On 20 December 2024, Australia’s Pharmaceutical Benefits Assessment Committee (PBAC) published the outcomes considered at its November 2024 meeting.

The following biosimilars were recommended for listing on the Pharmaceutical Benefits Scheme (PBS):

• Sandoz’s Wyost®, biosimilar to Amgen’s Prolia® and Xgeva® (denosumab), for osteoporosis, giant cell tumour of bone, and bone metastases
• Celltrion’s Steqeyma®, biosimilar to Janssen’s Stelara® (ustekinumab), for severe chronic plaque psoriasis, severe psoriatic arthritis, Crohn’s disease, complex refractory fistulising Crohn’s disease, and moderate to severe ulcerative colitis.

Among the originator biopharmaceuticals, Bayer secured a recommendation for its Eylea® (aflibercept) indication expansion for diabetic macular oedema and subfoveal choroidal neovascularisation secondary to age-related macular degeneration.  Novo Nordisk’s Ozempic® (semaglutide) also received a positive recommendation for type 2 diabetes mellitus, following its application for a new strength formulation.

Several oncology treatments received positive recommendations, including Janssen’s Rybrevant® (amivantamab) for non-small cell lung cancer.  Other cancer treatments recommended include Amgen’s Blincyto® (blinatumomab) for MRD-negative B-cell precursor acute lymphoblastic leukaemia, AstraZeneca’s combination therapy Imfinzi®/Lynparza® (durvalumab/olaparib) for advanced, metastatic or recurrent endometrial cancer, and Astellas Pharma’s Padcev® (enfortumab vedotin) for locally advanced or metastatic urothelial cancer.

AbbVie’s Epkinly® (epcoritamab) received a recommendation for relapsed or refractory diffuse large B-cell lymphoma, while Novartis’ Aimovig® (erenumab) was recommended for chronic migraine.

For hereditary angioedema, both CSL’s garadacimab and Takeda’s Takhzyro® (lanadelumab) secured positive recommendations.

Additional recommendations were granted to BMS’s Opdivo® (nivolumab) for urothelial carcinoma, MSD’s Keytruda® (pembrolizumab) for renal cell carcinoma, and Alexion Pharmaceuticals’ Ultomiris® (ravulizumab) for Neuromyelitis Optica Spectrum Disorder.

BeiGene’s Tevimbra® (tislelizumab) also received a positive recommendation for oesophageal squamous cell carcinoma.

The PBAC reports that some earlier recommendations have been extended:

• Sanofi’s Dupixent® (dupilumab) for chronic severe atopic dermatitis and uncontrolled severe asthma

Additionally, two recommendations have been rescinded:

• Celltrion Remsima SC® (infliximab) for rheumatoid arthritis
• AbbVie’s Skyrizi® (risankizumab) for Crohn’s disease

On 20 December 2024, Fresenius Kabi announced that it had entered into a licensing agreement with SamChunDang Pharm (SCD) to exclusively commercialise South Korean developed SCD-411, biosimilar to Regeneron’s Eylea® (aflibercept), in the United States, Brazil, Argentina, Chile, Paraguay, Colombia, and Mexico.  SCD is responsible for the development, manufacture, and supply of SCD-411.

This licensing deal follows news in March this year that SCD entered an exclusive distribution agreement with an unnamed distributor to supply SCD-411 in the UK, Belgium, the Netherlands, Norway, Portugal, Sweden, Greece, Ireland, and Finland.   SCD-411 was also the subject of an exclusive distribution agreement reported in November 2023, between SCD and an unnamed distributor, for supply to Austria, Germany, Italy, Spain, and Switzerland.  SCD has licensed SCD411 to Apotex for the Canadian market.

At its December 2024 meeting, the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions for six biosimilars.

Four of these are Celltrion biosimilars: Eydenzelt®/CT-P42 (aflibercept), biosimilar to Regeneron/Bayer’s Eylea®; Osenvelt®/CT-P41 (denosumab), biosimilar to Amgen’s Xgeva®; Stoboclo®/CT-P41 (denosumab), biosimilar to Amgen’s Prolia®; and Avtozma®/CT-P47 (tocilizumab), biosimilar to Roche’s Actemra®.

Biocon’s Yesintek® (ustekinumab), biosimilar to J&J’s Stelara® and CuraTeQ’s Zefylti® (filgrastim), biosimilar to Amgen’s Neupogen® were also given the green light by CHMP at its December 2024 meeting.

Eydenzelt® follows three aflibercept biosimilars already approved in the EU: Biocon’s Yesafili® (September 2023), Sandoz’s Afqlir® (November 2024) and Samsung Bioepis/Biogen’s Opuviz™ (SB15) (November 2024).  Formycon/Klinge’s FYB203/Baiama®/Ahzantive® received a CHMP positive opinion in November 2024.  Alvotech/Advanz Pharma and Altos Biologics have submitted MAA’s to the EMA for aflibercept biosimilars.

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).  In November 2024, CHMP adopted positive opinions for Samsung Bioepis’ Obodence™ and Xbryk™ (SB16).

The first tocilizumab biosimilar launched in Europe was Fresenius Kabi’s Tyenne®, in both IV and SC forms, in November 2023.  This was followed by the EU-approval of Biogen’s IV tocilizumab, Tofidence™, in June 2024.

Three ustekinumab biosimilars were launched during 2024, STADA/Alvotech’s Uzprovo® and Sandoz’s Pyzchiva® in July 2024, and Celltrion’s SteQeyma® in November 2024.  Previously approved ustekinumab biosimilars in Europe include Formycon/Fresenius’ Otulfi®/FYB202 (September 2024), Samsung Bioepis’ Eksunbi™ (September 2024) and Amgen’s Wezenla™ (June 2024).  Bio-Thera’s MAA for BAT2206 (ustekinumab) was also accepted by the EMA in July 2024.

On 2 December 2024, Formycon filed a petition for inter partes review of Regeneron’s US Patent No. 11,084,865 regarding ophthalmic formulations of aflibercept, such as Eylea®.  The petition closely followed a petition filed by Samsung Bioepis in relation to the same patent on 20 November 2024.  Both petitions challenge the 865 patent for obviousness.  Formycon has requested joinder of its petition with that of Samsung Bioepis.

Formycon/Klinge’s aflibercept biosimilar, Ahzantive®/FYB203, was approved in the US in June 2024.  Samsung Bioepis’ Opuviz™/SB15  received US approval in May 2024.  Other aflibercept biosimilars approved in the US are Sandoz’s Enzeevu™ (August 2024), Amgen’s Pavblu™ (August 2024) and Biocon’s Yesafili™ (May 2024).  Amgen’s Pavblu® was launched in the US in October 2024 following the Court of Appeals for the Federal Circuit’s denial of Regeneron’s application for an injunction against Amgen earlier in October 2024.

This patent is hotly contested in the US.  The US District Court for the Northern District of West Virginia recently granted preliminary injunctions against Samsung Bioepis (14 June 2024), Formycon (21 June 2024) and Celltrion (June-July 2024), and a permanent injunction against Biocon (11 June 2024), based on findings of infringement of the same patent (Regeneron’s US patent 11,084,865).  Samsung Bioepis, Formycon and Celltrion lodged appeals from the preliminary injunction orders (on 14 June 2024, 25 June 2024, and 10 July 2024, respectively).  Biocon filed a Notice of Appeal from the permanent injunction order on 21 June 2024.  Those appeals are all pending.

On 18 November 2024, Samsung Bioepis and Biogen announced that the European Commission has approved Opuviz™/SB15, biosimilar to Regeneron/Bayer’s Eylea® (aflibercept).  A positive CHMP opinion was adopted for Opuviz™ in September 2024.

Opuviz™ is approved for the treatment of nAMD and visual impairment due to: macular oedema secondary to retinal vein occlusion (RVO; branch or central RVO); diabetic macular oedema (DME), and myopic choroidal neovascularisation (CNV).

Samsung Bioepis and Biogen entered into a commercialisation agreement for Opuviz™ (SB15) in November 2019 for US, Canada, Europe, Japan and Australia.  The agreement also covers a second ophthalmology biosimilar, Byooviz™ (SB11, ranibizumab).

Opuviz™ is the third aflibercept biosimilar to be approved in the EU, closely following last week’s approval of Sandoz’s Afqlir®.  Biocon’s Yesafili® was approved in September 2023 (with UK approval following in November 2023).  Alvotech/Advanz Pharma’s MAA for AVT06 (aflibercept) was accepted by the 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.  Formycon/Klinge announced on 15 November 2024 that their aflibercept biosimilar FYB203/Baiama®/Ahzantive® received a positive opinion from the CHMP.

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 13 November 2024, Alvotech announced its financial results for the first 9 months of 2024, reporting an increase in total revenues of US $300 million and an over four-fold increase in product revenue, year on year.

Product development highlights for the year to date include the EMA acceptance of marketing authorisation applications for AVT03 (denosumab), biosimilar to Amgen’s Prolia® and Xgeva® in October 2024, and AVT05 (golimumab), biosimilar to Janssen’s Simponi®, in November 2024.  Alvotech has commercialisation agreements for European markets with STADA and Dr Reddy’s in relation to AVT03 and with Advanz Pharma in relation to AVT05.

