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Date: 2017-07-20

Type of information: Granting of a Market Authorisation in the EU

Product name: Kyntheum® (EU)/Siliq® (US) (brodalumab

Compound: brodalumab

Therapeutic area: Autoimmune diseases - Dermatological diseases

Action mechanism:

  • monoclonal antibody. Brodalumab is a highly-selective human monoclonal antibody that binds to and blocks signaling via the interleukin-17 (IL-17) receptor subunit A. By binding to this specific receptor subunit on the cells of the skin, rather than targeting free inflammatory mediators, brodalumab blocks the biological activity of several pro-inflammatory IL-17 cytokines involved in plaque formation.
  • In October, 2015, Valeant entered into a collaboration agreement with AstraZeneca under which Valeant has an exclusive license to develop and commercialise brodalumab globally, except in Japan and certain other Asian countries where rights are held by Kyowa Hakko Kirin.
  • In July 2016, AstraZeneca announced an agreement granting LEO Pharma, a specialist in dermatology, exclusive rights to develop and commercialise brodalumab in Europe.

Company: AstraZeneca (UK) Valeant Pharmaceuticals (Canada) Leo Pharma (Denmark)

Disease: moderate-to-severe plaque psoriasis

Latest news:

  • • On July 20, 2017, AstraZeneca and MedImmune announced that its partner LEO Pharma has been granted full marketing authorisation in all 28 EU member countries plus Iceland, Liechtenstein and Norway for Kyntheum® (brodalumab) for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy.
  • The AMAGINE clinical trial programme (AMAGINE 1-3) involved 4,373 patients with moderate-to-severe psoriasis. The psoriasis clinical trials programme for Kyntheum consisted of three clinical trials; AMAGINE-1 (661 patients), AMAGINE-2 (1831 patients) and AMAGINE-3 (1881 patients).
  • In AMAGINE-1, 83% of patients on Kyntheum 210mg achieved PASI 75* compared to 3% of patients treated with placebo at 12 weeks [83.3% (n=185) versus 2.7% (n=6), p<0.001] and 76% of patients achieved sPGA** success versus 1% of patients treated with placebo [75.7% (n=168) versus 1.4% (n=3), p<0.001].12
  • • On May 18, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Kyntheum®, intended for the treatment of psoriasis. The benefits with Kyntheum® are its ability to inhibit the inflammation and clinical symptoms associated with psoriasis. The most common side effects are arthralgia, headache, fatigue, diarrhoea, and oropharyngeal pain.
  • The CHMP positive opinion is based on data from the three AMAGINE Phase III pivotal studies that demonstrated that brodalumab has an effective mechanism of action that delivers clinical benefit and could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of their skin disease. At the 210mg dose, brodalumab was shown to be efficacious in total skin clearance of psoriasis with approximately twice as many patients on brodalumab achieving total skin clearance compared to ustekinumab at week 12 in two replicate comparator trials involving over 2,400 patients.
  • The Marketing Authorisation Application (MAA) for brodalumab in psoriasis was accepted by the European Medicines Agency (EMA) in Q4 2015.
  • • On February 15, 2017, the FDA approved Siliq® (brodalumab) to treat adults with moderate-to-severe plaque psoriasis. Siliq® is administered as an injection. The drug is intended for patients who are candidates for systemic therapy or phototherapy (ultraviolet light treatment) and have failed to respond, or have stopped responding to other systemic therapies. Siliq®’s safety and efficacy were established in three randomized, placebo-controlled clinical trials with a total of 4,373 adult participants with moderate-to-severe plaque psoriasis who were candidates for systemic therapy or phototherapy. More patients treated with Siliq® compared to placebo had skin that was clear or almost clear, as assessed by scoring of the extent, nature and severity of psoriatic changes of the skin.
  • Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq® during clinical trials. Siliq® users with a history of suicidality or depression had an increased incidence of suicidal ideation and behavior compared to users without this history. A causal association between treatment with Siliq and increased risk of suicidal ideation and behavior has not been established. Because of the observed risk of suicidal ideation and behavior, the labeling for Siliq® includes a Boxed Warning and the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Siliq REMS Program.
  • • On July 19, 2016, Valeant Pharmaceuticals announced that the Dermatologic and Ophtalmic Drugs Advisory Committee appointed by the FDA has voted by a margin of 18 to 0 for the approval of brodalumab injection, 210 mg, for adult ptients with moderate-to-severe plaque psoriasis with
  • conditions related to product labeling and post marketing/risk management obligations.
  • • On January 25, 2016, Valeant Pharmaceuticals  announced that the FDA has accepted for review the Biologics License Application (BLA) submitted by AstraZeneca in partnership with Valeant, for brodalumab injection, 210 mg, development for patients with moderate-to-severe plaque psoriasis. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of November 16, 2016.
  • The brodalumab BLA is supported by data from the three AMAGINE Phase III pivotal studies (AMAGINE-1, AMAGINE-2, AMAGINE-3)  The results highlighted that brodalumab has an effective mechanism of action that could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of their skin disease. At the 210 mg dose, brodalumab was shown to be effective in total skin clearance of psoriasis compared to placebo and superior to ustekinumab, a leading approved psoriasis treatment, at week 12 in two replicate comparator trials involving over 3,500 patients.
  • The most common adverse reactions were headache, arthralgia, fatigue, oropharyngeal pain, and diarrhea. Caution should be exercised when prescribing to patients with a history of Crohn's disease. Suicidal ideation and behavior have been reported. The potential risks and benefits should be weighed before using brodalumab in patients with a history of depression and/or suicidal ideation or behavior. Serious infections have occurred therefore caution should be exercised when considering the use of brodalumab in patients with a chronic infection or a history of recurrent infection. Patients should be evaluated for tuberculosis infection prior to initiating treatment.

Patents:

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: 2017-02-15

UE authorization: 2017-07-19

Favourable opinion UE: 2017-05-18

Favourable opinion USA: 2016-07-19

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes