Sertraline Hydrochloride

Moderna's scrapped mRNA plant in Japan, a negative opinion on Lundbeck and Otsuka's Rexulti, and Pfizer's finalized cancer drug deal with 3SBio made our news this week. Moderna has scrapped plans to build an mRNA plant in Japan. Otsuka and Lundbeck's proposal for Rexulti as part of a PTSD treatment was rejected by an FDA advisory committee. Pfizer's PD-1xVEGF deal with 3SBio includes an option agreement. And more.1. Moderna, facing uncertain business environment, scraps plan to establish mRNA plant in JapanModerna has abandoned a plan to construct an mRNA drug substance plant in Fujisawa, Japan. The decision comes “in light of changes in the business environment both globally and in Japan,” the company said. Moderna pledged to continue providing a “stable supply of vaccines to the country using its global manufacturing network.”2. Lundbeck, Otsuka's PTSD bid for Rexulti dealt a setback at FDA advisory committeeAn FDA advisory committee voted 10 to 1 against recommending Lundbeck and Otsuka’s Rexulti, used alongside Viatris’ Zoloft, for treating post-traumatic stress disorder. Even though several experts hinted that the combo may be effective because of a consistent favorable trend observed across trials, they eventually agreed that the evidence wasn't sufficient to draw a conclusion.3. Pfizer finalizes 3SBio PD-1xVEGF deal with China option agreement (release, PDF)Pfizer has finalized its licensing deal for 3SBio’s PD-1xVEGF candidate SSGJ-707. Other than the ex-China portion of the deal featuring a $1.25 billion upfront payment, Pfizer also gained an option to extend the license to cover China. Upon exercise of the option, Pfizer will pay the Chinese company up to $150 million in additional fees.4. TCG Labs Soleil raises $400M for single-asset biotechs, expands R&D footprint to ChinaTCG Labs Soleil has secured $400 million, which is the exact same size as its inaugural fund last year. TCG Labs Soleil runs a venture-biotech model with its own R&D hub, aiming to help single-asset biotechs move through clinical proof of concept. The organization has established an R&D site in Shanghai.5. China’s Novatim licenses BCMA/CD19 CAR-T to Factor’s Erigen (release, Chinese)China’s Novatim has licensed a BCMA/CD19 dual-targeting CAR-T to Erigen, a company associated with Factor Bioscience. The deal includes $15 million in near-term development milestones, with the total milestone payments potentially reaching $1.32 billion. The candidate, coded KQ-2003, is currently in a phase 1b test in China.Other News of Note:6. Orient Pharma, AvKARE recall nearly 80K bottles of cholesterol drug over impurity concerns7. Kyowa, Amgen and Sanofi back push to change websites that miss the mark on women's health8. Roche's Flatiron Health triples cancer network size across UK, Germany and Japan9. Korean CRO CorestemChemon inks collaboration to expand into organoids and transcriptomics

Following the negative vote, analysts at Jefferies lowered their 2027 revenue projection for Otsuka by 1%, while the consensus estimate dropped by 2%. The prospect of Lundbeck and Otsuka’s Rexulti becoming part of a new treatment for post-traumatic stress disorder (PTSD) appears more unlikely after a Friday meeting of experts in the field.An advisory panel to the FDA on Friday overwhelmingly recommended against Rexulti’s proposed PTSD use alongside Viatris’ Zoloft (sertraline), saying that existing clinical data have not established the efficacy of the combo. The vote was 10 to 1, with the single vote in favor coming from a patient representative.The near-unanimous vote came as a bit of a surprise given that several experts hinted that the combo may be effective because of a consistent favorable trend seen across clinical studies. But they eventually agreed that there simply isn’t enough evidence to make a conclusion.The FDA typically follows opinions of its advisory committees, even though it isn’t obligated to do so. In this case, FDA reviewers have their own doubts around the Rexulti-Zoloft regimen, having flagged “discordant results” from two phase 3 trials in briefing documents ahead of the meeting.Following the negative vote, analysts at Jefferies lowered their 2027 revenue projection for Otsuka by 1%, while the consensus estimate dropped by 2%.At the center of the issue is a “clearly and convincingly negative” phase 3 study that showed no improvements for Zoloft and Rexulti, dosed at either 2 mg or 3 mg in separate patient cohorts, versus Zoloft alone, according to the FDA. A second phase 3 trial, which used flexible dosing of Rexulti in one group, was positive.To bolster their case, Lundbeck and Otsuka used an exploratory phase 2 analysis, which demonstrated superiority of the combo in a retrospective review but not under the study’s original statistical design.The drugmakers argued that Rexulti and Zoloft showed similar reductions in the severity of PTSD symptoms across the three trials, regardless of one study failing to reach statistical significance. But the FDA advisors couldn’t see past the negative trial.“I agree that one [study] is very strongly positive. One is strongly null,” Brian Shiner, M.D., from Dartmouth College said during Friday’s deliberation. “Considering them together, I don't know whether the combination of [Rexulti] plus [Zoloft] is better than [Zoloft] alone, because of the discordance.” The FDA staff conducted multiple exploratory analyses, dissecting the trial data by different factors such as sex and prior treatments. In the end, they couldn’t identify an explanation for the differing outcomes.University of California Los Angeles expert Walter Dunn, M.D., Ph.D., suspected that one phase 3 was positive because it enrolled a more treatment-resistant population. These patients were less responsive to Zoloft monotherapy, potentially handing the Rexulti combo a bigger effect size, he suggested.Dunn’s hypothesis, which was echoed by other committee members, points a finger at Lundbeck and Otsuka’s trial design.As the FDA noted, antipsychotic drug trials typically adopt an “adjunctive treatment” pathway in which only participants with a partial response to one drug receive a second drug. This model allows the experimental combo to be studied in patients who have an inadequate benefit from approved monotherapy. But the Rexulti phase 3 trials gave the drug concurrently with Zoloft, with no requirement of prior inadequate response to monotherapy.While plausible, there’s no conclusive data to back Dunn’s hypothesis. And the FDA experts acknowledged the difficulty in conducting PTSD trials.“My overall assessment is that this is a heterogeneous condition, and that even by chance, trials could enroll quite different populations with respect to the underlying clinical heterogeneity,” Pamela Shaw, Ph.D., a biostatistician with Kaiser Permanente, said at the meeting. “We at this point know that there’s wide variation in […] how people with PTSD respond to sertraline, that is, at least to my understanding at this point, not explainable or predictable." Dunn, a psychiatrist at West Los Angeles Veterans Affairs Medical Center, also questioned whether the magnitude of improvements shown by Rexulti and Zoloft, even if statistically significant, were clinically meaningful to be worthy of the potential adverse outcomes from the addition of an antipsychotic.The FDA has not decided on Rexulti-Zoloft in PTSD. The agency has overruled advisory committee recommendations in the past, most recently in the case of UroGen’s bladder cancer drug Zusduri.Otsuka and Lundbeck “remain fully committed to collaborating with the FDA as they complete their review of this application,” Otsuka’s chief medical officer, John Kraus, M.D., Ph.D., said in a statement Friday. “We continue to believe in [Rexulti]’s potential to make a meaningful difference as a treatment option for the PTSD patient population.”