Sanofi Advances wAIHA Program as Rilzabrutinib Receives Breakthrough and Orphan Status; Lilly Moves to Acquire Orna Therapeutics, Expanding Cell Therapy Portfolio; Roche Announces Key PPMS Trial Success for Fenebrutinib; Priovant’s Brepocitinib Demonstrates Strong Potential in Phase 2 Cutaneous Sarcoidosis Study; AstraZeneca’s DATROWAY Grants US Priority Review for 1L mTNBC Indication in Patients not Eligible for Immunotherapy

Sanofi’s Rilzabrutinib Granted Breakthrough and Orphan Designations for wAIHA

Rilzabrutinib (WAYRILZ) by Sanofi (EPA: SAN) recently achieved two major regulatory milestones: FDA Breakthrough Therapy Designation in the U.S. and Orphan Drug Designation by the Japanese Ministry of Health, Labour and Welfare for the treatment of warm autoimmune hemolytic anemia (wAIHA). wAIHA is a rare, life-threatening autoimmune disorder where the immune system incorrectly identifies red blood cells as foreign and destroys them, primarily in the spleen and liver. This leads to profound anemia, fatigue, and potential cardiovascular failure. Currently, the standard of care relies on corticosteroids or off-label immunosuppressants, which often provide only temporary relief and carry a heavy burden of long-term side effects.

Rilzabrutinib is a first-in-class, oral, reversible covalent Bruton’s tyrosine kinase (BTK) inhibitor. While traditional BTK inhibitors are often used in oncology, rilzabrutinib uses Sanofi’s proprietary “Tailored Covalency” technology to selectively modulate multiple immune cells, including B cells and macrophages, without permanently binding to its target. This selective inhibition blocks the signaling pathways that drive autoantibody production and the subsequent destruction of red blood cells.

The designations are anchored by promising data from the ongoing Phase 2b LUMINA 2 study. In this trial, rilzabrutinib demonstrated a rapid and durable increase in hemoglobin levels, with some patients achieving normal levels as early as week 24. Furthermore, the drug showed a significant reduction in biomarkers of hemolysis and inflammation. The safety profile remained favorable, with most adverse events being mild to moderate. With Breakthrough status, Sanofi will benefit from intensive FDA guidance on the ongoing Phase 3 LUMINA 3 trial, potentially shortening the timeline to bring the first specifically indicated oral treatment to the wAIHA community.

Lilly Plans Acquisition of Orna Therapeutics to Boost Cell Therapy Pipeline

In a move to dominate the next frontier of genetic medicine, Eli Lilly (NYSE: LLY) signed a definitive agreement to acquire Orna Therapeutics in a deal valued at up to $2.4 billion. This acquisition centers on Orna’s breakthrough “circular RNA” (oRNA) technology, which represents a massive leap over the linear mRNA platforms used in current vaccines. Linear mRNA is susceptible to rapid degradation by cellular enzymes; however, oRNA is engineered in a closed-loop structure, making it more stable and allowing it to produce therapeutic proteins for significantly longer periods.

The primary driver of the acquisition is Orna’s in vivo CAR-T platform. Standard CAR-T therapy currently requires an expensive and arduous “ex vivo” process: a patient’s T-cells are harvested, shipped to a specialized lab, genetically modified to recognize cancer or autoimmune markers, and then re-infused. This process can take weeks and cost hundreds of thousands of dollars. Orna’s technology aims to bypass this entirely by using specialized lipid nanoparticles (LNPs) to deliver oRNA directly to the patient’s immune cells inside their own body.

Lilly’s immediate focus is the lead program ORN-252, a clinical-ready, CD19-targeting in vivo CAR-T therapy. While CD19-targeting is a proven strategy in blood cancers, Lilly is prioritizing its use to “reset” the immune system in patients with B-cell-driven autoimmune diseases. By destroying the self-reacting B-cells through a simple injection, this therapy could offer a “one-and-done” functional cure for conditions like systemic lupus or rheumatoid arthritis. This acquisition signals a transition for Lilly, expanding its portfolio beyond obesity and diabetes into high-growth areas of cell engineering and immunology.

Roche Reports Positive Results for Fenebrutinib in Primary Progressive Multiple Sclerosis

Roche (SWX: ROG) and its subsidiary Genentech reported landmark results from the Phase 3 FENtrepid trial, marking the first scientific breakthrough for the Primary Progressive Multiple Sclerosis (PPMS) community in over ten years. PPMS is a particularly debilitating form of MS characterized by a steady worsening of neurological function from onset, without the relapses and remissions seen in other forms. Until now, Ocrevus (ocrelizumab) was the only approved therapy for PPMS, but its efficacy in stopping long-term disability progression has remained limited.

