Biosimilars are developed to be highly similar versions of approved biologics in terms of safety, purity, and potency. Biosimilars are expected to be a cost-effective alternative to high-priced branded biologics, offering significant and much-needed cost savings to both payers and patients. Hence physicians are likely to adopt biosimilars 'a reference product to biologics' possessing similar therapeutic properties. Alvotech seems to be keenly focusing on the commercialization of biosimilars in collaboration with Yas Holding and Stada. Pfizer also showed efforts in receiving the US FDA approval for its adalimumab biosimilar, Abrilada for RA. As well as the month of November was more over-focused on pegfilgrastim biosimilars. Our team at PharmaShots has summarized 16 key events of the biosimilar space of November 2019.

1.  Yas Holding Acquired Stake in Alvotech and Signs an Exclusive Agreement for its Three Biosimilar Candidates

Date - Nov 04, 2019

Product - Biosimilars

• Alvotech to receive ~$45M as up front, equity investment, milestone while Yas Holding acquired a 2.5% stake in Alvotech business and received rights to commercialize Alvotech's three biosimilar candidates in MENA region
• The investment complemented Yas holding's existing portfolio and expanded its footprints in health & pharmaceutical sector both in the MENA region and abroad
• Additionally, in Nov'2018, Fuji Pharma invested ~$50M for a 4.2% stake in the Alvotech and in Feb'2019 Fuji Pharma got exclusive rights to commercialize its biosimilar ustekinumab (referencing Stelara) in Japan

2. Sandoz's Ziextenzo (biosimilar, pegfilgrastim) Received the US FDA's Approval to Decrease the Incidence of Febrile Neutropenia

Date - Nov 05, 2019

Product - Ziextenzo (biosimilar, pegfilgrastim)

• The FDA's approval was based on three-way PK/PD study (LA-EP06-104) assessing Ziextenzo vs Neulasta (US), Ziextenzo vs Neulasta (EU), and Neulasta (US) vs Neulasta (EU) reference pegfilgrastim demonstrating no differences regarding safety and immunogenicity
• The addition of long-acting supportive oncology biosimilar expanded Sandoz's oncology portfolio. Following the approval, Sandoz is the first and only company offering physicians long- and short-acting filgrastim biosimilar treatment options in the US
• Ziextenzo (pegfilgrastim-bmez) is a long-acting form of filgrastim, indicated to reduce the incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer therapies and has been approved & marketed in the EU since 2018

3. Coherus Signed an Exclusive License Agreement with Bioeq for Biosimilar of Lucentis (ranibizumab) in the US

Date - Nov 06, 2019

Product - Lucentis (ranibizumab)

• Bioeq received up front, regulatory and launch milestones with equal profit sharing. Coherus to get exclusive rights to commercialize biosimilar candidate referencing Genentech's Lucentis with its anticipated launch in 2021 in the US
• Bioeq holds the responsibility for product delivery to the Coherus and submitted BLA to the US FDA in Q4'19
• The biosimilar of Lucentis, being evaluated in P-III study for wet age-related macular degeneration demonstrated bio similarity with the reference product. Bioeq will partner with other companies for its biosimilar ranibizumab ex-US by 2020

4. Biogen Signed an Exclusive Commercialization Agreement with Samsung Bioepis to Expand its Biosimilars Portfolio

Date - Nov 06, 2019

Product - Biosimilars

• Samsung Bioepis received $100M up front, up to $210M development, regulatory and commercial milestones. Biogen got exclusive commercialization rights for two ophthalmology biosimilars, SB11 referencing Lucentis and SB15 referencing Eylea in the US, Canada, EU, Japan, and Australia
• Additionally, Biogen received exclusive rights to commercialize anti-TNF portfolio including Benepali (etanercept), Flixabi (infliximab) & Imraldi (adalimumab) in exchange for royalties on sales in China and acquires an option for extending its existing commercial agreement with Samsung Bioepis for anti-TNF portfolio in EU
• The transaction is expected to be closed in Q4'19. Benapali, Flixabi & Imraldi are the biosimilars referencing Enbrel, Remicade & Humira indicated to treat RA, PsA, axSpA, and other autoimmune diseases respectively

5. Teva and Celltrion Reported the Availability of Truxima (biosimilar, rituximab) in the US

Date - Nov 07, 2019  

Product - Truxima (biosimilar, rituximab)

