% showing complete remission. However, Yescarta will be sold with a Boxed Warning, as 13% of ZUMA-1 patients experienced grade 3 or higher cytokine release syndrome, and 31% experienced neurologic toxicities.

Discovery & Development: Reports of ADC Progress from Seattle Genetics, Others

An antibody-drug conjugate (ADC) represents, as its name suggests, molecular teamwork. It brings together a monoclonal antibody, a linker, and a therapeutic payload (a cytotoxic agent). Also, ADCs often represent teamwork at the drug-development level, where biotechs and pharmas collaborate to assemble novel ADCs. Collaboration also occurs at the preclinical- and clinical-trial levels of development.

All these kinds of collaboration are evident in recent ADC news. For example, Seattle Genetics, a biotech that specializes in ADCs—and that already has one approved ADC (Adcetris) to its credit—announced that it is pursuing collaborations with GenMab and Astellas Pharma. The work with GenMab involves a Phase II study of tisotumab vedotin as a monotherapy for patients with cervical cancer. The work with Astellas involves a Phase II study of enforumab vedotin as a monotherapy for patients with urothelial cancer.

Seattle is also taking part in clinical collaborations to evaluate SGN-LIV1A, another ADC, in combination therapies against breast cancer. One trial will evaluate the ADC, which targets the LIV-1 protein expressed by most metastatic breast cancers, in combination with Keytruda, an anti-PD-1 therapy marketed by Merck. Another trial will evaluate the ADC followed by standard chemotherapy (doxorubicin and cyclophosphamide) as a neoadjuvant treatment.

Other recent ADC developments include an IND application coming into effect for ImmunoGen’s IMGN632, an ADC for patients with hematological malignancies. NanoValent Pharmaceuticals has licensed its nanoparticle-based ACD platform to Children’s Hospital of Los Angeles, and ADC Therapeutics has secured $200 million to finance clinical development of several ADCs against subtypes of lymphoma and leukemia.

Such developments are helping to drive the growth of the global ADC market, which according to BCC
Research, should reach $4.2 billion by 2021, $2.0 billion of which represents the North American share. The global figure reflects 25.5% annual growth from a 2016 base of $1.3 billion.

Genomics & Proteomics: Clinical Diagnostics Fuses with Genomic Software to Aid Alzheimer’s

Vantari Genetics, a full service clinical diagnostics laboratory, and Translational Software®, Inc. (TSI), a provider of genomic data solutions for clinical decision support, recently announced a partnership aimed at providing genotype testing, actionable genomic information, and custom reporting in support of the Banner Alzheimer’s Institute’s (BAI) GeneMatch registry. GeneMatch is a national program that leverages genetic testing information to recruit participants for Alzheimer’s prevention studies.

“We are grateful to be part of a talented, multidisciplinary team supporting a clinical study infrastructure to help the Banner Alzheimer’s Institute enroll and genotype volunteers to advance Alzheimer’s research,” noted Shaun Opie, Ph.D., chief scientific officer at Vantari Genetics.

In recent years, researchers have identified a variety of genes associated with Alzheimer’s disease. The most common form of the disease is called late-onset Alzheimer’s, which usually begins after age 65 and is associated with a gene called apolipoprotein E (APOE).

Vantari Genetics and TSI are collaborating to support the GeneMatch program through APOE testing and interpreting clinical samples from volunteers interested in participating in community-based Alzheimer’s research opportunities. The raw genomic and molecular data from the tests are analyzed to provide scientific intelligence about the genetic variants of volunteers, which is used to identify study participants at varying degrees of genetic risk for developing Alzheimer’s to match them to available research studies.

The companies will work together to provide BAI with in-depth analysis of the APOE data in multiple, customized formats which will be used to help scientists identify early brain changes in participants and compare the effectiveness of treatments for people with different APOE profiles.

“Our genomic platform is very flexible, which allows us to offer unique genomic testing solutions and data reporting capabilities that can be customized to support single gene testing, in-depth interpretation and analysis, and the integration of independent clinical research,” explained Don Rule, CEO of TSI. “We are pleased to be working with Vantari Genetics to support the important work that BAI is doing to help advance the study of genetic risk for Alzheimer’s.”

