Iloperidone

After Europe's CHMP signed off on Moderna's combination COVID-19 and flu vaccine, CEO Stéphane Bancel praised the "EMA’s rigorous scientific review." While the FDA has flip-flopped on whether to review Moderna’s combination influenza and COVID-19 vaccine, it’s full speed ahead for the mRNA shot in Europe.The Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization to mCombriax for people aged 50 and older. The committee's thumbs up is the first for a combo vaccine that protects against the two respiratory infections. Earlier this month, the FDA sent a refusal-to-file (RTF) letter to Moderna, explaining that the comparator arm of the successful trial backing the submission did not “reflect the best-available standard of care.” Eight days later, after meeting with Moderna, the U.S. regulator accepted the company’s application and established an Aug. 5 action date for its decision on whether to approve the shot. The hesitance of the FDA and the quick sign off from the European Medicines Agency (EMA) highlights the differing regulatory environments vaccine makers are facing in their two largest markets. The regulators were largely aligned until the installation last year of vaccine skeptic Robert F. Kennedy Jr. as the chief of Health and Human Services (HHS).“We appreciate the EMA’s rigorous scientific review,” Moderna CEO Stéphane Bancel said in a release on Friday.It’s a much-needed win for Moderna, which has slumped since its overwhelming success with mRNA vaccine Spikevax, which generated $37 billion in revenue for the company in 2021 and 2022. “The CHMP’s positive opinion represents an important milestone for respiratory virus vaccination and for Moderna, with the introduction of the world’s first flu plus COVID combination vaccine,” Bancel added. “If approved, this would be Moderna’s fourth marketed product in Europe.”  In addition to the growing anti-vaccine sentiment in the U.S.—much of it fueled by misinformation—there is particular distrust from regulators in the U.S. about mRNA products, despite evidence of their safety.In making its decision, the CHMP cited World Health Organization data, which showed there have been more than 281 million cases of COVID-19 reported in Europe up until Feb. 1 of this year. Additionally, there are up to 50 million cases of seasonal flu each year in Europe. Sleeping sickness nod The CHMP has also recommended Acoziborole Winthrop as a treatment for gambiense sleeping sickness, a parasitic disease which is transmitted by the bite of an infected tsetse fly and has killed millions in central and west Africa over the past century. The medicine was co-developed by Sanofi and the Drugs for Neglected Diseases initiative (DNDi).The single-dose oral treatment would provide a significant advance over current therapies, which require either a 10-day course of oral medicine or a combination of injections and oral therapy for advanced cases. The recommendation applies to early and advanced-stage gambiense in those ages 12 and older.“In just 20 years, we have gone from complicated treatments including arsenic derivatives with serious side effects, to today, when a single-dose, one-day therapy could safely cure patients,” Luis Pizarro, M.D., the executive director of DNDi, said in a release. “This progress is [a] testament to the transformative power of collaborative science.” Two CHMP recommendations for hives condition Meanwhile, Novartis has secured a positive opinion from the CHMP on remibrutinib as an oral treatment for adults with chronic spontaneous urticaria (CSU) who have an inadequate response to antihistamines. In September of last year, the FDA approved the Bruton’s tyrosine kinase inhibitor (BTKi) treatment for the same indication, also known as chronic hives. The medicine’s commercial moniker in the U.S. is Rhapsido.“The introduction of remibrutinib represents a major advancement … with improvements in symptoms observed as early as Week 1,” Martin Metz, M.D., of the Institute of Allergology, Charité Universitätsmedizin in Berlin, said in a release.Sanofi also gained a CHMP positive opinion for its Regeneron-partnered blockbuster, Dupixent, as a treatment for children ages two through 11 years with CSU. This is the first biologic treatment for those under age 12 with the disorder. The FDA, which approved Dupixent for CSU in April of last year, has an April decision date on whether to expand its use to those ages of two through 11.Earlier this week, the FDA signed off on Dupixent in its ninth indication, allergic fungal rhinosinusitis (AFRS). Other CHMP recommendations Ipsen has scored a CHMP positive recommendation for its Day One Biopharmaceuticals-partnered Ojemda (tovorafenib) for patients six months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG), a type of cancerous brain tumor.The FDA endorsed Ojemda, a once-weekly oral therapy, in 2024. It competes with Novartis’ Tafinlar-Mekinist combo, which has a narrower label. The treatments provide an option to surgery and chemotherapy.Also scoring a CHMP nod is Mitsubishi Tanabe’s Onerji, a subcutaneous infusion of liquid levodopa and carbidopa, for adults with Parkinson’s disease. In 2015, AbbVie gained FDA approval for the combination treatment, known commercially as Duopa. The Japanese company gained Onerji in a $1.1-billion acquisition of NeuroDerm in 2017.  Crinetics has won a CHMP endorsement for Palsonify for the treatment of acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults and is caused by the pituitary gland producing excess growth hormone. The FDA signed off on the selectively targeted somatostatin receptor type 2 agonist in September of last year.Also making the grade with the CHMP is X4 Pharmaceuticals’ Xolremdi for WHIM syndrome, an ultra-rare hereditary condition in which the immune system does not work properly, making patients more susceptible to bacterial and viral infections. The FDA approved the first-of-its-kind treatment in 2024. 2 CHMP rejections Vanda Pharmaceuticals has been on a roll, gaining FDA approvals for two new drugs in the last two months. But the Washington, D.C.-based drugmaker has failed to make the grade with its atypical antipsychotic drug iloperidone. The CHMP has questioned its efficacy and safety, citing that iloperidone can cause a change in the heart’s electrical activity, which can lead to a “life-threatening heart rhythm abnormality.” The risk of using iloperidone outweighs the benefits of treatment, the CHMP said.Vanda was seeking approval for iloperidone as a treatment for schizophrenia and bipolar I disorder. It has been on the market in the U.S. as Fanapt since 2009. The CHMP also swatted back Acadia Pharmaceuticals’ Rett syndrome drug Daybu, questioning its efficacy. The FDA approved the treatment in 2023.

The EMA's drug advisory panel issued its latest basket of recommendations and rejections on Friday, throwing its support behind six drugs, whilst declining to back two treatments. The most notable nod went to Moderna for mCombriax (mRNA-1083), a combination mRNA vaccine designed to protect adults 50 years and older against both seasonal flu and COVID-19. The shot's support from European regulators comes shortly after the FDA initially declined to review a US application for the standalone flu portion of the jab — mRNA-1010 — before reversing course and promising a decision by August 5. With the positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) in-hand, Moderna is now awaiting a final marketing authorisation decision on mCombriax from the European Commission. Good news for Crinetics, NovartisJust five months after Crinetics Pharmaceuticals won US clearance for its once-daily oral acromegaly treatment, it now has CHMP backing for Palsonify (paltusotine) in the EU.The nonpeptide somatostatin receptor type 2 (SST2) agonist is supported by data from two Phase III pivotal trials, PATHFNDR-1 and PATHFNDR-2, which respectively enrolled previously treated and treatment-naïve adults with acromegaly, a rare hormonal disorder caused by the the production of excess growth hormone. In both studies, a significantly higher proportion of participants receiving Palsonify maintained IGF-1 levels ≤1 times the upper limit of normal compared with those on placebo, alongside significant reductions in acromegaly-associated symptoms.A FirstWord analysis pegged Crinetics as a likely takeout target this year, given its positive US launch of Palsonify (see – Vital Signs: The seller's marketplace heading into JPM).On a similar timeline as Crinetics, Novartis also bagged CHMP backing after a September FDA approval; the Swiss pharma got a positive recommendation for Rhapsido (remibrutinib) to treat chronic spontaneous urticaria (CSU).In the late-stage REMIX-1 and REMIX-2 studies, Rhapsido outperformed placebo on standard measures of itch, hive counts and overall disease activity at 12 weeks, with significantly more treated patients than placebo recipients reporting control of symptoms as early as the second week.In the US, the BTK inhibitor is indicated for adults who remain symptomatic despite taking antihistamines. As a twice-daily pill, it offers patients with CSU an oral alternative to existing injectable therapies.Nods for Ipsen, X4Also earning a thumbs up from CHMP was Ipsen and its paediatric brain cancer treatment, Ojemda (tovorafenib). The conditional marketing recommendation covers its use as monotherapy in patients aged 6 months and older with low-grade glioma harbouring a BRAF fusion or rearrangement or BRAF V600 mutation and who have progressed after one or more prior systemic therapies. Ipsen licensed the pan-RAF kinase inhibitor from Day One Biopharmaceuticals in 2024, after it received FDA approval in a similar setting. Rounding out the positive opinions was X4 Pharmaceuticals' Xolremdi (mavorixafor), which got a nod from CHMP "under exceptional circumstances" to treat patients aged 12 and up with WHIM syndrome, an ultra-rare immunodeficiency and chronic neutropenic disorder caused by CXCR4 pathway dysfunction; The disease is named for its four classic manifestations: warts, hypogammaglobulinaemia, infections and myelokathexis.Despite winning FDA approval in 2024 for the CXCR4 antagonist, X4 has struggled to remain afloat. The company in 2025 underwent two separate rounds of layoffs to stretch its cash runway to a topline readout of the Phase III 4WARD study evaluating Xolremdi in chronic neutropenia, expected next half. Negative opinions for Acadia, VandaOne of Friday's two rejections was not a surprise. Acadia Pharmaceuticals disclosed earlier this month that it expected to receive a negative opinion for trofinetide in Rett syndrome, a rare neurodevelopmental condition. Acadia has said it will seek a re-examination of its application for the IGF-1 analogue, which is already approved in the US and Canada under the brand name Daybue.The other thumbs-down, however, went to an atypical antipsychotic that has been cleared in the US to treat schizophrenia since 2009. More recently, Vanda Pharmaceutical's Fanapt (iloperidone) got a nod from the FDA in 2024 for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. In its rejection of iloperidone in both disease settings, CHMP wrote that the drug was associated with pronounced QT prolongation, "which is not outweighed by the benefits of treatment." Vanda may ask for re-examination of the opinion within 15 days.