• Teva and Celltrion launched Truxima (rituximab-abbs) inj. as the first biosimilar referencing Roche's Rituxan (rituximab) to address unmet needs in the US by the week of November 11
• The approval of Truxima was based on clinical/ nonclinical, pharmacology, immunogenicity, clinical efficacy and safety data. Truxima was made available via primary wholesalers at a WAC of $845.55 for 100mg vial and $4227.75 for 500mg vial with its actual cost to be lower than WAC
• Truxima is the first rituximab biosimilar and has received FDA's approval to match all the reference product's oncology indications for NHL and CLL in May'2019. Additionally, Celltrion and Teva have a pending submission of Truxima for RA, GPA, & MPA with a license to expand its label to include these indications in Q2'20

6. Bio Thera's QLETLI (biosimilar, adalimumab) Received NMPA's Approval for Auto-Immune Diseases in China

Date - Nov 07, 2019

Products - QLETLI (biosimilar, adalimumab), Humira (adalimumab)

• The approval of QLETLI was based on P-III study resulted in meeting its 1EPs, demonstrating bio-similarity to the reference product, Humira (adalimumab) including clinical/nonclinical, PK/PD data
• The approval of QLETLI marked the first approval in a regulated market from Bio Thera's biosimilar portfolio and the second biosimilar to be approved by NMPA
• QLETLI (BAT1406) is an anti-TNF- a mAb, available as a prefilled syringe for SC injection, indicated for all indications including RA, AS, and plaque psoriasis of the reference product, Humira in China

7. STADA Signed an Exclusive Commercialization Agreement with Alvotech for Seven Biosimilars in Europe

Date - Nov 07, 2019

Product - Humira (adalimumab)

• Alvotech received up front with subsequent milestones for the next five years. STADA to get exclusive right to commercialize seven biosimilars in all key European markets and selected ex-EU markets
• Alvotech will remain responsible for the development, registration, and supply of the biosimilars within the EU. The collaboration will expand Alvotech's biosimilar portfolio and strengthen its presence in the EU
• The seven biosimilar products focused on treating autoimmunity, oncology and inflammatory diseases and ophthalmology for patients across the globe and generated $50M in sales globally

8. Samsung Bioepis Reported FDA's Acceptance of BLA for SB8 (biosimilar, bevacizumab)

Date - Nov 15, 2019

Product - SB8 (biosimilar, bevacizumab)

• The US FDA accepted the BLA for review under the 351(k)pathway for its biosimilar candidate, SB8 referencing Avastin (bevacizumab) which was submitted in Sept'2019
• Following the US FDA's approval, Merck will commercialize Samsung Bioepis SB8 in the US
• SB8 is a biosimilar referencing Roche's Avastin, designed to treat patients with advanced non-squamous non-small cell lung cancer. With the approval, Samsung Bioepis intends to enhance its biosimilar portfolio targeting immunology, oncology, ophthalmology, and hematology

9. NeuClone Reported Dosing of NeuLara (proposed biosimilar, ustekinumab) in P-I Trial

Date - Nov 17, 2019

Product - NeuLara (proposed biosimilar, ustekinumab)

• Australian Therapeutic Goods Administration (TGA) Clinical Trial Notification (CTN) scheme was responsible for conducting the NeuLara P-I trial and was conducted across 200 healthy volunteers assessing PK and safety of US- and EU-sourced Stelara
• NeuClone's NeuLara became the second biosimilar in pipeline to enter in clinical development and was developed in partnership with Serum Institute of India
• NeuLara is a mAb targeting IL-12 and IL-23 developed to treat patients with PSO, PsA, CD, and UC

10. Pfizer's Abrilada (biosimilar, adalimumab) Received the US FDA's Approval for Rheumatoid Arthritis

Date - Nov 18, 2019

Products - Abrilada (biosimilar, adalimumab), Humira (adalimumab)

• The US FDA approval was based on the clinical study assessing Abrilada (adalimumab-afzb) vs reference product, AbbVie’s Humira in 597 biologic-naïve patients with RA for 78 wks.
• Result: @26wks. patients achieved ACR20 (68.7% vs 72.7%) with a treatment difference of -3.98%, ACR20, 50, and 70 rates were similar with both groups
• The approval of Abrilada, a biosimilar to Humira fostered the biologics competition in the US with marked 9th biosimilar product in 2019, bringing the overall total of biosimilar approvals to 25

11. Biocon Reported the US FDA's Approval of sBLA for Fulphila (biosimilar, pegfilgrastim) Manufactured at its New Facility in Bengaluru

Date - Nov 27, 2019

Product - Fulphila (biosimilar, pegfilgrastim)

