Sanofi’s Venglustat Gains US Breakthrough Therapy Nod, Boosting Hope for Type 3 Gaucher Disease; Rhythm Pharmaceuticals Expands IMCIVREE Label with FDA Approval in Hypothalamic Obesity; FDA Approves LYNAVOY for Cholestatic Pruritus in PBC Patients; FDA Greenlights J&J/Protagonist’s ICOTYDE, Redefining First-Line Systemic Therapy for Plaque Psoriasis; Novartis Strengthens its Breast Cancer Portfolio Through Acquisition of a Pan-mutant PI3Kα Inhibitor

Sanofi Wins US Breakthrough Therapy Tag for Venglustat in Type 3 Gaucher Disease

The US Food and Drug Administration (FDA) has awarded Breakthrough Therapy designation to venglustat, an investigational oral glucosylceramide synthase inhibitor (GCSi), for treating neurological symptoms associated with type 3 Gaucher disease (GD3), a rare lysosomal storage disorder.

This designation is supported by findings from the Phase 3 LEAP2MONO trial (NCT05222906), where patients treated with venglustat showed statistically significant improvements in neurological outcomes. These were measured using a composite global test score incorporating ataxia (mSARA) and cognitive function (RBANS), compared to patients receiving enzyme replacement therapy (ERT) with imiglucerase (p=0.007). Venglustat was generally well tolerated, with no new safety concerns identified relative to earlier studies. Reported adverse events included headache (14.3% with venglustat vs. 18.2% with ERT), nausea (14.3% vs. 4.5%), splenomegaly (14.3% vs. 0%), and diarrhea (14.3% vs. 0%).

Previously, venglustat received Fast Track designation from the FDA for GD3, along with orphan drug status in the US, EU, and Japan. Sanofi plans to initiate global regulatory submissions for venglustat in GD3 in 2026.

The FDA’s Breakthrough Therapy designation aims to accelerate the development and review of drugs intended for serious or life-threatening conditions. To qualify, therapies must show early clinical evidence indicating the potential for substantial improvement over existing treatment options on meaningful clinical endpoints.

Rhythm Pharmaceuticals Secures FDA Approval for IMCIVREE in Acquired Hypothalamic Obesity

Rhythm Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration has approved a broader indication for IMCIVREE. The therapy is now authorized for the treatment of individuals with acquired hypothalamic obesity (HO).

Acquired HO is a rare condition marked by rapid and persistent weight gain resulting from damage or dysfunction of the hypothalamus. Under the expanded label, IMCIVREE can be used to support weight reduction and long-term weight management in both adults and children aged 4 years and older with this condition.

The disorder is linked to disruptions in the melanocortin-4 receptor (MC4R) pathway, which regulates hunger, energy expenditure, and body weight. Acquired HO often develops following hypothalamic injury, frequently associated with tumors or their treatment. Based on available data sources, Rhythm estimates that around 10,000 individuals in the U.S. are affected by this condition.

The approval is based on results from the Phase 3 TRANSCEND trial, a global study involving 142 patients with acquired HO. The trial successfully met its primary endpoint, demonstrating a statistically significant placebo-adjusted reduction in body mass index (BMI) of 18.4%. Patients treated with setmelanotide (n=94) experienced an average BMI reduction of 15.8%, compared to a 2.6% increase in the placebo group (n=48) over 52 weeks (p<0.0001). The treatment showed a favorable safety profile, with the most common side effects, occurring in more than 20% of participants, being skin hyperpigmentation, nausea, vomiting, and headache.

IMCIVREE is already approved in the U.S. and Europe for adults and children aged 2 years and above with certain rare genetic forms of obesity, including those associated with Bardet-Biedl syndrome (BBS) and deficiencies in POMC, PCSK1, or LEPR.

Rhythm Pharmaceuticals has stated its commitment to ensuring patient access, with IMCIVREE now immediately available in the U.S. The company also offers support through its Rhythm InTune program, which provides education, insurance assistance, injection training, and ongoing guidance for patients and healthcare providers throughout the treatment journey.