In October 2024, the US FDA also approved a new presentation of Alvotech and Teva’s Selarsdi®/AVT04 (ustekinumab-aekn), biosimilar to Janssen’s Stelara®, in a 130 mg/26mL single-dose vial for IV infusion and a label expansion to include treatment for Crohn’s disease and ulcerative colitis.  Alvotech expects a February 2025 US launch for Selarsdi®.

A further highlight is said to be Alvotech’s commencement in September 2024 of a Phase 3 clinical trial for AVT16, biosimilar to Takeda’s Entyvio® (vedolizumab), in moderate to severe ulcerative colitis.

Alvotech reports licence and other revenue for the first 9 months of 2024 totalling US$210.5 million, primarily attributable to R&D milestones for the approval of AVT04/Uzpruvo® (ustekinumab) in Europe in January 2024, the commencement of the AVT16 (vedolizumab) clinical trials, European MAA submissions for AVT03 (denosumab) and AVT06 (aflibercept), and confirmatory efficacy and safety trials completed for AVT03 (denosumab) and AVT05 (golimumab).  There was also achievement of a performance milestone for the product launch of AVT04 (ustekinumab) in Japan (as Ustekinumab BS (F)) and Europe (as Uzpruvo®), a sales target for AVT02 (adalimumab) in Europe and Canada, and a product launch of AVT02 (as Simlandi®) in the US.

On 8 November 2024, Celltrion announced that it has achieved accumulated sales for Q3 2024 of KRW 2.4 trillion, surpassing its 2023 annual sales.  Its quarterly sales are the highest it has ever reported, up 31.2% year on year.

Celltrion attributes its sales growth to the expansion of global prescriptions for its subcutaneous infliximab, Remsima SC® (EU, launched in 2020)/Zymfentra™ (US, launched in March 2024), biosimilar adalimumab.  Yuflyma® (80mg dose US launch January 2024, 40mg dose first approved by the FDA in May 2023, launched 2023, paediatric form US launch March 2024), and biosimilar bevacizumab, Vegzelma® (US launch April 2023).  It has also experienced steady growth in its anticancer products, Truxima® (rituximab, US launch May 2020) and  Herzuma® (trastuzumab, US launch March 2020).

During 2024, Zymfentra™ secured all six public and private insurance contracts operated by the three major prescription drug managers (PBMs) in the US.  Celltrion estimates that it has now secured more than 90% coverage in the US insurance market by completing contracts with 30 mid- to large-sized and regional PBMs and insurance companies.

Celltrion also notes the expansion of its biosimilar portfolio during 2024 with the launch of SteQeyma® (ustekinumab) in major European countries on 1 November.  Celltrion is planning for the 2025 launch of Eydenzelt® (CT-P42, aflibercept).

Celltrion has a number of biosimilars under development, including CT-P41 (denosumab, US aBLA filed December 2023),  CT-P47 (tocilizumab), CT-P55 (secukinumab), CT-P53 (ocrelizumab) and CT-P51 (pembrolizumab).

On 30 October 2024, Sandoz announced its Q3 and 9-month 2024 financial results, reporting third quarter net sales of USD 2.6 billion, up 12% in constant currencies, year-on-year.  Net sales for the first 9 months of the year were USD 7.6 billion, an increase of 9% in constant currencies compared to the same period in 2023.

Sandoz experienced strong biosimilars growth of 37% (to USD 741 million) and 32% (to USD 2.1 billion) in constant currencies (YoY) for the quarter and the year to date respectively.  This is attributed to the European launches of Pyzchiva® (ustekinumab) in July 2024 and Tyruko® (natalizumab) in January 2024, the Canadian launch of Wyost®/Jubbonti® (denosumab) in August 2024, the acquisition of Cimerli® (ranibizumab) from Coherus announced in January 2024, the uptake of Hyrimoz® (adalimumab) in the US and the continued strong demand for Sandoz’s very first biosimilar Omnitrope® (somatropin).

Key biosimilar milestones for Q3/2024 are reported to include the FDA approvals of Enzeevu^TM (aflibercept) in August 2024 and Pyzchiva® (ustekinumab) in July 2024, and the launch of the first European biosimilar to Janssen’s Stelara®, Pyzchiva® (ustekinumab), in July 2024.  Sandoz intends to launch Pyzchiva® in the US in February 2025 in the first wave of biosimilars, while the US-launch of Enzeevu™ is dependent upon factors including the outcome of ongoing BPCIA litigation.