Bioprocessing: Ventria Wins $4.2M Gates Foundation Grant toward Biomanufacturing ETEC Therapeutics

Ventria Bioscience said October 23, 2017 it won a $4.2 million grant from the Bill & Melinda Gates Foundation toward the biomanufacturing of new therapeutics targeting enterotoxigenic Escherichia coli (ETEC).

Ventria said the grant will enable it to develop its ExpressTec technology platform for producing potential ETEC treatments.

“This initiative aims to develop a new kind of oral treatment that could be delivered economically on a large scale for use in children or adults,” Ventria President and CEO Scott E. Deeter said in a statement.

ExpressTec is designed to produce recombinant proteins, small peptides, multisubunit molecules, monoclonal antibodies, fusion proteins, and enzymes used in medicine and biotechnology. Instead of using a stainless steel bioreactor, ExpressTec proteins are manufactured within a growing plant using sunlight for an energy source and soil, water, and air as raw materials.

According to Ventria, ExpressTec offers several advantages compared to biomanufacturing with bacterial, yeast, and mammalian cell culture expression systems, transgenic animals, or purification from natural sources. These advantages include higher product yields, the absence of contamination from components of animal or human origin, reduced carbon footprint from the manufacturing process, a “dramatically” lower cost of production, and a broadly flexible platform.

Proteins produced through ExpressTec, Ventria adds, are free of animal, human, and bacterial contaminants; safer and more reliable than blood-derived products; and cost-effective.

“We have proven the effectiveness of our ExpressTec system for biomanufacturing synthetic colostrum proteins, such as lactoferrin and lysozyme,” Deeter added. “This new application in the global fight against ETEC adds to Ventria’s pipeline of projects with the potential to make a real difference in people’s health.”

Doubling Production Capacity

Ventria’s grant from the Gates Foundation comes more than a month after the company broke ground on a $1.5 million, 3,000-square-foot addition to its biomanufacturing and laboratory facilities that the company said would roughly double its recombinant protein production capacity.

Ventria is expanding its molecular biology lab, greenhouses, process development and analytical lab, and processing capacity in Junction City, KS, where the company is headquartered.

The grant also reflects one of the Foundation’s funding priorities—initiatives intended to help reach the goal of ending diarrheal disease deaths in children under five years of age by 2030.

ETEC accounted for an estimated 157,000 deaths per year—9% of all deaths attributed to diarrhea and approximately 1% of all deaths in children 28 days to five years of age, according to the Global Burden of Disease 2010 study.

The World Health Organization reported in 2006 that ETEC is the most common cause of diarrhea in the developing world, with an estimated 280 million to 400 million cases in children aged under 5 years and an additional 100 million episodes in children aged 5 to 14 years.

“ETEC infection cries out for an effective treatment that can be delivered on a large scale in areas struggling with poverty, and the Gates Foundation initiative brings hope to patients and societies afflicted by this disease,” added Ventria CMO Seymour Fein, M.D.

Molecular Diagnostics: Breast Cancer CDx Recieves sPMA Approval

The FDA has granted supplementary premarket approval (sPMA) for Myriad Genetics’ BRACAnalysis CDx®—a companion diagnostic for AstraZeneca’s PARP inhibitor Lynparza® (olaparib)—in patients with HER2-negative metastatic breast cancer. If the test receives full approval, it would be the first and only FDA-approved CDx for use with a PARP inhibitor to identify HER2-negative metastatic breast cancer
patients with a BRCA mutation who would benefit from a PARP inhibitor.

“The acceptance of the sPMA for BRACAnalysis CDx is a significant step towards enabling personalized medicine for patients with metastatic breast cancer,” said Mark C. Capone, president and CEO, Myriad Genetics.  “As the pioneer in companion diagnostics for PARP inhibitors, we are excited to once again partner with AstraZeneca and broaden access to Lynparza for even more patients.”

Myriad said in a statement that it expects the FDA’s priority review to conclude in Q3 of 2018. Myriad’s sPMA filing comes after positive results from a Phase III OlympiAD trial, which demonstrated that Lynparza significantly reduced the risk of disease progression or death in patients with BRCA-mutated, HER2-negative metastatic breast cancer by 42% compared with standard of care therapy. The results of the OlympiAD trial were published in the New England Journal of Medicine in June.

Myriad estimates there are approximately 125,000 patients with metastatic breast cancer who would
immediately qualify for the BRACAnalysis CDx test, followed by 60,000 new patients per year on an
ongoing basis. This test is the result of an ongoing collaboration with AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib.

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