Drugs

Europe Rules Against Amgen’s Tavneos Marketing Authorization

As Amgen continues its bid to prevent the withdrawal of Tavneos (avacopan) in the U.S., European regulators have recommended the revocation of the drug’s marketing authorization, according to a document outlining concerns. Last month, Amgen submitted to FDA new scientific data and analyses as part of its formal request for an FDA hearing, contending that the available evidence satisfies the statutory standard for substantial evidence of effectiveness (see earlier story).

Amgen has argued that the treatment continues to demonstrate a favorable benefit-risk profile for patients with severe active ANCA-associated vasculitis (AAV), a rare and potentially life-threatening autoimmune disease.

However, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) made its recommendation after concluding that serious good clinical practice (GCP) breaches compromised the pivotal ADVOCATE trial used to support the drug's approval.

CHMP said its regulatory review began after EMA received new information in January concerning the sponsor's handling of the ADVOCATE database. The information raised questions about whether study data had been amended after unblinding and whether the changes complied with the prespecified protocol and statistical analysis plan.

According to CHMP, sponsor personnel reviewed unblinded efficacy data after an initial database lock on Nov. 5, 2019, and found that the study had failed to demonstrate superiority at week 52. Nine patients were subsequently re-adjudicated with knowledge of treatment outcomes, after which the primary analysis was rerun and changed from a statistically nonsignificant result to a statistically significant result for superiority at week 52. The sponsor did not disclose the original analysis or the post-unblinding data modifications in the initial marketing application or subsequent post-authorization procedures.

CHMP said the patient-level data and endpoint definitions did not support the sponsor's explanation that the re-adjudication was conducted to correct errors in the original adjudication. The committee concluded that the handling of the data breached GCP principles, including ICH E6 and ICH E9, and that the impact could not be isolated to a particular portion of the study. As a result, CHMP determined that the ADVOCATE trial as a whole could not be considered GCP-compliant or reliable.

The CHMP additionally cited Tavneos' safety profile, including reports of fatal drug-induced liver injury and vanishing bile duct syndrome. Previous periodic safety assessments had resulted in updates to the product information, including more stringent monitoring during the first three months of treatment. With the pivotal efficacy evidence considered unreliable, CHMP concluded that the serious hepatic risks were no longer outweighed by demonstrated benefits.

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

Read more

Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome