AVEO Pharmaceuticals, Inc.

FRIDAY, Sept. 20, 2024 -- For patients with metastatic renal cell carcinoma (mRCC) and progression during or after one to two prior lines of therapy, including one immune checkpoint inhibitor (ICI), tivozanib has efficacy, according to a study published online Sept. 13 in The Lancet to coincide with the annual meeting of the European Society for Medical Oncology, held from Sept. 13 to 17 in Barcelona, Spain. Toni K. Choueiri, M.D., from the Dana-Farber Cancer Institute and Harvard Medical School in Boston, and colleagues examined the outcomes of tivozanib-nivolumab versus tivozanib monotherapy in patients with mRCC who progressed following one or two lines of therapy in the post-ICI setting in a randomized, phase 3 trial. Patients were randomly allocated to tivozanib plus nivolumab or tivozanib monotherapy (171 and 172 patients, respectively) and were followed for a median of 12.0 months. The researchers found that median progression-free survival was 5.7 and 7.4 months with tivozanib-nivolumab and tivozanib monotherapy, respectively, which was not significantly different. Among 244 patients with ICI as immediate prior therapy, median progression-free survival was 7.4 and 9.2 months with tivozanib-nivolumab and tivozanib monotherapy, respectively. With non-ICI as the most recent therapy, median progression-free survival was lower, with no significant difference seen between the groups (both 3.7 months). Serious adverse events occurred in 32 and 37 percent of patients who received tivozanib-nivolumab and tivozanib monotherapy, respectively. "These results demonstrated clinical activity of tivozanib monotherapy as a second line treatment option, and rechallenging with nivolumab in the setting of prior exposure to ICI is not warranted," the authors write. Several authors disclosed ties to pharmaceutical companies, including Aveo Pharmaceuticals, which manufactures tivozanib and funded the study.

FDA's citations for Hengrui, Sanofi's $437 million expansion in India, and closure of the Singapore biotech Aslan made our news this week. A 10-page Form 483 has detailed the shortfalls at Hengrui Pharma's PD-1 plant behind a recent FDA rejection. Sanofi is investing heavily to expand its global capacity center in India. Singapore biotech Aslan Pharma is winding down. And more. 1. Behind Hengrui's surprise FDA rejection: Scathing Form 483 lists litany of shortfalls at PD-1 drug plant The Form 483 that led to the FDA’s rejection of Jiangsu Hengrui Pharma and Elevar Therapeutics’ PD-1 inhibitor camrelizumab included 10 observations issued to Hengrui’s subsidiary, Suzhou Suncadia Biopharmaceuticals. In addition, the FDA has upgraded a prior eight-observation Form 483 into a warning letter for Hengrui’s small-molecule facility in Lianyungang, China. 2. Sanofi to more than double its workforce at Hyderabad site with $437M expansion: reports Sanofi will invest 400 million euros through the end of the decade to expand its global capacity center in Hyderabad, India. Sanofi plans to grow the site’s workforce to 2,600 people—from 1,000 today—in two years, making it the largest of the company’s four global capacity hubs. The site will grow its digital capabilities, including utilizing artificial intelligence tools. 3. Aslan’s dream of challenging Dupixent dies as cash-strapped biotech winds down Aslan Pharmaceuticals, one of the first Singapore-based biotechs to rise to the global stage, is shutting down. With $18.4 million in cash as of the end of March, the company has decided to file for liquidation and has let go all its staffers. The biotech’s stock price was once worth nearly $390 a piece at its peak in 2018 until its lead program, the pan-HER drug varlitinib, failed. Before the decision to close doors, Aslan received a delisting warning from Nasdaq as its stock price had been trading below the $1 bid price. 4. J&J’s CAR-T partner Legend Biotech reportedly receives buyout offer Legend Biotech reportedly received a takeover bid and has tapped Centerview Partners as a financial adviser, according to StreetInsider. The stock price surged for Legend and its former parent and largest shareholder, GenScript. The report came a few weeks after two House lawmakers had requested an intelligence briefing on GenScript and its related operations, including Legend. 5. SK inks $572M deal for Full-Life prospect, advancing push to become Asia’s radiopharma leader SK Biopharmaceuticals inked a $571.5 million biobucks deal to license an NTSR1-directed radionuclide-drug conjugate candidate, FL-091, from Full-Life Technologies. NTSR1 is overexpressed in colorectal, breast, pancreatic, and head and neck cancers. The Korean company outlined plans a year ago to expand in oncology and identified radiopharmaceuticals as one of the modalities driving the push. Other News of Note: 6. Sotio taps Biocytogen to create bispecific ADCs in $326M deal 7. Aveo spins a silver lining in failed trial of kidney cancer drug Fotivda 8. BeiGene brings on Merck veteran as new CFO (release)

Aveo Oncology's phase 3 trial of Fotivda in combination with Bristol Myers Squibb's Opdivo came up short. But the Korean company is touting the results of the kidney cancer drug from the control arm. The addition of Bristol Myers Squibb’s Opdivo to a low dose of Aveo Oncology’s Fotivda failed to extend the time before tumor progression or death in kidney cancer patients who had tried an immune checkpoint inhibitor (ICI). Despite the failure of the phase 3 trial on its primary endpoint of progression-free survival (PFS) for the combo, Aveo is touting the results from the control arm where a standard dose of Fotivda as a monotherapy showed a clinically meaningful outcome in median PFS. Approved in Europe in 2017 and in the United States in 2021 for third-line treatment of kidney cancer, Fotivda showed its ability to excel in an earlier line of therapy, according to the trial’s lead investigator. “The PFS and safety results from the control arm support tivozanib as an effective and well-tolerated treatment option in the second-line following an ICI combination as prior systemic therapy,” Toni Choueiri, M.D., a professor of medicine at Harvard Medical School said in a release. In the TiNivo-2 phase 3 trial, a 0.89 mg dose of Fotivda was combined with Opdivo. In the control arm, a standard 1.34 mg dose of Fotivda was used. Aveo did not reveal data from the study, saying it would provide more details at an upcoming medical meeting. The results build on the TIVO-3 clinical trial, which evaluated Fotivda in the third-line setting against Bayer’s Nexavar and set up the VEGFR tyrosine kinase inhibitor for its approvals. “While the addition of an ICI to low dose Fotivda did not improve PFS outcomes after prior ICI, we consider the control arm data an important, evidence-based and clinically meaningful contribution to the oncology community treating relapsed or refractory advanced RCC following front-line ICI combinations,” Michael Bailey, Aveo’s CEO, said. It is the second phase 3 trial to show that there is no clinical benefit from “rechallenging RCC patients with immunotherapy after receiving ICI beyond progression on previous ICIs,” Aveo added. In October 2022, Aveo was acquired by another Korean company, LG Chem, which paid a 43% premium of $566 million for the buyout to gain Fotivda and Aveo’s portfolio of other cancer candidates. On its way to gaining approval of Fotivda nine years after its original submission to the FDA, Aveo had to clear multiple hurdles including investor lawsuits, failed trials, an SEC investigation and two rejections from the U.S. regulator.