• The approval of the new manufacturing facility for Fulphila (biosimilar, pegfilgrastim) allowed Biocon and Mylan to expand their scale-up capacity, which access patients globally. The US FDA conducted a pre-approval inspection of the new manufacturing facility from Sep 10-19, 2019
• Biocon investigated in building global-scale, cost-competitive, complex manufacturing facilities addressing the global market opportunities. The approval met the patient needs for Fulphila across the globe
• Fulphila is a biosimilar referencing Neulasta, co-developed by Biocon and Mylan and is an approved therapy to reduce the duration of febrile neutropenia in multiple countries including the US, EU, Australia, and Canada

12. Qilu Reported Initiation of P-III Trial for QL1206 (biosimilar, denosumab) in China

Date - Nov 22, 2019  

Product - QL1206 (biosimilar, denosumab)

• The P-III trial involved assessing QL1206 (60 mg, SC) vs PBO (SC) in 216 patients every 6 months for 1 year. Additionally, the candidates will receive 500 mg of calcium and 1,000 IU of vitamin D daily
• The 1EP is to evaluate the effect of QL1206 and the 2EP is regarding safety, efficacy, immunogenicity, PK & PD including the objective to evaluate the effect of anti-drug antibodies (ADA) and AEs. The trial is expected to be completed in Jul' 2021  
• QL1206 has been currently evaluated in P-I trial assessing its PK, PD, safety in comparison with Xgeva enrolling 168 patients with its expected completion in May'2019

13. The US FDA Draft New Guidelines for Proposed Biosimilars and Interchangeable Insulins

Date - Nov 25, 2019 

Products - Biosimilar, Insulins

• The objective of this guideline is to provide recommendations on when and whether a comparison clinical immunogenicity study is required for biosimilar and interchangeable insulin products targeted to treat T-1 or T-2 diabetes mellitus
• The US FDA stated that if an analytical study is based on state-of-the-art technology supporting 'highly similar' for a biosimilar or interchangeable insulin then no clinical immunogenicity study will be required demonstrating minimal or no risk of clinical impact from immunogenicity. Additionally, include cases where immunogenicity study is required for products that show differences in certain impurities or novel excipients
• The FDA expects BLAs for biosimilar and interchangeable insulins include adequate chemistry, manufacturing, control information, a comprehensive comparative analytical assessment, a comparative clinical pharmacology study, and an immunogenicity assessment
• The guidelines will be implemented from Mar'2020 which includes the approved NDAs for insulins will be 'deemed to be licenses' under section 351(a) of the PHS Act referring to biologics and can be further used as reference products under section 351(k) of the PHS Act

14. Lupin Planned to Launch Two of its Biosimilars in the US

Date - Nov 29, 2019 

Products - Etanercept Biosimilar, Pegfilgrastim Biosimilars

• Lupin planned for EU approval of etanercept biosimilar in Mar'2020 with expected launch in Jul'2020 in European markets, has received approval in Japan in Mar'2019. Lupin also plans to file the approval of etanercept and pegfilgrastim biosimilars in the US in Q4 of the same year
• Etanercept is a mAb targeting inflammatory cytokine TNF and can be used to treat various forms of arthritis
• Additionally, Lupin has also signed an agreement with Mylan to launch its drug in Asia, Australia, EU, and New Zealand

15. Celltrion's Remsima SC (biosimilar, infliximab) Received EC's Approval for Rheumatoid Arthritis

Date - Nov 27, 2019

Product - Remsima (biosimilar, infliximab)

• The approval was based on P-I/III study assessing PK, efficacy, and safety of Remsima/CT-P13 SC + MTX vs CT-P13 IV in patients with active RA with inadequate response to DMARDs & demonstrated that switching patients from Remsima IV to its SC formulation @30wks. is comparable to maintaining Remsima SC up to 54wks.
• The approval provides patients an opportunity of self-administration to control their own treatment. Remsima SC develops fewer anti-drug antibodies leading to an improvement in treatment for patients with RA
• Remsima SC is the world's first SC formulation of infliximab and has received CHMP's positive opinion with its submission of MAA to EMA for extending its indication to IBD, a decision expected in mid-2020. Celltrion plans to launch Remsima SC across EU in Q1'20

16. Mochida Launched Teriparatide Biosimilar for the Treatment of Osteoporosis in Japan

Date - Nov 28, 2019

Product - Teriparatide

• Mochida launched 'Teriparatide BS SC injection Kit 600µg MOCHIDA' as it has been listed on the NIH reimbursement price list
• The launch will improve QoL and lead to the reduction of the financial burden of patients with osteoporosis. The teriparatide biosimilar has developed in collaboration with Gedeon Richter
• Teriparatide BS injection Kit 600µg is a novel biosimilar approved in Japan targeted for osteoporosis 20 µg SC recommended dose once a day for enhancing bone formation and improving bone structure. It is a disposable kit preparation with the delivery device and available for self-injection