Gevokizumab

Novartis’ office building in Marburg, Germany iStock, TBE The Swiss pharma is returning the anti-TGFβ antibody NIS793 to Xoma Corporation, from which it bought the asset in 2015 for $37 million upfront. Pictured: Novartis’ office in Marburg, Germany/iStock, TBE Novartis is discontinuing the development of the anti-TGFβ antibody NIS793 and is returning it to Xoma Corporation , according to an SEC filing posted Friday. Following the discontinuation, Novartis will stop enrollment into all active clinical studies of NIS793 but will still collect data once these studies have concluded. After returning to Xoma, NIS793 will also remain an investigational compound. “Efficacy and safety have not been established. There is no guarantee that NIS793 will become commercially available,” Xoma wrote in its SEC filing. NIS793 is a fully human and potentially first-in-class monoclonal antibody that works by blocking the TGFβ cytokine, a protein involved in many cancer pathways including metastasis, vascular remodeling and immune evasion. The candidate had previously won the FDA’s Orphan Drug Designation for pancreatic cancer in July 2021. Novartis first gained access to NIS793 in October 2015, when it bought the asset from Xoma for $37 million upfront. The deal also involved up to $480 million in regulatory and commercial milestones. Before ending its development, Novartis was running a Phase III trial for NIS793 in pancreatic ductal adenocarcinoma, testing the candidate in combination with gemcitabine and nab-paclitaxel in the first-line setting. Novartis signed another licensing deal with Xoma in August 2017, gaining worldwide commercial rights to its anti-IL-1β antibody gevokizumab for $31 million. Prior to the deal, the candidate had already failed a Phase III trial for Behcet’s disease uveitis. Novartis is currently developing gevokizumab for the first-line treatment of colorectal cancer, with earlier planned submissions starting in 2026. The pancreatic cancer space has seen major developments lately. Last week, Exelixis stopped and unblinded its Phase III CABINET trial in advanced pancreatic and extra-pancreatic neuroendocrine tumors (NET) following “dramatic improvement” associated with its Cabometyx. There is currently no standard of care for NET patients who progress after initial treatment, representing a large unmet medical need. Cabometyx could potentially present these patients with a strong and effective treatment option. Exelixis will engage regulatory authorities using data from CABINET. In June 2023, Ipsen announced that the FDA had accepted its supplemental New Drug Application, seeking to expand Onivyde (irinotecan liposome injection) into the first-line setting for metastatic pancreatic ductal adenocarcinoma. Its application included data from the Phase III NAPOLI trial, which demonstrated significantly better overall and progression-free survival associated with Onivyde versus nab-paclitaxel and gemcitabine. The FDA’s verdict is due early next year. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

lucarista/Shutterstock Novartis announced the CANOPY-1 Phase III trial of canakinumab failed to meet its primary endpoints when combined with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) plus platinum-based doublet chemotherapy in non-small cell lung cancer (NSCLC). Specifically, the trial did not meet the primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients receiving the combination therapy compared to the placebo cohort that received Keytruda plus platinum-based doublet chemotherapy in patients with previously untreated locally advanced or metastatic NSCLC. The study failed to meet statistical significance for those endpoints. Still, the company did say the study showed potentially clinically meaningful improvements in PFS and OS in pre-specified subgroups based on the baseline inflammatory biomarker, he-CRP, and other biomarker-defined subgroups. They believe this supports the continued study of the drug in lung cancer. “CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications,” said John Tsai, M.D., head of Global Drug Development and chief medical officer, Novartis. “While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer. We share our gratitude and thanks to the CANOPY-1 study patients and clinical investigators for their partnership.” Canakinumab is a human monoclonal antibody that targets human interleukin-1beta (IL-1B) and neutralizes its activity. Data suggests this can inhibit Pro-Tumor Inflammation (PTI) from improving anti-tumor immune response and decreasing tumor cell proliferation, survival, invasiveness, and impairing angiogenesis. In March, the Phase III CANOPY-2 trial also failed to hit the primary endpoint of OS in second- or third-line treatment for patients whose cancer had progressed after previous chemotherapy or immunotherapy. This CANOPY-1 study seems to have similar responses. However, Novartis appears to believe it may still help treat cancer, particularly in earlier disease stages, such as when patients received it post-surgery (adjuvant) or neo-adjuvant (before surgery) in NSCLC patients. The Phase II CANOPY-N trial is evaluating canakinumab in the neoadjuvant setting. It tests the drug alone and in combination with Keytruda in patients with resectable NSCLC before their surgery. CANOPY-A is a Phase III trial evaluating canakinumab in the adjuvant setting after surgical resection and cisplatin-based chemotherapy. The drug was initially developed for atherosclerotic disease, but in 2017, the company found it came with a decreased risk of dying from lung cancer. Novartis and the industry are working to determine if drugs that affect the PTI pathway in NSCLC can be helpful. Novartis is also studying gevokizumab, an antibody against IL-1B, in a Phase I trial. Late last week, Novartis inked an initial deal with Pfizer and BioNTech to expand its fill-and-finish activities for the companies’ COVID-19 vaccine. Novartis will leverage its sterile manufacturing plants at the Novartis Technical Operations site in Ljubljana, Slovenia. It expects to fill at least 24 million doses in 2022.