The FENtrepid study evaluated fenebrutinib, an oral, brain-penetrant BTK inhibitor, against Ocrevus. The trial met its primary non-inferiority endpoint, demonstrating that fenebrutinib was at least as effective as Ocrevus in reducing disability. Specifically, fenebrutinib showed a 12% numerical reduction in the risk of 12-week composite confirmed disability progression (cCDP12). What makes fenebrutinib truly significant is its mechanism: unlike Ocrevus, which primarily depletes B-cells in the blood, fenebrutinib crosses the blood-brain barrier to target both B-cells and microglia (immune cells in the brain) that drive the “smoldering” inflammation responsible for neurodegeneration.

Clinical data further highlighted fenebrutinib’s impact on upper limb function, with a post-hoc analysis showing a 26% reduction in the risk of worsening on the 9-hole peg test. This is a vital outcome for PPMS patients, who rely on hand and arm dexterity for daily independence. While the trial noted higher rates of transient liver enzyme elevations in the fenebrutinib group, all cases resolved upon discontinuation. Roche plans to seek global regulatory approval for fenebrutinib as a high-efficacy, oral alternative that targets the biological drivers of progression within the central nervous system.

Priovant Reports Encouraging Phase 2 Data for Brepocitinib in Cutaneous Sarcoidosis

Priovant Therapeutics, a joint venture between Roivant (NASDAQ: ROIV) and Pfizer (NYSE: PFE), announced “watershed” Phase 2 results for brepocitinib in the treatment of cutaneous sarcoidosis. Sarcoidosis is an inflammatory disease that causes granulomas to form in various organs; when it affects the skin, it can lead to painful, disfiguring lesions and permanent scarring. Despite the severity of the condition, there have been zero industry-sponsored clinical trial successes and no FDA-approved therapies specifically for skin sarcoidosis until now.

Brepocitinib is a potent, oral dual JAK1/TYK2 inhibitor. By blocking both Janus Kinase 1 and Tyrosine Kinase 2, the drug inhibits the wide array of cytokines (such as IL-12, IL-23, and interferon-gamma) that are thought to drive granuloma formation. In the BEACON study, the 45 mg dose of brepocitinib achieved an unprecedented 22.3-point mean improvement in the Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI-A) score at week 16, compared to a negligible 0.7-point improvement in the placebo group (P < 0.0001).

The secondary endpoints were equally impressive: 100% of patients on the high-dose arm achieved a clinically meaningful response (defined as a 10-point reduction in CSAMI-A), and 69% reached the “gold standard” of “Clear” or “Almost Clear” skin on the Investigator’s Global Assessment (IGA). Patients also reported significant improvements in their quality of life and skin-related distress. Given the lack of existing treatments and the “clean” safety profile observed in the study, Priovant is rapidly advancing brepocitinib into a pivotal Phase 3 program, which could finally offer a transformative option for the thousands of patients suffering from this disfiguring disease.

AstraZeneca’s DATROWAY Awards Priority Review in the US for Initial Treatment of mTNBC in Immunotherapy-ineligible Patients

The FDA has granted Priority Review to AstraZeneca (LON: AZN) and Daiichi Sankyo’s (TYO: 4568) supplemental Biologics License Application (sBLA) for DATROWAY (datopotamab deruxtecan) as a first-line treatment for metastatic triple-negative breast cancer (mTNBC). Triple-negative breast cancer is the most aggressive form of the disease, lacking the three most common receptors (estrogen, progesterone, and HER2) used for targeted therapy. While immunotherapy has improved outcomes for some, roughly 70% of patients are ineligible for current immune-based treatments due to low PD-L1 expression or other clinical factors, leaving them with chemotherapy as their only first-line option.

DATROWAY is a TROP2-directed antibody-drug conjugate (ADC). It consists of a monoclonal antibody that targets the TROP2 protein (highly expressed in TNBC) linked to a potent topoisomerase I inhibitor “payload.” This allows the drug to deliver a lethal dose of chemotherapy directly into the cancer cells while minimizing damage to healthy tissue. The Priority Review is based on the Phase 3 TROPION-Breast02 trial, which demonstrated that DATROWAY is the first and only medicine to significantly improve overall survival (OS) compared to standard chemotherapy in this specific patient population.

The trial data showed a 5.0-month improvement in median OS and nearly doubled the time patients lived without disease progression (10.8 months vs. 5.6 months). DATROWAY also achieved a much higher objective response rate (62.5% vs. 29.3%) and demonstrated greater durability of response. With Priority Review and evaluation under Project Orbis (an international collaborative review), DATROWAY is on an accelerated path toward mid-2026 approval. This would establish it as the new first-line standard of care for immunotherapy-ineligible mTNBC patients, replacing traditional chemotherapy with a more effective, better-tolerated targeted agent.