FDA Approves PYZCHIVA® (ustekinumab-ttwe), Samsung Bioepis’ Biosimilar to Stelara

• PYZCHIVA becomes Samsung Bioepis’ seventh biosimilar and fourth immunology biosimilar approved by the FDA
• PYZCHIVA’s licensing period will begin on February 22, 2025, in the United States, based on the settlement and licensing agreement with Janssen Biotech Inc.
• PYZCHIVA will be commercialized by Sandoz in the US

INCHEON, South Korea, July 01, 2024 (GLOBE NEWSWIRE) -- Samsung Bioepis Co., Ltd. announced today that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for PYZCHIVA® (ustekinumab-ttwe) subcutaneous injection and intravenous infusion as a biosimilar to Stelara¹ (ustekinumab). PYZCHIVA has been approved for the treatment of moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderately to severely active Crohn’s disease, and moderately to severely active ulcerative colitis. Additionally, a provisional determination was granted for PYZCHIVA’s interchangeability.

“The FDA approval of PYZCHIVA as a biosimilar to Stelara is an important milestone for patients living with inflammatory conditions, as biosimilars can offer more choice and access to biologic treatments,” said Byoung In Jung, Vice President and Regulatory Affairs Team Leader at Samsung Bioepis. “In addition, biosimilars have a potential to reduce the financial burden of healthcare systems, especially in the US where biologics account for more than 46% of the annual drug spending. We will continue to reinforce our commitment to widen access to medicines by advancing our biosimilar pipeline for the benefits of patients, healthcare providers, and healthcare systems around the world,” she added.

The FDA’s approval of PYZCHIVA is based on a totality of evidence including analytical, non-clinical and clinical data demonstrating biosimilarity to Stelara, with no clinically meaningful differences in terms of safety, purity and potency: The randomized, double-blind, three-arm, parallel-group, single-dose Phase 1 clinical study (NCT04772274) demonstrated pharmacokinetics (PK) equivalence and comparable safety, tolerability, immunogenicity profiles between PYZCHIVA (SB17) and Stelara in healthy volunteers. The randomized, double-blind, multicenter Phase 3 clinical study (NCT04967508), conducted in patients with moderate to severe plaque psoriasis, demonstrated biosimilarity of SB17 with Stelara through equivalent efficacy and comparable safety and PK profiles up to Week 28 and these primary results were published in the Journal of the American Academy of Dermatology.² In addition, the Phase 3 study demonstrated biosimilarity of SB17 to Stelara up to week 28 in terms of efficacy, safety, pharmacokinetics, and immunogenicity, and these data were presented at the 2024 American Academy of Dermatology (AAD) Annual Meeting in March 2024.³

PYZCHIVA, developed by Samsung Bioepis, will be commercialized by Sandoz in the United States. Samsung Bioepis and Sandoz entered into a commercialization agreement for SB17 (PYZCHIVA) in September 2023 for the US, Canada, European Economic Area (EEA), Switzerland, and United Kingdom (UK). In the US, the license period for PYZCHIVA will begin on February 22, 2025, according to the settlement and license agreement between Samsung Bioepis and Janssen Biotech Inc.

Samsung Bioepis has a total of 11 biosimilars in its products and pipeline portfolio across immunology, oncology, ophthalmology, hematology, nephrology, and endocrinology. Samsung Bioepis has seven biosimilars approved in the US and four commercially available as of June 2024.

About PYZCHIVA^® (ustekinumab-ttwe) injection, for subcutaneous (45 mg/0.5 mL and 90 mg/mL) or intravenous (130 mg/26 mL solution) use

PYZCHIVA (ustekinumab-ttwe) is indicated for:

• Plaque Psoriasis: PYZCHIVA is indicated for the treatment of adults and pediatric patients 6 years of age and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
• Psoriatic Arthritis: PYZCHIVA is indicated for the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.
• Crohn’s Disease: PYZCHIVA is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease.
• Ulcerative Colitis: PYZCHIVA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

SELECTED IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS PYZCHIVA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in PYZCHIVA.

WARNINGS AND PRECAUTIONS

Infections Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab products.

Serious infections requiring hospitalization, or otherwise clinically significant infections, reported in clinical studies included the following:

• Plaque Psoriasis: diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis and urinary tract infections.
• Psoriatic arthritis: cholecystitis.
• Crohn’s disease: anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeria meningitis.
• Ulcerative colitis: gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.

Avoid initiating treatment with PYZCHIVA in patients with any clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of PYZCHIVA in patients with a chronic infection or a history of recurrent infection.

Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with PYZCHIVA and discontinue PYZCHIVA for serious or clinically significant infections until the infection resolves or is adequately treated.

Theoretical Risk for Vulnerability to Particular Infections Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients.

It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with ustekinumab products may be susceptible to these types of infections. Consider appropriate diagnostic testing (e.g., tissue culture, stool culture, as dictated by clinical circumstances).

Pre-treatment Evaluation for Tuberculosis Evaluate patients for tuberculosis infection prior to initiating treatment with PYZCHIVA.

Avoid administering PYZCHIVA to patients with active tuberculosis infection. Initiate treatment of latent tuberculosis prior to administering PYZCHIVA. Consider anti-tuberculosis therapy prior to initiation of PYZCHIVA in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving PYZCHIVA for signs and symptoms of active tuberculosis during and after treatment.

Malignancies Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among subjects who received ustekinumab in clinical studies. In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy.

The safety of ustekinumab products has not been evaluated in patients who have a history of malignancy or who have a known malignancy.

There have been post-marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving PYZCHIVA for the appearance of non-melanoma skin cancer. Closely follow patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment

Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue PYZCHIVA.

Posterior Reversible Encephalopathy Syndrome (PRES) Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab product initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab products.

Monitor all patients treated with PYZCHIVA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue PYZCHIVA.

Immunizations Prior to initiating therapy with PYZCHIVA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with PYZCHIVA should avoid receiving live vaccines. Avoid administering BCG vaccines during treatment with PYZCHIVA or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving PYZCHIVA because of the potential risk for shedding from the household contact and transmission to patient.

Non-live vaccinations received during a course of PYZCHIVA may not elicit an immune response sufficient to prevent disease.

Noninfectious Pneumonia Cases of interstitial pneumonia, eosinophilic pneumonia and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and in certain cases administration of corticosteroids. If diagnosis is confirmed, discontinue PYZCHIVA and institute appropriate treatment.

Most common adverse reactions are:

• Psoriasis (≥3%): nasopharyngitis, upper respiratory tract infection, headache, and fatigue.
• Crohn’s Disease, induction (≥3%): vomiting.
• Crohn’s Disease, maintenance (≥3%): nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis.
• Ulcerative colitis, induction (≥3%): nasopharyngitis
• Ulcerative colitis, maintenance (≥3%): nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea

Please see Full Prescribing Information for PYZCHIVA™ (ustekinumab-ttwe) HERE,which includes the Boxed Warning, Medication Guide and Instructions for Use.

About Samsung Bioepis Co., Ltd. Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare that is accessible to everyone. Through innovations in product development and a firm commitment to quality, Samsung Bioepis aims to become the world’s leading biopharmaceutical company. Samsung Bioepis continues to advance a broad pipeline of biosimilar candidates that cover a spectrum of therapeutic areas, including immunology, oncology, ophthalmology, hematology, nephrology, and endocrinology. For more information, please visit: www.samsungbioepis.com and follow us on social media – X, LinkedIn.

Media Contact Yoon Kim, yoon1.kim@samsung.com Anna Nayun Kim, nayun86.kim@samsung.com

____________________________

¹ Stelara is a trademark of Johnson & Johnson.

² Steven R. Feldman, et al. A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis. Journal of the American Academy of Dermatology. 2024. ISSN 0190-9622. https://doi.org/10.1016/j.jaad.2024.04.045.

³ Samsung Bioepis News Release. Samsung Bioepis Presents Two Abstracts for Its Immunology Portfolio at the 2024 American Academy of Dermatology (AAD) Annual Meeting. March 9, 2024. https://www.globenewswire.com/news-release/2024/03/09/2843392/0/en/Samsung-Bioepis-Presents-Two-Abstracts-for-Its-Immunology-Portfolio-at-the-2024-American-Academy-of-Dermatology-AAD-Annual-Meeting.html. Accessed June 2024