On 18 October 2024, Regeneron announced positive three year results for Eylea HD® (aflibercept, 8 mg injection) from an extension study of the Phase 3 PHOTON trial in patients with diabetic macular oedema (DME).  The results were presented at the American Academy of Ophthalmology (AAO) Annual Meeting.

The data reportedly demonstrates that the vast majority of Eylea HD® patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year and achieved longer treatment intervals.  Patients who switched to Eylea HD® reportedly experienced slower fluid re-accumulation following their first dose.  According to Regeneron, the longer dosing intervals and slower fluid re-accumulation supports the longer duration of action of Eylea HD®.

Eylea® 8mg was jointly developed by Bayer and Regeneron.  Regeneron holds the exclusive rights to both low and high dose Eylea® in the US, while Bayer holds those outside the US, where the companies equally share the profits from sales of the products.

High dose Eylea® for intravitreal injection has previously been approved for nAMD and DME in Australia (June 2024), the EU (January 2024), Japan (January 2024), and the UK (January 2024).  Eylea HD® was approved for nAMD, DME and diabetic retinopathy in the US (August 2023).

More recently, high dose Eylea® pre-filled syringe (OcuClick) was approved in Australia (October 2024) and Europe (September 2024).

On 18 October 2024, Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) published the outcomes of its September 2024 intracycle meeting.  This included consideration of proposals for broad Pharmaceutical Benefits Scheme (PBS) listings for PD-(L)1 inhibitors, including MSD’s pembrolizumab and BMS’ nivolumab, to allow expanded access to all current and future indications registered by the Therapeutic Goods Administration (TGA) without review of the clinical- and cost-effectiveness of each indication.  Consideration of these proposals had been deferred from the PBAC’s December 2023 meeting.

The PBAC determined that any broad subsidy proposal would need to address a list of parameters, including: “the potential risk of causing harm either directly (forgoing effective current standard treatments, adverse events) or intangibly (false hope, not resolving patient needs, inadequate provision of palliative care)”; the high level of uncertainty in cost-effectiveness when a PD-(L)1 inhibitor is not assessed for a specific listing based on clinical trial data for that use; the potential impact on other medicines (including PD-(L)1 inhibitors) that may already be in the market; and “biosimilar policies that might be in place, noting that multiple biosimilars for pembrolizumab and nivolumab are in the late phase of clinical development, with patents due to expire in some jurisdictions within the next five years”.  PBAC noted that, to date, it had not received an acceptable proposal for an expanded listing to facilitate broad access to PD-(L)1 inhibitors.

However, the PBAC said it is “supportive of implementing simplified listings for PD-(L)1 inhibitors within a specific tumour type if this would facilitate appropriate and timely access for patients”.  It is encouraging sponsors to make submissions for simplified PBS listings within tumour types “via the standard process”.

PD-(L)1 inhibitors currently listed on the PBS include MSD’s Keytruda® (pembrolizumab), BMS’ Opdivo® (nivolumab), AstraZeneca’s Imfinzi® (durvalumab), Merck Healthcare’s Bavencio® (avelumab), Medison Pharma Australia’s Libtayo® (cemiplimab) and GSK’s Jemperli® (dostarlimab).  BeiGene’s Tevimbra® (tislelizumab) and AA-Med’s toripalimab are under evaluation by the TGA.

On 18 October 2024, Astellas Pharma announced that the FDA has approved Vyloy™ (zolbetuximab-clzb) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours are claudin (CLDN) 18.2 positive.  Vyloy™ is the first CLDN18.2-targeted therapy approved in the U.S.

The US approval follows September 2024 approvals for the same Vyloy™ combination in Europe and Korea.  Vyloy™ has previously been approved in the UK (August 2024), Japan (March 2024) and China (August 2023).

At its October 2024 meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorisation for Novo Nordisk’s Alhemo® (concizumab) for routine prophylaxis of bleeding in patients of 12 years of age or more with haemophilia A (with FVIII inhibitors) or haemophilia B (with FIX inhibitors), and Lindis Biotech’s Korjuny® (catumaxomab) for malignant ascites.

The committee also recommended extensions of indications for Sanofi’s Kevzara® (sarilumab) for the treatment of polymyalgia rheumatica (PMR) in adult patients who have had an inadequate response to corticosteroids or who experience a relapse during corticosteroid taper, and BeiGene’s Tevimbra® (tislelizumab) for certain patients with previously untreated oesophageal squamous cell carcinoma (OSCC) and certain patients with gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

Two ustekinumab biosimilars also received positive opinions at CHMP’s October 2024 meeting, as reported here.

On 17 October 2024, Fresenius Kabi announced its Canadian launch of Tyenne®, biosimilar to Roche’s Actemra® (tocilizumab), in both IV and subcutaneous formulations. Tyenne® is indicated for the treatment of several inflammatory and immune diseases, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.  It is the first and only tocilizumab biosimilar to be launched to date in Canada.

Fresenius Kabi launched Tyenne® in Europe as the first to market biosimilar in November 2023 in both IV and subcutaneous formulations. Tyenne® was launched in the US in an IV formulation in April 2024 and in a subcutaneous formulation in July 2024.

At its October meeting, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions for Accord HealthCare’s, Imuldosa® (DMB-3115) and Absimky® (DMB-3115), biosimilars to Janssen’s Stelara® (ustekinumab).  Both biosimilars are indicated for plaque psoriasis, paediatric plaque psoriasis, psoriatic arthritis (PsA) and Crohn’s disease, with Absimky® additionally being indicated for ulcerative colitis.

In July 2021, Dong-A ST and Meiji Seika Pharma entered into an exclusive global licence agreement with Intas Pharmaceuticals, under which Intas received worldwide commercialisation rights for DMB-3115, excluding Korea, Japan and certain other Asian countries.  Intas is commercialising DMB-3115 via its subsidiaries, Accord Healthcare in the EU, UK and Canada, and Accord Biopharma in the US.

Earlier this month, Imuldosa® was approved by the FDA as the fifth approved ustekinumab biosimilar in the US.  Accord Biopharma reached a settlement with Janssen in October 2023, allowing DMB-3115 to launch in the US no later than 15 May 2025.

Previously approved ustekinumab biosimilars in Europe include Formycon/Fresenius’ Otulfi®/FYB202 (September 2024), Samsung Bioepis’ Eksunbi™ (September 2024), Celltrion’s SteQeyma®/CT-P47 (August 2024), Amgen’s Wezenla™ (June 2024), Sandoz/Samsung Bioepis’ Pyzchiva®/SB17 (April 2024, launched July 2024) and Alvotech/Stada’s Uzpruvo® (January 2024, launched July 2024).  Bio-Thera’s MAA for BAT2206 (ustekinumab) was accepted by the EMA in July 2024.

On 16 October 2024, Australia’s Therapeutic Goods Administration (TGA) reported its decision not to register Leqembi® (lecanemab) for the treatment of patients with mild Alzheimer’s dementia (early Alzheimer’s disease) and mild cognitive impairment (MCI) due to Alzheimer’s disease.  The decision is based on the TGA’s opinion that demonstrated efficacy did not outweigh the safety risks associated with use of lecanemab.  Dementia Australia has issued a media statement calling the decision a ‘blow’ for Australians living with Alzheimer’s disease.

Eisai Australia has advised the TGA that it intends to request reconsideration of the decision.

Leqembi® has previously been approved for MCI and mild dementia due to Alzheimer’s disease in the UK, US, Japan, China, South Korea, Hong Kong and Israel, and the UAE, and applications are under review in the European Union, Brazil, Canada, India, Russia, Taiwan, Singapore, Saudi Arabia and Switzerland.

In a draft guidance issued on 22 August 2024, the UK’s National Institute for Health and Care Excellence (NICE) found that the benefits of lecanemab were too small to warrant making the drug available on the NHS.

On 16 October 2024, Formycon announced that results of a comparative analytical evaluation of its FYB206, published in Drugs in R&D, showed FYB206 to be structurally and functionally “highly similar” to MSD’s Keytruda® (pembrolizumab).

FYB206 is currently being evaluated in a phase 1 trial (“Dahlia”) to compare the pharmacokinetics, safety and tolerability of FYB206 with Keytruda® in malignant melanoma (commenced June 2024) and a phase 3 trial (“Lotus”) to compare the efficacy and safety of FYB206 with Keytruda® in combination with chemotherapy in patients with non-small cell lung cancer (NSCLC) (commenced 30 July 2024).

A number of pembrolizumab biosimilars have entered clinical trials this year, including Celltrion’s CT-P51 (Ph 3 trial plan approved by FDA in August 2024), Bio-Thera’s BAT3306 (Ph 1/3 in nsNSCLC commenced 25 July 2024), Amgen’s ABP 234 (Ph 3 in nsNSCLC initiated May 2024), Samsung Bioepis’ SB27 (Ph 3 in metastatic nsNSCLC commenced April 2024) and Sandoz’s GME751 (Ph 1 and 3 commenced in April/May 2024).  In September 2024, Shanghai Henlius Biotech received approval in China for a clinical trial of its pembrolizumab biosimilar, HLX17.

On 16 October 2024, the Economic Times reported that the Delhi High Court has reinstated an injunction preventing Zydus from manufacturing, selling or marketing Sigrima™, biosimilar to Roche’s Perjeta® (pertuzumab).

The 16 October 2024 decision of the Delhi High Court follows an appeal by Roche of an earlier order of the Court on 9 October 2024, which reversed an injunction order originally granted in July 2024.

The injunction was ordered in proceedings commenced by Roche earlier this year, in which Roche alleges that Zydus’ Sigrima™ infringes Indian patent numbers IN 268632 and IN 464646. Zydus received conditional approval for its pertuzumab biosimilar from the Central Drug Standard Control Organisation (CDSCO) on 4 April 2024, obtained permission to market the drug on 27 June 2024 and subsequently launched Sigrima™ on the Indian market.

On 28 June 2024, Zydus and Dr Reddy’s announced that they had entered a licensing agreement to co-market Zydus’ pertuzumab biosimilar in India as Sigrima™ (Zydus) and Womab® (Dr Reddy’s).

On 16 October 2024, Chinese insulin maker Gan & Lee Pharmaceuticals reported its development of an injectable GLP-1 agonist, GZR18, which it claims has outperformed Novo Nordisk’s Ozempic® (semaglutide) in reducing glycated haemoglobin (HbA1c) and body weight in a phase 2 trial for patients with type 2 diabetes.  In the 24-week trial involving 264 patients, biweekly doses of GZR18 reportedly led to a greater HbA1c reduction (up to 2.32%) compared to semaglutide (1.60%) and a maximum weight loss of nearly 12 pounds, versus just over seven pounds for semaglutide.

Gan & Lee Pharmaceuticals also announced positive results for two insulin analogues, GZR4 and GZR101, in type 2 diabetes trials, both reportedly outperforming Novo Nordisk’s Tresiba® (insulin degludec) and Ryzodeg® (insulin degludec/insulin aspart), respectively.  In patients with poor glycaemic control, once-weekly GZR4 lowered HbA1c by 1.5%, slightly better than degludec’s 1.48%.  In another trial, GZR101 lowered HbA1c by 1.56%, which was greater than Ryzodeg’s 1.31%.