Autologous Epstein-Barr virus-specific T-cell therapy(Atara Biotherapeutics, Inc.)

When patients undergo transplant procedures, the immunosuppressive drug regimen that prevents rejection of the organ or stem cells can lead to a potentially deadly complication. This week, the European Commission approved a cell therapy to treat this rare condition. The regulatory decision also makes the Atara Biotherapeutics product the first allogeneic cell therapy approved anywhere in the world. The Atara product, tabelecleucel, addresses a blood cancer called Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+PTLD). In healthy people, T cells keep Epstein-Barr virus in check. EBV+PTLD develops when the suppressed immune system can’t stop this virus from infecting white blood cells, which then grow uncontrollably. European marketing authorization for the Thousand Oaks, Calfornia-based company’s cell therapy covers the treatment of relapsed or refractory EBV+PTLD in adults and children age 2 and older. The Atara cell therapy, brand name Ebvallo, is made from bioengineered T cells from healthy donors. Unlike the first generation of cell therapies—made in a lengthy process involving harvesting a patient’s T cells, engineering them in a lab, and then reinfusing them into the patient—Atara’s allogeneic cell therapy offers patients and clinicians a ready-to-use option. European approval of Ebvallo covers those who have received at least one prior therapy, such as Rituxan, a blood cancer drug that is a standard treatment for EBV+PTLD. For solid organ transplant patients, chemotherapy counts as a prior therapy. Atara last year reached a licensing agreement with French healthcare company Pierre Fabre, which will lead commercialization of the cell therapy in Europe and certain emerging markets. That deal put Atara in line for up to $348 million in milestone payments tied to regulatory and commercial milestones. Ebvalla has yet to be submitted to the FDA for review, though the company has met with the agency to discuss the requirements for such a filing. Atara has said it is seeking a partner for potential commercialization of the cell therapy in the U.S. The European nod for Ebvallo was one of several notable regulatory developments on both sides of the Atlantic this past week. Here’s a recap of biotech regulatory news: —Reform of the FDA’s accelerated approval program is part of a wide-ranging fiscal 2023 spending bill that’s working its way through Congress. In addition to giving the FDA more money, the omnibus bill could also enable the agency to require that drugmakers start confirmatory testing of a drug before they can receive an accelerated approval. The legislation also calls for companies to submit “timely reports” at least every six months until the confirmatory study is completed or terminated. —Actemra, a Roche drug whose approved indications include rheumatoid arthritis, has won an additional FDA approval as a Covid-19 treatment. The drug’s latest regulatory green light covers hospitalized adults who are being treated with systemic corticosteroids and require breathing help from supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The FDA granted Actemra emergency use authorization for Covid-19 in June 2021. The approval makes the drug, dosed as a single 60-minute infusion, the first monoclonal antibody approved by the agency for treating Covid-19. —The FDA approved the first gene therapy for bladder cancer. The Ferring Pharmaceuticals product, Adstilarin, delivers genetic instructions to the cells of a patient’s bladder wall that get them to produce large quantities of interferon-alpha 2b, a therapeutic protein with anti-cancer properties. An earlier application seeking regulatory approval of the gene therapy was turned down in 2020 due to manufacturing problems. Ferring said Adstilarin will become available in the second half of next year after the company expands its manufacturing capacity. —Lynparza, a cancer drug marketed by partners AstraZeneca and Merck, has been approved in Europe as a first-line treatment metastatic for castration-resistant prostate cancer (mCRPC) in those for whom chemotherapy is not likely to offer benefit. The European Commission decision covers the use of the drug in combination with the cancer therapy abiraterone as well as the steroids prednisone or prednisolone. Lynparza is what’s called a PARP inhibitor. The drug interferes with the PARP enzyme, which cancer cells rely on to repair DNA damage. The drug’s FDA approvals span cancers of the ovary, breast, pancreas, and prostate. Under the collaboration agreement, the latest approval for the drug triggers a $105 million milestone payment from Merck to AstraZeneca. —The FDA lifted its partial clinical hold on tests of Bluebird Bio’s sickle cell disease gene therapy in patients younger than 18. Last year, the agency placed the partial hold on the therapy, lovotibeglogene autotemcel (lovo-cel), after an adolescent patient developed anemia following dosing of the experimental treatment. During the recent annual meeting of the American Society of Hematology, data were presented from an investigation of that case and another one in an adult patient who developed persistent anemia after receiving lovo-cel. The case studies showed that both patients had a certain alpha-thalassemia trait, a genetic mutation that can lead to anemia. Bluebird said this specific genotype has since been added to exclusion criteria for ongoing tests of the gene therapy. —Entrada Therapeutics’ plan to begin clinical testing of its experimental treatment for Duchenne muscular dystrophy has hit a setback. The FDA placed a clinical hold on the Boston company’s investigational new drug application, a move that is increasingly common when the agency encounters new therapeutic modalities. Entrada is developing a new class of drugs based on a technology platform that enables delivery of a wide range of therapeutics into cells. Earlier this month, Vertex Pharmaceuticals committed $250 million to begin a research alliance leveraging Entrata’s technology to develop drugs for a different muscle disorder, myotonic dystrophy type 1. —Tymlos, a Radius Health osteoporosis drug for women, is now approved for men. The FDA expanded the drug’s label to include increasing the bone density in men with osteoporosis who are at high risk of fracture. Tymlos, a peptide drug that targets a pathway involved in bone formation, won its initial FDA approval in 2017. After eight years as a public company, Radius Health was taken private earlier this year by two private equity firms. —Vraylar, a blockbuster AbbVie mental health drug, now has a new indication. The FDA approved the once-daily capsule for use in addition to antidepressants as a treatment for major depressive disorder. The drug’s previous approvals span bipolar disorder, schizophrenia, and bipolar depression. This year, the drug tallied $1.4 billion in revenue through the third quarter, an 18.8% increase compared to the same period in 2021.