Arthropathy, Progressive Pseudorheumatoid, of Childhood

iStock, JHVEPhoto Biogen touted strong Q3 sales of its Alzheimer’s drug Leqembi a day after announcing a deal worth up to $1.45 billion with Neomorph to discover and develop molecular glue degraders. Biogen came out on top in the third quarter, exceeding revenue expectations overall and beating Wall Street expectations for Alzheimer’s drug Leqembi, which is slowly beginning to pick up steam after a slow start. The Cambridge, Mass.–based biotech reported $2.5 billion for the third quarter and raised its guidance for the year, expecting earnings per share (EPS) between $16.10 and $16.60, up from between $15.75 and $16.25, according to its report released Wednesday. In June and July 2024, Biogen hit $237 per share, but since then, its shares have been consistently falling. In premarket trading Wednesday morning, the company’s shares were down more than 1%, sitting at $180 per share. Sales of Biogen’s multiple sclerosis drugs were down across the board compared to Q3 2023, with Tecfidera falling to $232.8 million from $239.5 million and Tysabri down to $406.1 million from $456.3 million. On Biogen’s fourth-quarter 2023 earnings call, CEO Chris Viehbacher noted the company’s pivot away from its “legacy multiple sclerosis franchise” as one of five key primary objectives aimed at returning the company to growth. Biogen predicts total 2024 sales to decline by a low-single-digit percentage compared with last year but said it expects these decreases in multiple sclerosis product revenue to be offset by new product launches. One key product launch is that of Leqembi, which received full FDA approval in July 2023 but has struggled to gain traction in the market, in part due to delays in building intravenous infusion infrastructure, diagnostic test requirements and regular brain scans. However, sales have been increasing over the last few quarters, CNBC reported . The anti-amyloid antibody brought in $67 million in sales in the third quarter, exceeding Wall Street predictions of $50 million. Also on the neuro front, Biogen and partner Sage announced they will not pursue further development of recently approved postpartum depression (PPD) drug Zurzuvae in major depressive disorder (MDD). This news was revealed by Sage in its third-quarter earnings report on Tuesday. The companies won approval for Zurzuvae in August 2023 as the first pill for PPD but had hoped to capture a piece of the much broader MDD space. Meanwhile, Biogen became the latest biopharma company to ink a deal in the molecular glue space, tying up with Neomorph in a multi-target research collaboration. The deal, which will see Biogen lay down up to $1.45 billion, is aimed at discovering and developing molecular glue degrader clinical candidates in Alzheimer’s, rare neurological and immunological diseases. The partnership will marry Neomorph’s “leading molecular glue discovery platform” with Biogen’s “deep expertise” in these therapeutic spaces, according to a Tuesday press release . This is the second significant deal struck in molecular glues this week after Novartis announced Monday it would pay Monte Rosa Therapeutics $150 million upfront for the rights to that company’s VAV1-targeting molecular glue degraders. Under the agreement, Monte Rosa is eligible for up to $2.1 billion in development, regulatory and sales milestones.

It’s official: Sage and Biogen will not attempt to get their postpartum depression pill Zurzuvae approved in the broader population of people with major depressive disorder. Sage, which has recently gone through waves of layoffs and scientific setbacks, cited the cost of running and recruiting additional trials for MDD as the reason, and said it would focus solely on postpartum depression. In addition, the company will stop selling its infused PPD drug Zulresso at the end of this year. Zurzuvae had been in development for both PPD and MDD, with Sage promoting the drug’s mechanism of action as different from traditional antidepressants and a way to provide patients with additional options. But after clinical trial data in MDD were mixed, the FDA in August 2023 approved the drug only in PPD and rejected it in major depression, giving the company a historic approval but cutting off a potentially significant revenue stream. In the months following the MDD rejection, Sage has faced numerous setbacks. It has engaged in multiple rounds of layoffs, including a 40% cutback just weeks after the FDA decision. The company cut another 33% of its workforce earlier this month, including leadership positions, and 55% of its R&D staff. One of its other programs, dalzanemdor, also failed in Parkinson’s and Alzheimer’s this year, spurring a pipeline reorganization a few weeks ago. Sage is now focusing on that program’s Huntington’s readout that’s expected before the end of the year, an area where the company changed its pivotal trial’s primary endpoint over the summer. Sage announced the move Tuesday afternoon as part of its third-quarter earnings. Its stock price $SAGE fell about 4% in postmarket trading. As part of the ongoing reorganization, Sage said it has enough runway to operate into 2026.

: SP-624 may treat depression in women by modulating the distinct female genetic profile. Credit: Prathankarnpap/Shutterstock Arrivo BioVentures’ SIRT6 activator SP-624 has been found to significantly reduce symptoms of major depressive disorder (MDD), but only in women. Steve Butts, Arrivo CEO, stated that data from a Phase IIa trial (NCT04479852) showed SP-624 elicited a significant reduction in MDD symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) score. However, reduction was only evident among female patients; for males, no statistically significant difference could be found. Following this trial, the Morrisville, North Carolina-based biotech announced it enrolled its first subject in a Phase I trial (NCT06570369) of the drug for this indication in a 10 October 2024 release. In parallel, Arrivo is running a Phase IIb trial (NCT06254612) specifically focussed on evaluating the drug’s efficacy in female patients as the primary endpoint, which dosed the first patient in April 2024. To explain the disparity, Butts pointed to  research indicating gene expression profiles associated with MDD differ between the sexes. A 2018 meta-analysis published in Biological Psychiatry found that of 706 and 882 genes differentially expressed in men and women with MDD, respectively, only 21 genes in common changed in the same direction—were either up- or downregulated for both sexes. “Our drug is the first epigenetic mechanism being tested in depression that can really test that theory”, claims Butts, adding, “this is the first time that a SIRT6 activator has ever been used in a patient with depression.” See Also: Novartis’ Scemblix gains FDA approval for leukaemia GSK to acquire Chimagen’s CMG1A46 for autoimmune disease SP-624 is a small molecule developed by Sirtsei Pharmaceuticals, a subsidiary of Arrivo, which targets Sirtuin 6 (SIRT6). An NAD-dependent enzyme, SIRT6 modulates gene expression, metabolism, and repair associated with MDD, the activation of which is thought to alleviate depression. Beyond mechanistic differences, MDD also presents at different incidence rates between sexes. As per GlobalData analysis , the prevalence of MDD among females was double that of men in  across the eight major markets (the US, France, Germany, Italy, Spain, the UK, Japan and Canada) 2023. The MDD market is expected to become $9.6bn in size in 2029 in those same eight markets, as per a GlobalData report. GlobalData is the parent company of Pharmaceutical Technology There are so far no marketed therapies indicated exclusively to treat MDD in women, despite its prevalence and distinct genetic profile, and development in the female-oriented clinical space has met resistance. However, in recent years, drugs like Johnson and & Johnson Innovation Medicines’ (J&J) Spravato (esketamine) and Axsome Therapeutics’ Auvelity (dextromethorphan-bupropion) have been approved to treat MDD. J&J also saw some success in the MDD arena earlier this year when its Phase III study with seltorexant improved depressive symptoms in patients as per the MADRS scale. However, not all have been successful. Sage Therapeutics axed 40% of its staff in September 2023 following the rejection of their drug Zurzuvae (zuranolone) for MDD by the US Food and Drug Administration (FDA). The drug is approved to treat postpartum depression (PPD). Earlier this month (17 October 2024), the company fired 55% of the remaining R&D staff to support the drug’s ongoing launch for PPD.