FDA Clears GSK’s LYNAVOY for Cholestatic Pruritus in PBC Patients

GSK plc has announced that the U.S. Food and Drug Administration has approved LYNAVOY (linerixibat) for treating cholestatic pruritus in adults with Primary Biliary Cholangitis. As an ileal bile acid transporter (IBAT) inhibitor, LYNAVOY targets multiple underlying causes of chronic itching and becomes the first therapy authorized in the United States for this condition.

Earlier, on 9 March, GSK revealed a licensing deal under which Alfasigma S.p.A. will obtain global exclusive rights to develop, produce, and commercialize linerixibat. The agreement is still in progress and awaits standard regulatory approvals, including clearance under the Hart-Scott-Rodino Act.

Cholestatic pruritus is a severe internal itching sensation affecting up to 89% of individuals with PBC, a rare autoimmune liver disorder that may progress to liver failure. The condition can significantly impact daily life, causing sleep disruption, fatigue, and reduced quality of life, and in some cases may lead to liver transplantation even without full liver failure.

The FDA approval is supported by results from the global GLISTEN Phase III trial, which successfully achieved its primary and key secondary endpoints. The study showed rapid improvement in itching as early as two weeks, with sustained benefits over 24 weeks, along with reduced sleep disturbance compared to placebo.

Linerixibat has also received Orphan Drug Designation in the United States, European Union, and Japan, along with priority review status in China for this indication. Regulatory submissions for the drug are currently under review in the EU, UK, Canada, and China.

ICOTYDE Secures FDA Approval, Advancing First-Line Systemic Treatment for Plaque Psoriasis

Johnson & Johnson has announced that the U.S. Food and Drug Administration (FDA) has approved ICOTYDE (icotrokinra), an interleukin-23 (IL-23) receptor antagonist, for treating moderate-to-severe plaque psoriasis. The therapy is indicated for adults and adolescents aged 12 years and older, weighing at least 40 kg, who are eligible for systemic therapy or phototherapy.

ICOTYDE is the first and only targeted oral peptide designed to selectively inhibit the IL-23 receptor. It successfully achieved all primary efficacy endpoints and demonstrated a strong safety profile across four Phase 3 trials involving around 2,500 patients.

The ICOTYDE approval is supported by extensive data from the ICONIC clinical development program, which evaluated the drug across both adult and adolescent populations, including difficult-to-treat areas such as the scalp and genital regions, as well as in head-to-head studies against an active comparator. In these superiority trials, nearly 70% of patients reached clear or almost clear skin (IGA 0/1), while 55% achieved a Psoriasis Area and Severity Index (PASI) 90 response by Week 16.

Adverse event rates in patients treated with ICOTYDE were comparable to placebo, with a difference of just 1.1% through Week 16, and no new safety concerns were observed up to Week 52.

Novartis Signs Deal to Acquire a Pan-mutant PI3Kα Inhibitor

Novartis has announced a deal with Synnovation Therapeutics, LLC to acquire SNV4818, a pan-mutant–selective PI3Kα inhibitor. This move reflects a next-generation strategy aimed at treating patients with HR+/HER2- breast cancer, with potential applications across other solid tumors.

SNV4818 is an orally administered therapy currently under investigation in a Phase 1/2 trial for breast cancer and advanced solid malignancies. The role of PI3Kα mutations in HR+/HER2- breast cancer is well established, with roughly 40% of patients experiencing poorer outcomes due to PIK3CA mutations. The program aligns with Novartis’ broader focus on improving outcomes in breast cancer and complements existing treatment approaches such as CDK inhibitors and endocrine (hormonal) therapies, potentially as part of combination regimens.

The drug is specifically engineered to target mutated PI3Kα in cancer cells while sparing the normal (wild-type) enzyme in healthy tissues. In contrast, currently available PI3Kα inhibitors affect both mutant and normal forms, often resulting in tolerability issues that limit long-term use. By selectively inhibiting the mutated enzyme, SNV4818 is intended to minimize adverse effects, enable more consistent dosing, and facilitate earlier use in combination with other therapies. Preclinical findings demonstrate strong activity against common PIK3CA mutations and high selectivity versus the normal enzyme, with clinical studies ongoing.