Immunoglobulin G1, anti-(human interleukin 23) (human-Mus musculus monoclonal heavy chain), disulfide with human-Mus musculus monoclonal light chain, dimer
CAS 1326244-10-3, BLA 761067
Tildrakizumab (SCH 900222/MK-3222)
ILUMYA; MK-3222; SCH-900222; SUNPG 1622; SUNPG 1622 I; SUNPG 1623 I; SUNPG 1623 II; SUNPG 1623 III; SUNPG 1623 IV; SUNPG1623; Tildrakizumab-asmn
DRUG BANK https://www.drugbank.ca/drugs/DB14004
Company Sun Pharmaceuticals
Approval Status FDA Approved March 2018 FOR Psoriasis, plaque
Treatments plaque psoriasis
Protein chemical formulaC6426H9918N1698O2000S46
Protein average weight144400.0 DaSequences
>Tildrakizumab Sequence MLGSRAVMLLLLLPWTAQGRAVPGGSSPAWTQCQQLSQKLCTLAWSAHPLVGHMDLREEG DEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIHQGLIFYEKLLGSDIFTGEPSLLPDSP VGQLHASLLGLSQLLQPEGHHWETQQIPSLSPSQPWQRLLLRFKILRSLQAFVAVAARVF AHGAATLSP
|Source||Humanized (from mouse)|
|Chemical and physical data|
|Molar mass||144.4 kg/mol|
- Originator Schering-Plough
- Developer Almirall S.A.; Merck & Co; Schering-Plough; Sun Pharmaceutical Industries
- Class Antipsoriatics; Monoclonal antibodies
- Mechanism of Action Interleukin 23 inhibitors
- Orphan Drug StatusNo
- New Molecular EntityYes
Highest Development Phases
- Registered Plaque psoriasis
- Phase II Ankylosing spondylitis; Psoriatic arthritis
- Discontinued Autoimmune disorders
Most Recent Events
- 21 Mar 2018 Registered for Plaque psoriasis in USA (SC) – First global approval
- 16 Feb 2018 Adverse events data from two phase III trials (reSURFACE 1 and 2) in chronic Plaque psoriasis presented at the 76th Annual Meeting of the American Academy of Dermatology (AAD-2018)
- 16 Feb 2018 Pharmacokinetics data from population PK model in healthy volunteers and patients with psoriasis presented at the 76th Annual Meeting of the American Academy of Dermatology (AAD-2018)
Ilumya (tildrakizumab-asmn) is an interleukin-23 antagonist.
Humanized monoclonal IgG1-kappa antibody against IL-23p19; produced in CHO cells
Immunoglobulin G1, anti-(human interleukin 23) (human-Mus musculus monoclonal heavy chain), disulfide with human-Mus musculus monoclonal light chain, dimer
Ilumya is specifically indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Ilumya is supplied as a solution for subcutaneous injection. The recommended dose is 100 mg at Weeks 0, 4, and every twelve weeks thereafter.
Tildrakizumab (Ilumya) is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders. In the United States, it is approved for the treatment of moderate-to-severe plaque psoriasis.
Tildrakizumab was designed to block interleukin-23, a cytokine that plays an important role in managing the immune system and autoimmune disease. Originally developed by Schering-Plough, this drug is now part of Merck‘s clinical program, following that company’s acquisition of Schering-Plough.
Sun Pharmaceutical acquired worldwide rights to tildrakizumab for use in all human indications from Merck in exchange for an upfront payment of U.S. $80 million. Upon product approval, Sun Pharmaceutical will be responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the approved product. 
As of March 2014, the drug was in phase III clinical trials for plaque psoriasis. The two trials enrolled nearly 2000 patients. 
In 2016, tildrakizumab became the first IL-23p19 inhibitor to demonstrate positive results in Phase-3 clinical trials for the treatment of moderate-to-severe plaque psoriasis, further validating the importance of the role of IL-23 in psoriasis. Sun Pharma signed a licensing pact with Spain’s Almirall for marketing tildrakizumab in Europe 
In March 2018, it was approved by the Food and Drug Administration for the treatment of moderate-to-severe plaque psoriasis as an injection for subcutaneous use in the United States.
In 2014, Sun Pharma acquired worldwide rights to tildrakizumab from Merck; upon product approval, Sun Pharma is responsible for regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the product. In 2016, Almirall sublicensed the product for the development and marketing in Europe for the treatment of psoriasis.
- Ustekinumab, a monoclonal antibody targeting both IL-12 and IL-23 and used to treat plaque psoriasis, launched in the United States under the brand name Stelara
- Guselkumab, another experimental, IL-23-specific monoclonal antibody. (FDA approved in 2017)
- Risankizumab, another experimental, IL-23-specific monoclonal antibody. (In Phase 3 clinical trials for plaque psoriasis as of 2017)
- Jump up^ Statement On A Nonproprietary Name Adopted By The USAN Council – Tildrakizumab, American Medical Association.
- ^ Jump up to:a b “FDA approves Ilumya for plaque psoriasis”. National Psoriasis Foundation. March 22, 2018.
- Jump up^ http://www.merck.com/licensing/our-partnership/sunpharma_partnership.html
- Jump up^ http://clinicaltrials.gov/ct2/show/NCT01729754?term=SCH-900222&phase=2&fund=2&rank=1
- Jump up^ http://clinicaltrials.gov/ct2/show/NCT01722331?term=SCH-900222&phase=2&fund=2&rank=2
- Jump up^ http://www.business-standard.com/content/b2b-pharma/sun-pharma-signs-licensing-pact-with-spain-s-almirall-for-tildrakizumab-in-europe-116072800225_1.html
Mechanism of Action
Tildrakizumab is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines.
FDA APPROVAL DATA
Please refer to your Biologics License Application (BLA) dated and received March 23, 2017 and your amendments, submitted under section 351(a) of the Public Health Service Act for ILUMYA (tildrakizumab-asmn) injection. We also refer to our approval letter dated March 20, 2018 which contained the following error: the Final Report Submission date was incorrectly listed for postmarketing requirement 3357-3. This replacement approval letter incorporates the correction of the error. The effective approval date will remain March 20, 2018, the date of the original approval letter.
LICENSING We have approved your BLA for ILUMYA (tildrakizumab-asmn) effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, ILUMYA under your existing Department of Health and Human Services U.S. License No. 0002. ILUMYA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
MANUFACTURING LOCATIONS Under this license, you are approved to manufacture ILUMYA drug substance at . The final formulated drug product will be manufactured, filled, labeled, and packaged at MSD Ireland, Carlow, Ireland. You may label your product with the proprietary name, ILUMYA, and market it in 100 mg/1 mL single-dose prefilled syringe
DATING PERIOD The dating period for ILUMYA drug product shall be 36 months from the date of manufacture when stored at 2-8°C. The date of manufacture shall be defined as the date of final sterile filtration of the formulated drug product. The dating period for your drug substance shall be months from the date of manufacture when stored at We have approved the stability protocols in your license application for the purpose of extending the expiration dating period of your drug substance and drug product under 21 CFR 601.12.
Tildrakizumab (SCH 900222/MK-3222) targets the p19 subunit of IL-23. The mAb was developed by Schering-Plough, which was acquired by Merck & Co. in 2009, and it was then licensed by Merck to Sun Pharmaceutical Industries Ltd in September 2014. Clinical development and regulatory activities will be conducted by Merck, but funded by Sun Pharma. As of October 2014, the safety and efficacy of tildrakizumab are being evaluated in 2 Phase 3 studies that are ongoing but not recruiting patients. Both studies include patients with moderate-to-severe chronic plaque psoriasis and subcutaneously administered drug. The 52-week Phase 3 NCT01729754 study has 4 arms (200 mg tildrakizumab; 100 mg tildrakizumab; 50 mg etanercept; and placebo only), and includes an optional long-term safety extension study. The estimated enrollment is 1050, and the estimated primary completion date is October 2019. The 64-week Phase 3 NCT01722331 study is evaluating the effects of either 200 mg or 100 mg tildrakizumab to placebo; it includes an optional long-term safety extension study. The estimated enrollment is 885, and the estimated primary completion date is June 2015.
Sun Pharma Announces U.S. FDA Approval of ILUMYA™ (tildrakizumab-asmn) for the Treatment of Moderate-to-Severe Plaque Psoriasis
MUMBAI, India and PRINCETON, N.J., March 21, 2018 /PRNewswire/ — Sun Pharmaceutical Industries Ltd. (Reuters: SUN.BO, Bloomberg: SUNP IN, NSE: SUNPHARMA, BSE: 524715, “Sun Pharma” and includes its subsidiaries and/or associate companies) today announced that the U.S. Food and Drug Administration (FDA) has approved ILUMYA™ (tildrakizumab-asmn) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. ILUMYA selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor leading to inhibition of the release of pro-inflammatory cytokines and chemokines. ILUMYA is administered at a dose of 100 mg by subcutaneous injection every 12 weeks, after the completion of initial doses at weeks 0 and 4. ILUMYA is contraindicated in patients with a previous serious hypersensitivity reaction to tildrakizumab or to any of the excipients.
“With the approval of ILUMYA and our long-standing commitment in dermatology, we are focused on making a difference for people living with moderate-to-severe plaque psoriasis,” said Abhay Gandhi, President and Chief Executive Officer, North America, Sun Pharma. “We are committed to working with all relevant stakeholders to make ILUMYA available to appropriate people with plaque psoriasis.”
The FDA approval of ILUMYA for the treatment of adults with moderate-to-severe plaque psoriasis was supported by data from the pivotal Phase-3 reSURFACE clinical development program. In the two multicenter, randomized, double-blind, placebo-controlled trials (reSURFACE 1 and reSURFACE 2), 926 adult patients were treated with ILUMYA (N=616) or placebo (N=310). Results from these studies were published in The Lancet in July 2017, with primary endpoints presented at the 25th European Academy of Dermatology and Venereology (EADV) Congress.
Both Phase-3 studies met the primary efficacy endpoints, demonstrating significant clinical improvement with ILUMYA 100 mg compared to placebo when measured by at least 75 percent of skin clearance (Psoriasis Area Sensitivity Index or PASI 75) and Physician’s Global Assessment (PGA) score of “clear” or “minimal” at week 12 after two doses.
Efficacy Primary Endpoint at Week 12 in Adults with Plaque Psoriasis (NRI*)
reSURFACE 1 Study
reSURFACE 2 Study
ILUMYA 100 mg
ILUMYA 100 mg
PGA of “clear” (0) or “minimal” (1)†
* NRI = Non-Responder Imputation † Co-Primary Endpoints
Of the patients in the reSURFACE 1 study 74 percent (229 patients) achieved 75 percent skin clearance at week 28 after three doses, and 84 percent of patients who continued receiving ILUMYA 100 mg maintained PASI 75 at week 64 compared to 22 percent of patients who were re-randomized to placebo. In addition, 69 percent of the patients receiving ILUMYA 100 mg who had a PGA score of “clear” or “minimal” at week 28 maintained this response at week 64 compared to 14 percent of patients who were re-randomized to placebo.
Full Prescribing Information and Medication Guide for ILUMYA are attached:
IMPORTANT SAFETY INFORMATION (continued)
Cases of angioedema and urticaria occurred in ILUMYA treated subjects in clinical trial. If a serious hypersensitivity reaction occurs, discontinue ILUMYA immediately and initiate appropriate therapy.
ILUMYA may increase the risk of infection. Treatment with ILUMYA 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 prescribing ILUMYA in patients with a chronic infection or a history of recurrent infection. Instruct patients receiving ILUMYA to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection, or is not responding to standard therapy, closely monitor and discontinue ILUMYA until the infection resolves.
Evaluate patients for TB infection prior to initiating treatment with ILUMYA. Initiate treatment of latent TB prior to administering ILUMYA. Monitor patients for signs and symptoms of active TB during and after ILUMYA treatment. Do not administer ILUMYA to patients with active TB infection.
Prior to initiating ILUMYA, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with ILUMYA.
The most common (≥1%) adverse reactions associated with ILUMYA include upper respiratory infections, injection site reactions, and diarrhea. Adverse reactions that occurred at rates less than 1% but greater than 0.1% in the ILUMYA group and at a higher rate than in the placebo group included dizziness and pain in extremity.
About the Phase-3 reSURFACE Trials
The Phase-3 studies (reSURFACE 1 and reSURFACE 2) were randomized, placebo-controlled, multicenter, three-part studies designed to demonstrate efficacy of ILUMYA in moderate-to-severe plaque psoriasis compared to placebo and comparative drug and to assess safety and tolerability. Part one of the studies randomized patients into three or four treatment arms, including ILUMYA 100 mg, ILUMYA 200 mg, placebo and etanercept (reSURFACE 2 only). After Week 12, patients on placebo were then re-randomized into ILUMYA 100 mg and 200 mg treatment arms to proceed into part two of the studies. Finally, in part three of the reSURFACE 1 study, responders (PASI ≥75) and partial responders (PASI ≥50 and PASI <75) to ILUMYA were re-randomized after Week 28 to continue the same treatment, a different dose of ILUMYA or placebo. Partial and non-responders to etanercept were treated with ILUMYA 200 mg in part three of the reSURFACE 2 study. Patients with guttate, erythrodermic, or pustular psoriasis were excluded.
Psoriasis is a chronic immune disease that appears on the skin. It is a non-contagious disorder that speeds the growth cycle of skin cells1 and results in thick scaly areas of skin2. The most common form, affecting about 80 to 90 percent of people living with psoriasis, is called plaque psoriasis3. It appears as red, raised areas of skin covered with flaky white scales, which may be itchy and painful and can crack and bleed2. Many people with plaque psoriasis continue to struggle with the ongoing, persistent nature of this chronic disease.
About Sun Dermatology
Sun Dermatology (the branded dermatology division of a wholly owned subsidiary of Sun Pharma) is committed to expanding its dermatology portfolio to bring healthcare providers and patients around the world more treatment options and ongoing support for conditions like moderate-to-severe plaque psoriasis. Sun Pharma, along with its subsidiaries, is ranked fourth in dermatology prescription volume within the U.S. per IMS and is fifth largest specialty generic pharmaceutical company globally. In addition to ILUMYA, Sun Dermatology is comprised of several branded products indicated for the treatment of acne and actinic keratosis with a focus on other dermatologic conditions.
About Sun Pharma, Merck & Co., Inc., Kenilworth, NJ, USA, Agreement
Sun Pharmaceutical Industries Ltd.’s wholly owned subsidiary licensed worldwide rights to ILUMYA from a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, in 2014. Funded by a Sun Pharma subsidiary, Merck & Co., Inc., Kenilworth, NJ, USA was responsible for the completion of Phase-3 trials and submission of a Biologics License Application to the United States Food and Drug Administration (FDA), as well as manufacturing finished goods to support Sun Pharma’s initial product launch. Sun Pharma will be responsible for all post-approval regulatory activities, including subsequent submissions, pharmacovigilance, post approval studies, manufacturing and commercialization of the approved product. Sun Pharma will also be responsible for all regulatory, pharmacovigilance, post approval studies, manufacturing and commercialization of approved products for all non-U.S. markets. Merck & Co., Inc., Kenilworth, NJ, USA is eligible to receive milestone payments and royalties on sales of ILUMYA.
About Sun Pharma, Almirall S.A, Europe, Agreement
Sun Pharma and its wholly owned subsidiary and Almirall (Spanish Stock Exchange ticker: ALM) closed on July 2016 a licensing agreement on the development and commercialization of tildrakizumab-asmn for psoriasis in Europe. Under the terms of the licensing agreement, Almirall is able to lead European studies, and participate in larger Global clinical studies for plaque psoriasis indication subject to the terms of the Sun Pharma – Merck & Co., Inc., Kenilworth, NJ, USA agreements, as well as certain cost sharing agreements. Sun Pharma will be eligible to receive development and regulatory milestone payments and, additionally, sales milestone payments and royalties on net sales. Sun Pharma will continue to lead development of tildrakizumab-asmn for other indications, where Almirall will have right of first negotiation for certain indications in Europe. The agreement between Sun Pharma and Almirall remains subject to the exclusive licensing agreement between Sun Pharma and Merck & Co., Inc., Kenilworth, NJ, USA.
About Sun Pharmaceutical Industries Ltd. (CIN – L24230GJ1993PLC019050)
Sun Pharma is the world’s fifth largest specialty generic pharmaceutical company and India’s top pharmaceutical company. A vertically integrated business, economies of scale and an extremely skilled team enable us to deliver quality products in a timely manner at affordable prices. It provides high-quality, affordable medicines trusted by customers and patients in over 150 countries across the world. Sun Pharma’s global presence is supported by 41 manufacturing facilities spread across 6 continents, R&D centres across the globe and a multi-cultural workforce comprising over 50 nationalities. In India, the company enjoys leadership across 11 different classes of doctors with 30 brands featuring amongst top 300 pharmaceutical brands in India. Its footprint across emerging markets covers over 100 markets and 6 markets in Western Europe. Its Global Consumer Healthcare business is ranked amongst Top 10 across 3 global markets. Its API business footprint is strengthened through 14 world class API manufacturing facilities across the globe. Sun Pharma fosters excellence through innovation supported by strong R&D capabilities comprising about 2,000 scientists and R&D investments of approximately 8% of annual revenues. For further information, please visit www.sunpharma.com & follow us on Twitter @SunPharma_Live.
1. National Psoriasis Foundation. Facts about psoriasis. www.psoriasis.org/sites/default/files/for-media/MediaKit.pdf. Accessed on February 22, 2018.
2. National Psoriasis Foundation. About Psoriasis. www.psoriasis.org/about-psoriasis. Accessed on February 22, 2018.
3. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008 May; 58(5):826-50.
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