mRNA-1010

Moderna has locked horns with US regulators over its standalone seasonal flu vaccine in recent days, but the company appears to be enjoying a more receptive regulatory environment in Europe. On Thursday, the European Medicines Agency's (EMA) drug advisory panel issued a positive opinion for mCombriax (mRNA-1083), making it the first combined mRNA vaccine designed to protect adults 50 years and older against both seasonal influenza and COVID-19.The shot targets SARS-CoV-2 and three influenza strains – A/H1N1, A/H3N2 and B/Victoria – using mRNA molecules that encode viral surface proteins.The Phase III study used to support the filing included over 8000 participants aged 50-plus, and showed that mCombriax generated antibody responses against influenza and SARS-CoV-2 that were statistically non-inferior to co-administration of authorised vaccines, including Moderna's Spikevax for COVID-19 and either Fluzone HD or Fluarix for influenza, marketed by Sanofi and GSK, respectively.The EMA panel also noted that a study of a similar mRNA vaccine containing only the influenza component in mCombriax showed it could prevent influenza illness and trigger an adequate immune response. The most common side effects included injection-site pain, fatigue and muscle pain, and typically resolved within a median three days.Moderna has been struggling more with regulators in the US, however. The company voluntarily withdrew its application for mRNA-1083 last year after the FDA requested additional Phase III influenza efficacy data. The biotech had planned to resubmit a filing for the combo vaccine once the review for mRNA-1010, its standalone mRNA vaccine for influenza, was under way.Those plans hit a snag a few weeks ago after the FDA issued a refuse-to-file (RTF) letter for mRNA-1010, saying the company had not used an appropriate comparator during clinical testing. Moderna called the decision "inconsistent" with prior FDA feedback. However, after meeting with the company, the US regulator agreed to review the filing after all, setting a target review date of August 5.

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.