Type of information: Granting of a Market Authorisation in the EU
Product name: Ilumetri®(EU)/Ilumya™ (USA - Australia)
Therapeutic area: Autoimmune diseases - Dermatological diseases - Inflammatory diseases
- monoclonal antibody. Tildrakizumab is an anti-IL-23p19 monoclonal antibody. It selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL23 receptor leading to inhibition of the release of proinflammatory cytokines and chemokines. In clinical studies for the treatment of chronic plaque psoriasis, tildrakizumab demonstrates efficacy in blocking inflammation by blocking IL-23. Other potential indications, which may be evaluated in future, include psoriatic arthritis and Crohn’s disease.
- Ilumetri®/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.
- The drug has been initially developed by Merck&Co. In September 2014, Merck & Co and Sun Pharmaceutical Industries have concluded a licensing agreement for tildrakizumab, (MK-3222).
- In July 2016, Sun Pharma had announced a strategic licensing agreement with Almirall on the development and commercialization of tildrakizumab for psoriasis in Europe.
Company: Merck&Co (USA - NJ) Sun Pharmaceutical Industries (India) Almirall (Spain)
- moderate-to-severe plaque psoriasis
- • On September 17, 2018, Sun Pharma announced that the company has received the Australian Therapeutic Goods Administration (TGA) approval for its speciality product,
Ilumya™ (tildrakizumab) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. The drug is contraindicated in patients with a previous serious hypersensitivity reaction to tildrakizumab or to any of the excipients in Ilumya™, and in patients with clinically important active infections, e.g. active tuberculosis. In Australia, the number of severe chronic plaque psoriasis patients receiving treatment through the Pharmaceutical Benefit Scheme (PBS) with biologics, increased by more than 60% between 2014 and 2016. However, the number treated was less than 30% of the severely affected population. The total PBS expenditure on biologicals for chronic plaque psoriasis (at published prices) was A$121 million in 2016.
- The TGA 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 multicentre, randomized, double-blind, placebo-controlled trials (reSURFACE 1 and reSURFACE 2), 1862 adult patients were enrolled and treated with Ilumya™ (N=1238), etanercept (N=313) 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 or etanercept when measured by at least 75 percent reduction in baseline psoriasis severity (Psoriasis Area Sensitivity Index or PASI 75) and Physician’s Global Assessment (PGA) score of “clear” or “minimal” at week 12 after two doses. The most common adverse reactions observed with Ilumya™ in the pooled data from one Phase 2 and two Phase 3 studies in psoriasis patients for the placebo controlled period (16
weeks for the Phase 2 study and 12 weeks for the Phase 3 studies) were nasopharyngitis, headache, and site injection pain. Most adverse reactions were considered mild and no
adverse reaction led to discontinuation of treatment in >1% of patients.
• On September 18, 2018, Almirall has received the
European Commission (EC) approval for Ilumetri® (tildrakizumab) for the treatment of adults with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy. As indicated by Almirall, roll out of Ilumetri® in Europe will start in the next few
weeks. The approval in Europe is based on the positive results from reSURFACE 1 and 2 phase-3 clinical trials, presented for the first time in October 2016 at the 25th European Academy of Dermatology and Venerology (EADV) Congress in Vienna (Austria). Both pivotal phase-3 clinical trials, which included over 1,800 patients from more than 200 clinical sites worldwide, showed Ilumetri® has a high level of safety and efficacy. According to both studies data, an average of 63% of patients achieved 75% of skin clearance (PASI 75) by week 12 and an average of 78% at week 28. An average of 59% of patients achieved PASI 90 and an average of 30% reached
PASI 100 at week 28. Over a year, more than 92% of patients who responded to Ilumetri® within 28 weeks maintained a PASI 75 response.
- • On July 26, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Ilumetri®, intended for the treatment of moderate to severe plaque psoriasis. Ilumetri® will be available as a 100-mg solution for injection. The benefits with Ilumetri are its ability to reduce the immune response and inflammatory process, and thereby improve the signs and symptoms of patients with moderate to severe plaque psoriasis. The most common side effects are upper respiratory tract infections, gastroenteritis, nausea, diarrhea, headache, injection site pain and back pain.
- • On March 20, 2018, the 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. 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. 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
- • On May 24, 2017, Sun Pharmaceutical Industries announced the FDA acceptance of the Biologics License Application (BLA) for tildrakizumab for the treatment of moderate-to-severe plaque psoriasis. The BLA filing for tildrakizumab was submitted by Merck&Co.
The BLA filing for tildrakizumab with the FDA is based on two pivotal Phase III trials (reSURFACE 1 and 2) which included over 1,800 patients across more than 200 clinical trial sites, including some patients who have been treated with tildrakizumab for up to three and a half years. Data from these trials were most recently presented at the 2017 American Academy of Dermatology (AAD) Annual Meeting in March and previously presented at the 25th European Academy of Dermatology and Venereology Congress.
- • On March 24, 2017, Almirall and Sun Pharmaceutical Industries announced the validation of the Regulatory Filing of tildrakizumab with the European Medicines Agency (EMA) by Almirall. The filing includes efficacy and safety data from the pivotal Phase III clinical trials (reSURFACE 1 and 2) that included over 1,800 patients across more than 200 clinical
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-03-20
UE authorization: 2018-09-17
Favourable opinion UE: 2018-07-26
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: