At the November 2024 meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisation under exceptional circumstances for InflaRx’s Gohibic® (vilobelimab) for treatment of adults with SARS-CoV2-induced acute respiratory distress syndrome (ARDS) who are receiving systemic corticosteroids.  A marketing authorisation under exceptional circumstances is recommended when the benefit/risk assessment is positive but where the rarity of the disease means it is unlikely that comprehensive data can be obtained under normal conditions of use.

The CHMP also recommended the following indication extensions:

• MSD’s Keytruda® (pembrolizumab), in combination with pemetrexed and platinum chemotherapy for first-line treatment of adults with unresectable non-epithelioid malignant pleural mesothelioma;
• BMS’ Opdivo® (nivolumab) and Yervoy® (ipilimumab), in combination, for mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer in first-line treatment of unresectable or metastatic colorectal cancer or for treatment of metastatic colorectal cancer after prior fluoropyrimidine-based combination chemotherapy;
• Janssen’s Rybrevant® (amivantamab), in combination with lazertinib, for first-line treatment of adult patients with advanced NSCLC with EGFR Exon 19 deletions or Exon 21 l858R substitution mutations;
• Sanofi’s Kevzara® (sarilumab), in a new strength (175mg/ml solution for injection in vial), for active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older, who have responded inadequately to previous therapy with conventional synthetic DMARDs, as monotherapy or in combination with MTX; and Sarclisa® (isatuximab), in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant;
• Regeneron/Ultragenyx’s Evkeeza® (evinacumab) as an adjunct to diet and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies for the treatment of adult and paediatric patients aged 6 months and older with homozygous familial hypercholesterolaemia.

Four biosimilars also received positive opinions at CHMP’s November meeting; two Samsung Bioepis denosumab biosimilars (reported here) and two aflibercept biosimilars for Formycon/Klinge (reported here).

In addition, the CHMP adopted a positive opinion for Eisai’s Leqembi® (lecanemab), as reported here.

On 15 November 2024, Sandoz announced that its Afqlir®, biosimilar to Bayer/Regeneron’s Eylea® (aflibercept), has been approved in Europe for the treatment of nAMD, macular oedema following retinal vein occlusion (RVO), diabetic macular oedema (DME) and myopic choroidal neovascularisation (mCNV).  Afqlir® obtained a positive recommendation from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) in September 2024.  Sandoz expects to launch in Europe in Q4 2025.

Sandoz’s news comes the same day of Formycon’s announcement that the CHMP has issued a positive opinion for its aflibercept biosimilar, FYB203/Baiama®/Ahzantive®, for the same indications as those of Afqlir®.  Klinge Biopharma holds the global commercialisation rights for FYB203 and is the marketing authorisation applicant for Ahzantive® in Europe (Formycon is the applicant for Baiama®).  The positive CHMP opinion follows the EMA’s acceptance of Formycon’s marketing authorisation application (MAA) for FYB203 in December 2023.  Formycon expects to receive marketing authorisation in the second half of January 2025.

Sandoz’s Afqlir® is the second aflibercept biosimilar to be approved in Europe, following the approval of Biocon’s Yesafili® in September 2023 (with UK approval following in November 2023).  Alvotech/Advanz Pharma’s MAA for AVT06 (aflibercept) was accepted by EMA in August 2024.  In July 2024, Altos Biologics announced that it submitted an MAA to the EMA for its aflibercept biosimilar ALT-L9, with marketing approval expected in 2025.  A positive CHMP opinion was adopted for Samsung Bioepis/Biogen’s Opuviz™ in September 2024.

There are currently five aflibercept biosimilars approved in the US: Sandoz’s Enzeevu™ (August 2024), Formycon/Klinge’s Ahzantive®/FYB203 (June 2024), Amgen’s Pavblu™ (August 2024), Biocon’s Yesafili™ (May 2024) and Samsung Bioepis’ Opuviz™/SB15 (May 2024).

On 15 November 2024, Regeneron and Sanofi announced that the US FDA has accepted for review their resubmitted supplemental Biologics Licence Application (sBLA) for Dupixent® (dupilumab) for patients aged 12 years and older with chronic spontaneous urticaria (CSU) whose disease is not adequately controlled with H1 antihistamine treatment.  The FDA’s target action date is 18 April 2025.

Regeneron and Sanofi had received a Complete Response Letter from the FDA in October 2023 requiring further efficacy data for the use of Dupixent® for CSU.

The resubmitted sBLA was supported by data from the LIBERTY-CUPID Phase 3 clinical program.  This included a confirmatory phase 3 study of Dupixent® which met the primary and key secondary endpoints for treatment of patients with uncontrolled, biologic-naïve CSU receiving background therapy with antihistamines.

Japan was the first country in the world to approve Dupixent® for CSU in February 2024.

In October 2024, Sanofi reported that sales of Dupixent® for Q3 2024 had increased globally by 24% to €3.5 billion and were expected to total about €13bn for the full year.

On 14 November 2024, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions for Samsung Bioepis’ Obodence™ (SB16/denosumab) and Xbryk™ (SB16/denosumab), biosimilars to Amgen’s Prolia® and Xgeva®, respectively.

Obodence™ is recommended for approval for the treatment of osteoporosis in postmenopausal women, bone loss linked to hormone ablation in men at increased risk of fractures, and bone loss associated with long-term treatment with systemic glucocorticoid therapy.

Xbryk™ is recommended for approval for the prevention of bone complications in adults with advanced cancer involving bone and for the treatment of adults and skeletally mature adolescents with giant cell tumour of bone.

Sandoz’s Jubbonti® and Wyost® were the first denosumab biosimilars to be approved in Europe in May 2024.  The EMA has accepted MAAs for denosumab biosimilars including for STADA/Alvotech (AVT03, October 2024), Teva (TVB-009P, October 2024), Gedeon Richter (July 2024), Fresenius Kabi (FKS518, July 2024), and Shanghai Henlius Biotech/Organon (HLX14, May 2024).

On 5 November 2024, the Australian Register of Therapeutic Goods (ARTG), approved 5 supplemental brands for Amgen’s denosumab (Ganvado™, Zerount™, Corora™, Rexadev™ and Deptargis™), none of which have been approved elsewhere to date.

On 14 November 2024, Sanofi announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of Sarclisa® (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT).  This follows approval of Sarclisa® for multiple myeloma by the US FDA in September 2024.

On 12 November 2024, FirstWord Pharma reported that Sanofi has succeeded in an appeal in the UK against the NICE’s June 2024 Final Draft Guidance recommending against Sarclisa® as a regimen alongside pomalidomide and dexamethasone for relapsed relapsed/refractory multiple myeloma (RRMM).  NICE has agreed to re-assess Sarclisa® at a third Committee Meeting.

This follows Sanofi’s announcement in September 2024 that the US FDA approved a new indication of Sarclisa® in combination with bortezomib, lenalidomide, and dexamethasone as a first line treatment option for adult patients with NDMM who are not eligible for autologous stem cell transplant.  Sarclisa® has previously been approved in over 50 countries (in combination with pomalidomide and dexamethasone) for treatment of RRMM in patients who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy.

On 14 November 2024, Eisai reported that it has received a positive opinion from the European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommending approval of Leqembi® (lecanemab) for use in treating patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (Early Alzheimer’s disease) who are apolipoprotein E ε4 non-carriers or heterozygotes with confirmed amyloid pathology.  The positive CHMP opinion follows Eisai’s request for re-examination of a prior negative opinion issued by the CHMP in July 2024.

Leqembi® has previously been approved for MCI and Early Alzheimer’s disease in the UK (August 2024), the US, Japan, China, South Korea, Hong Kong and Israel, and the UAE, and applications are under review in the Brazil, Canada, India, Russia, Taiwan, Singapore, and Switzerland.  In October 2024, Australia’s TGA decided against registering Leqembi® for these indications due to safety and efficacy concerns.

On 14 November 2024, Merck (known as MSD outside the US and Canada) announced that it has entered an exclusive global licence agreement with Shanghai-based LaNova Medicines Ltd to develop, manufacture and commercialise LM-299, LaNova’s investigational PD-1/VEGF bispecific antibody.

Under the agreement, MSD will make an upfront payment of US$588 million to LaNova, which is also eligible to receive up to US$2.7 billion in milestone payments.  The deal is expected to close in Q4 2024, subject to regulatory approvals.

In October 2024, MSD entered an agreement with ABL Bio for evaluation of ABL’s bispecific antibody ABL 103 in combination with MSD’s Keytruda® (pembrolizumab).  In August 2024, MSD and Curon Biopharmaceutical announced MSD’s acquisition of Curon-developed CD3xCD19 bispecific antibody CN201, currently in Ph I/II trials for the treatment of B-cell associated diseases.

On 14 November 2024, GlaxoSmithKline (GSK) announced positive results from a planned interim analysis of the DREAMM-7 head-to-head phase III trial evaluating Blenrep® (belantamab mafodotin) in combination with BorDex (bortezomib plus dexamethasone) as a second-line or later treatment for relapsed or refractory multiple myeloma (RRMM).  The results demonstrated that the Blenrep® combination treatment significantly reduced the risk of death versus standard of care daratumumab plus BorDex.  GSK plans to present the full results at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition on 9 December 2024.

Earlier interim data from the DREAMM-7 trial was reported in February 2024, showing a 59% further reduction in risk of disease progression or death, 23.2 more months of median progression-free survival, and a 43% reduction in risk of death.

This follows GSK’s announcement in September 2024 that Japan’s Ministry of Health accepted for review a new drug application for Blenrep® in combination with BorDex or PomDex (pomalidomide plus dexamethasone) as a treatment for RRMM.

On 14 November 2024, UCB announced the presentation of new two-year data from phase 3 studies of Bimzelx® (bimekizumab-bkzx) showing sustained improvements in clinical and patient-reported outcomes in adults with active psoriatic arthritis (PsA) and ankylosing spondylitis (AS).  The data demonstrated that, of responders who achieved at least 50% improvement from baseline response criteria for PsA, 75% maintained response to two years.  Of patients who achieved a 40% improvement in response criteria for AS, 85% maintained this response to two years.

This follows FDA approval of 2 mL pre-filled syringe and pre-filled autoinjector presentations in October 2024, each containing 320 mg of Bimzelx®, adding to the already approved 1 ml (160 mg) device presentation.  On 23 September 2024, UCB received FDA approval for three new indications of Bimzelx®, including active psoriatic arthritis, active non-radiographic axial spondyloarthritis with objective signs of inflammation and active ankylosing spondylitis.

GLP-1 agonists (also known as GLP-1 receptor agonists) represent a class of medications used to treat type 2 diabetes mellitus.  Well-known examples of drugs in this class include those manufactured by Novo Nordisk, such as liraglutide (marketed under Victoza® and Saxenda®) and semaglutide (marketed under Ozempic® and Wegovy®).  Semaglutide in particular has shown potential for addressing additional health concerns, such as weight loss, heart failure, kidney disease and liver health.  Two recent publications appear to further expand the potential for semaglutide to treat knee pain, and both semaglutide and liraglutide to treat alcohol use disorder.

A recent Novo Nordisk funded study, published in the New England Journal of Medicine on 30 October 2024, investigated semaglutide’s impact on knee pain in people with obesity and osteoarthritis.  Over 68 weeks, participants receiving semaglutide lost an average of 13% of their body weight, significantly more than the placebo group, and reported greater reductions in knee pain and improved knee function.  This effect may stem from weight loss reducing joint stress and possible anti-inflammatory properties of semaglutide, which might protect cartilage.

More recently, a new study published in JAMA Psychiatry on 13 November 2024, has shown that semaglutide and liraglutide may help reduce alcohol consumption in people with alcohol use disorder, particularly those with obesity or type 2 diabetes.  Analysing 17 years of data from over 220,000 individuals, researchers found those taking these GLP-1 receptor agonists had fewer alcohol-related hospitalisations than those using medications specifically for alcohol addiction treatment.  Specifically, only 5% of GLP-1 receptor agonist users were hospitalised for alcohol use issues, compared to 40% of those on traditional addiction-treating medications.  The study used data from the REWHARD consortium supported by the Swedish Research Council and one of the authors was funded by Sigrid Jusélius Foundation.

Both studies have pointed to the need for further trials to elucidate the underlying mechanisms for GLP-1 receptor agonist action in treatment.