Biosimilarity study evidence | Selarsdi™ (ustekinumab-aekn)

Study design¹*

Graphic depicting the study design for the SELARSDI biosimilarity clinical trial

Multicenter, double-blind, randomized, active-control study evaluating the efficacy, pharmacokinetics, immunogenicity, and safety of SELARSDI and Stelara in patients with moderate to severe chronic plaque psoriasis
Stage 1: 581 patients randomized 1:2 to SELARSDI or Stelara and dosed on Day 1 (Week 1), Week 4, and then every 12 weeks through Week 40 (unless withdrawn from the study)
Stage 2: Patients initially receiving Stelara rerandomized 1:1 at Week 16 to continue receiving Stelara (n=189) or be switched to SELARSDI (n=192), and patients initially receiving SELARSDI (n=193) continued on SELARSDI
At Week 28, patients who were nonresponsive (<50% improvement in PASI at Week 28) were not administered further study treatment but were encouraged to complete end-of-study assessments at Week 52
At end of study at Week 52, responders underwent final study assessments, while nonresponders who remained in the study underwent only safety and immunogenicity assessments

Primary endpoint¹

Percent improvement in PASI from baseline to Week 12

Secondary endpoints¹

Percent PASI score improvement at additional time points through Week 52
PASI50, PASI75, PASI90, and PASI100 response rates at Weeks 4, 8, 12, 16, 28, 40, and 52
Comparisons of safety, tolerability, immunogenicity, and serum trough concentrations at steady-state

*Study used EU-approved Stelara.

PASI=Psoriasis Area and Severity Index; PASI50=50% improvement in PASI; PASI75=75% improvement in PASI; PASI90=90% improvement in PASI; PASI100=100% improvement in PASI.

SELARSDI demonstrated highly similar improvements in PASI to Stelara¹

PERCENT IMPROVEMENT IN PASI FROM BASELINE TO WEEK 16 (STAGE 1)*

Chart showing similar improvement in PASI for SELARSDI and Stelara through Week 16 of the biosimilarity study

Percent PASI improvement at Week 12: 87.3% for SELARSDI and 86.8% for Stelara (90% CI, -2.14 to 3.01; 95% CI, -2.63 to 3.50)
Similar PASI improvements were observed in the subset of patients weighing ≤100 kg: 86.9% for SELARSDI and 86.8% for Stelara (90% CI, -2.71 to 2.89; 95% CI, -3.25 to 3.43)

Improvements in PASI were sustained up to 52 weeks across treatment groups¹

LONG-TERM PERCENT IMPROVEMENT IN PASI THROUGH WEEK 52 (STAGE 2)*

Chart showing similar improvement in PASI for SELARSDI and Stelara through Week 52 of the biosimilarity study

Percent PASI improvement was comparable in patients who switched from Stelara to SELARSDI and in those who
continued on their original treatments

No clinically significant differences in PASI50, PASI75, PASI90, and PASI100 response rates^1,2*

PASI50, PASI75, PASI90, and PASI100 response rates were similar between SELARSDI- and Stelara-treated patients
through Week 16
PASI50, PASI75, PASI90, and PASI100 response rates remained comparable in patients who switched from Stelara to
SELARSDI and in those who remained on their original treatments

*Study used EU-approved Stelara.

CI=confidence interval; PASI=Psoriasis Area and Severity Index; PASI50=50% improvement in PASI; PASI75=75% improvement in PASI; PASI90=90% improvement in PASI;
PASI100=100% improvement in PASI; SD=standard deviation.

Pharmacokinetics equivalence was demonstrated out to Week 52¹

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS FROM BASELINE TO WEEK 16*

Chart showing similar mean ustekinumab serum concentrations for SELARSDI and Stelara through Week 16 of the biosimilarity study

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS OVER TIME*

Chart showing similar mean ustekinumab serum concentrations for SELARSDI and Stelara through Week 52 of the biosimilarity study

*Study used EU-approved Stelara.

SELARSDI demonstrated comparable immunogenicity to Stelara¹

Prior to switching at Week 16, there were higher binding ADA frequencies in the Stelara-treated patients (48.2%) than the SELARSDI-treated patients (25.4%); this trend was less pronounced in the second part of the study (26.7% vs 21.2%, respectively)
Of these, 31% of the Stelara-treated patients and 26.5% of the SELARSDI-treated patients had NAbs prior to switching, with NAb frequencies remaining consistent over time (22.9% and 33.3%, respectively, at the end of the study)
Numerical differences in the frequency of binding ADAs and NAbs had no clinically meaningful impact on the study treatments’ efficacy, safety, or PK profiles

POSITIVE ANTIBODY INCIDENCE UP TO WEEK 16*

Chart showing positive antibody incidence for SELARSDI and Stelara through Week 16 of the biosimilarity study

POSITIVE ANTIBODY INCIDENCE OVER TIME*

Chart showing positive antibody incidence for SELARSDI and Stelara through Week 50 of the biosimilarity study

*Study used EU-approved Stelara.

ADA=antidrug antibody; NAb=neutralizing antibody; PK=pharmacokinetics.

SELARSDI and Stelara had no clinically meaningful differences in safety¹

TEAEs*

	Stage 1 (Weeks 1-16) n (%)		Stage 2 (Weeks 16-28) n (%)			Stage 2 (Weeks 28-52) n (%)
	SELARSDI n=194	Stelara n=387	SELARSDI/ SELARSDI n=193	Stelara/ SELARSDI n=192	Stelara/ Stelara n=189	SELARSDI/ SELARSDI n=191	Stelara/ SELARSDI n=184	Stelara/ Stelara n=184
Any TEAE	67 (35.5)	130 (33.6)	21 (10.9)	30 (15.6)	29 (15.3)	32 (16.8)	42 (22.8)	39 (21.2)
Treatment-related TEAEs	10 (5.2)	37 (9.6)	0	5 (2.6)	2 (1.1)	0	3 (1.6)	6 (3.3)
TEAEs leading to discontinuation from study treatment phase	0	3 (0.8)	1 (0.5)	3 (1.6)	4 (2.1)	0	0	1 (0.5)
TEAEs of special interest	3 (1.5)	16 (4.1)	0	2 (1.0)	1 (0.5)	0	3 (1.6)	2 (1.1)
Summary of AEs of special interest by primary system organ class and preferred term
General disorders and administration-site conditions	2 (1.0)	11 (2.8)	0	2 (1.0)	1 (0.5)	0	2 (1.1)	2 (1.1)
Injection-site reactions	2 (1.0)	9 (2.3)	0	1 (0.5)	1 (0.5)	0	1 (0.5)	2 (1.1)
Injection-site pain	0	1 (0.3)	0	0	0	0	1 (0.5)	0
Injection-site hematoma	0	1 (0.3)	0	1 (0.5)	0	0	0	0
Vascular disorders	1 (0.5)	2 (0.5)	0	0	0	0	0	0
Hematoma	1 (0.5)	2 (0.5)	0	0	0	0	0	0
Skin and subcutaneous tissue disorder	0	2 (0.5)	0	0	0	0	0	0
Pruritus	0	2 (0.5)	0	0	0	0	0	0
Neoplasms benign, malignant, and unspecified (incl. cysts and polyps)	0	1 (0.3)	0	0	0	0	0	0
Pancreatic carcinoma metastatic	0	1 (0.3)	0	0	0	0	0	0
Infections and infestations	0	0	0	0	0	0	1 (0.5)	0
Lower respiratory tract infection	0	0	0	0	0	0	1 (0.5)	0

Any TEAE

Treatment-related TEAEs

TEAEs leading to discontinuation from study treatment phase

TEAEs of special interest

Summary of AEs of special interest by
primary system organ class and preferred term

General disorders and administration-site conditions

Injection-site reactions

Injection-site pain

Injection-site hematoma

Vascular disorders

Hematoma

Skin and subcutaneous tissue disorder

Pruritus

Neoplasms benign, malignant, and unspecified (incl. cysts and polyps)

Pancreatic carcinoma metastatic

Infections and infestations

Lower respiratory tract infection

During the first 16 weeks of treatment
Most TEAEs were mild in nature, with a similar percentage of patients across treatment groups reporting TEAEs.

From Week 16 through end of study
Safety profiles remained similar between the treatment groups—including in patients who were switched from Stelara to SELARSDI at Week 16.

*Study used EU-approved Stelara.

AE=adverse event; TEAE=treatment-emergent adverse event.

EXPLORE THE PHARMACOKINETICS STUDY FOR SELARSDI

IMPORTANT SAFETY INFORMATION

SELARSDI™ (ustekinumab-aekn) Injection is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in SELARSDI.

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 were reported. In patients with plaque psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.

Treatment with SELARSDI should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of SELARSDI 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 SELARSDI and discontinue SELARSDI 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 diagnostic testing, eg, tissue culture, stool culture, as dictated by clinical circumstances.

Pre-Treatment Evaluation of Tuberculosis (TB)

Evaluate patients for TB prior to initiating treatment with SELARSDI. Do not administer SELARSDI to patients with active TB infection. Initiate treatment of latent TB before administering SELARSDI. Consider anti-tuberculosis therapy prior to initiation of SELARSDI in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving SELARSDI for signs and symptoms of active TB during and after treatment.

Malignancies

Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among patients who received ustekinumab in clinical trials. 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 (NMSC). All patients receiving SELARSDI, especially those greater than 60 years of age or those with a history of Psoralen plus ultraviolet A (PUVA) or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.

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 SELARSDI.

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 SELARSDI for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue SELARSDI.

Immunizations

Prior to initiating therapy with SELARSDI, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with SELARSDI should not receive live vaccines. Avoid administering BCG vaccines during treatment with SELARSDI 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 SELARSDI because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of SELARSDI may not elicit an immune response sufficient to prevent disease.

Concomitant Therapies

The safety of ustekinumab products, in combination with other biologic immunosuppressive agents or phototherapy has not been evaluated in clinical trials of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab.

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 SELARSDI and institute appropriate treatment.

Allergen Immunotherapy

Ustekinumab products have not been evaluated in patients who have undergone allergy immunotherapy. Ustekinumab products may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis.

Most Common Adverse Reactions

The most common adverse reactions for plaque psoriasis (≥3%) were nasopharyngitis, upper respiratory tract infection, headache, and fatigue. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis. The most common adverse reaction for Crohn’s disease induction (≥3%) was vomiting. The most common adverse reactions for Crohn’s disease maintenance (≥3%) were nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. The most common adverse reaction for ulcerative colitis induction (≥3%) was nasopharyngitis. The most common adverse reactions for ulcerative colitis maintenance (≥3%) were nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea.

INDICATIONS

SELARSDI™ (ustekinumab-aekn) Injection, is a human interleukin-12 and -23 antagonist 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.
the treatment of adults and pediatric patients 6 years of age and older with active psoriatic arthritis.
the treatment of adult patients with moderately to severely active Crohn’s disease.
the treatment of adult patients with moderately to severely active ulcerative colitis.

Please click here for full Prescribing Information for SELARSDI.

REFERENCE:

1. Feldman SR, Reznichenko N, Berti F, et al. Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. Expert Opin Biol Ther. 2023;23(8):759-771.

There were no clinically meaningful differences between SELARSDI™ and Stelara^®1

Study design¹*

Primary endpoint¹

Secondary endpoints¹

SELARSDI demonstrated highly similar improvements in PASI to Stelara¹

PERCENT IMPROVEMENT IN PASI FROM BASELINE TO WEEK 16 (STAGE 1)*

Improvements in PASI were sustained up to 52 weeks across treatment groups¹

LONG-TERM PERCENT IMPROVEMENT IN PASI THROUGH WEEK 52 (STAGE 2)*

No clinically significant differences in PASI50, PASI75, PASI90, and PASI100 response rates^1,2*

Pharmacokinetics equivalence was demonstrated out to Week 52¹

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS FROM BASELINE TO WEEK 16*

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS OVER TIME*

SELARSDI demonstrated comparable immunogenicity to Stelara¹

POSITIVE ANTIBODY INCIDENCE UP TO WEEK 16*

POSITIVE ANTIBODY INCIDENCE OVER TIME*

SELARSDI and Stelara had no clinically meaningful differences in safety¹

REFERENCE:

REFERENCES:

There were no clinically meaningful differences between SELARSDI™ and Stelara®1

Study design1*

Primary endpoint1

Secondary endpoints1

SELARSDI demonstrated highly similar improvements in PASI to Stelara1

PERCENT IMPROVEMENT IN PASI FROM BASELINE TO WEEK 16 (STAGE 1)*

Improvements in PASI were sustained up to 52 weeks across treatment groups1

LONG-TERM PERCENT IMPROVEMENT IN PASI THROUGH WEEK 52 (STAGE 2)*

No clinically significant differences in PASI50, PASI75, PASI90, and PASI100 response rates1,2*

Pharmacokinetics equivalence was demonstrated out to Week 521

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS FROM BASELINE TO WEEK 16*

MEAN SERUM TROUGH USTEKINUMAB CONCENTRATIONS OVER TIME*

SELARSDI demonstrated comparable immunogenicity to Stelara1

POSITIVE ANTIBODY INCIDENCE UP TO WEEK 16*

POSITIVE ANTIBODY INCIDENCE OVER TIME*

SELARSDI and Stelara had no clinically meaningful differences in safety1

REFERENCE:

REFERENCES:

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There were no clinically meaningful differences between SELARSDI™ and Stelara^®1

Study design¹*

Primary endpoint¹

Secondary endpoints¹

SELARSDI demonstrated highly similar improvements in PASI to Stelara¹

Improvements in PASI were sustained up to 52 weeks across treatment groups¹

No clinically significant differences in PASI50, PASI75, PASI90, and PASI100 response rates^1,2*

Pharmacokinetics equivalence was demonstrated out to Week 52¹

SELARSDI demonstrated comparable immunogenicity to Stelara¹

SELARSDI and Stelara had no clinically meaningful differences in safety¹