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The FDA closed November’s cycle with five approvals, showing growing momentum in the fight against mitochondrial disease, NPM1-mutant leukemia, severe hypertriglyceridemia, HER2-mutant lung cancer, and IgA nephropathy.
The mix spans both ultra-rare disorders and narrowly defined oncology subsets.
Kygevvi: UCB enters mitochondrial medicine
On November 3, the FDA approved Kygevvi (doxecitine and doxribtimine) from UCB for thymidine kinase 2 deficiency (TK2d) in adults and children with symptom onset at, or before, the age of twelve. It is the first disease-modifying therapy for this fatal mitochondrial myopathy, which, until now, has been characterized by rapid functional decline and reliance on supportive care.
Kygevvi is an oral deoxynucleoside combination designed to bypass the TK2 enzymatic defect and restore mitochondrial DNA replication. This substrate-replacement approach is distinct from previous attempts to modulate mitochondrial energetics and instead addresses the biochemical core of the disease.
Approval was based on three open-label studies (n≈90) compared against external natural-history controls, with no randomised comparator arm. Across UCB’s multi-study dataset, treated patients demonstrated marked reductions in mortality risk versus natural-history controls, along with gains or stabilization in motor milestones, such as sitting and walking.
Safety findings were dominated by gastrointestinal events and transient elevations in liver enzymes.
For UCB, Kygevvi establishes a rare-disease beachhead with clear strategic upside, including potential alignment with newborn screening and earlier diagnostic pathways. Commercial deployment will depend heavily on specialist neuromuscular centers, consistent with UCB’s focus on relevance over scale.
Komzifti: Kura crystallizes the menin opportunity
Komzifti (ziftomenib), from Kura Oncology, was approved on November 13, for adults with relapsed or refractory acute myeloid leukemia harboring susceptible NPM1 mutations and who were lacking satisfactory treatment alternatives. It arrives as one of the first oral menin inhibitors, in a rapidly forming class that now includes Syndax’s Revuforj, which has already been approved for both KMT2A-rearranged and NPM1-mutant leukemias.
Ziftomenib blocks the menin–KMT2A interaction and reverses oncogenic transcriptional programs driven by NPM1 mutations, promoting differentiation with a safety profile distinct from intensive chemotherapy.
The accelerated approval relies on data from the single-arm, 112-patient KOMET-001 phase 1/2 study - CR/CRh was 21–23 percent and OS estimates apply only to responders, who reached a median overall survival of approximately sixteen months.
Differentiation syndrome, cytopenias, and QTc prolongation still require monitoring but were seen to be generally manageable.
Strategically, Komzifti validates Kura’s long-running focus on menin biology and gives the company the chance to define dosing, combinations, and sequencing in a now-rapidly expanding class.
Redemplo: Arrowhead converts RNAi execution into a commercial franchise
On November 18, the FDA approved Redemplo (plozasiran), from Arrowhead Pharmaceuticals, to reduce triglycerides in adults with familial chylomicronemia syndrome. It is the first siRNA therapy cleared specifically for this pancreatitis-prone disorder, following the antisense oligonucleotide Tryngolza as the class-opening FCS treatment, and represents Arrowhead’s transition from platform development to commercial execution.
Plozasiran is a GalNAc-conjugated siRNA that silences APOC3 mRNA in hepatocytes, enabling efficient clearance of triglyceride-rich lipoproteins. Approval is based on PALISADE, a small (n≈75) randomised, placebo-controlled phase 3 trial. TG lowering was the primary endpoint; pancreatitis reduction was a key secondary outcome. Patients achieved a median triglyceride reduction of roughly 80 percent at ten months, translating to a placebo-adjusted effect in the low-60 percent range.
The therapy also reduced pancreatitis events, and improved secondary lipid parameters. Safety was consistent with the RNAi modality, including injection-site reactions and mild metabolic and gastrointestinal events.
The approval strengthens Arrowhead’s cardio-metabolic pipeline and establishes a strong payer narrative built on genetic alignment, quarterly dosing, and robust triglyceride control. With multiple candidates already in late-stage development, Redemplo positions the company as a disciplined and credible commercial RNAi player.
Hyrnuo: Bayer expands its precision lung oncology portfolio
On November 19, the FDA granted accelerated approval to Hyrnuo (sevabertinib), from Bayer, for adults with locally advanced or metastatic non-squamous NSCLC harboring HER2 activating tyrosine-kinase-domain mutations after prior systemic therapy. The approval arrives in a segment that, until recently, had limited targeted options and has only begun to see dedicated HER2 TKIs emerge, following the introduction of Boehringer’s Hernexeos, earlier in the year.
Sevabertinib is an oral, mutation-specific HER2 inhibitor that targets activating kinase-domain mutations, rather than HER2 overexpression or amplification. In the 86-patient, single-arm SOHO-01 study, Hyrnuo achieved a 71 percent objective response rate in the HER2-therapy-naïve patient subgroup, with a median duration of response of 9.2 months.
Adverse events included diarrhea, liver enzyme elevations, QT prolongation, and pneumonitis, all requiring active monitoring.
Commercially, Hyrnuo gives Bayer a relevant precision oncology foothold, as the HER2-mutant lung cancer category matures. With ADC use rising earlier in treatment pathways, an oral, mutation-specific TKI provides differentiation for both specialist and community oncology settings.
Voyxact: Otsuka validates APRIL as a kidney-disease target
The FDA also allowed accelerated approval, on November 25, to Voyxact (sibeprenlimab-szsi) from Otsuka and Visterra, to reduce proteinuria in adults with primary IgA nephropathy at risk of progression. It is the first therapy to neutralize APRIL, a cytokine central to pathogenic IgA production.
Sibeprenlimab is a subcutaneous monoclonal antibody that reduces total and galactose-deficient IgA, lowering immune-complex formation and consequent glomerular injury.
The accelerated approval relies on interim data from the ongoing, randomised phase 3 VISIONARY trial (n≈250), where proteinuria reduction served as the surrogate endpoint.
Interim data showed a placebo-adjusted 51 percent reduction in urinary protein-to-creatinine ratio at nine months, on top of RAS and SGLT2 inhibition. Long-term renal outcomes and eGFR slope data are pending.
Once-monthly at-home administration facilitates adherence and reduces logistical friction that often dog infusion-based therapies.
For Otsuka, Voyxact expands its renal portfolio, with a mechanistically distinctive asset, at a moment when IgAN competition is intensifying. Long-term renal outcomes and eGFR slope effects will determine how APRIL inhibition is positioned, relative to existing and emerging agents.
The Strategic Brief
Komzifti is the clear market mover, giving Kura a credible first commercial foothold in the menin class, while intensifying competitive pressure on Syndax in NPM1-mutant AML.
Voyxact is the other strategic win, validating APRIL as a target and positioning Otsuka early in a renal category that is about to consolidate around mechanistic differentiation.
Kygevvi and Redemplo are high-relevance orphan launches with disciplined commercial scope, while Hyrnuo is a tactical addition for Bayer, strengthening its presence in mutation-specific lung cancer without shifting the broader oncology landscape.
Sources
Kygevvi U.S. FDA prescribing information - Kygevvi - 11/03/2025UCB press release - Kygevvi - 11/03/2025
Komzifti U.S. FDA approval announcement – Komzifti - 11/13/2025Kura Oncology press release - Komzifti - 11/13/2025
Redemplo U.S. FDA prescribing information - Redemplo - 11/18/2025Arrowhead Pharmaceuticals press release - Redemplo - 11/18/2025
Hyrnuo U.S. FDA accelerated approval announcement - Hyrnuo - 11/19/2025Bayer press release – Hyrnuo - 11/19/2025
Voyxact U.S. FDA accelerated approval announcement - Voyxact - 11/25/2025Otsuka press release - Voyxact - 11/25/2025
