Edition of 26 July 2018

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended nine medicines for approval, including six orphan medicines, at its June 2018 meeting.

The CHMP recommended granting marketing authorisations for:

• the first two chimeric antigen receptors (CAR) T-cell therapies in the European Union: Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) are both advanced therapy medicinal products (ATMPs) intended for the treatment of certain blood cancers. Kymriah and Yescarta were designated as orphan medicines during their development. They are also the first medicines supported through EMA’s PRIority MEdicines (PRIME) scheme to receive a positive opinion from the Committee.

• Inovelon
• Jinarc
• Lenvima
• Opdivo
• Rapamune

Together with the approval recommendation for the first CAR-T cell therapies, the Committee also recommended an extension to the therapeutic indication for RoActemra (tocilizumab) to include the treatment of CAR-T-cell-induced cytokine release syndrome (CRS), a known serious side effect of CAR-T cell therapies.

Four other orphan medicines were recommended for approval by the Committee:

• Cablivi (caplacizumab) for the treatment of acquired thrombotic thrombocytopenic purpura
• Mepsevii (vestronidase alfa) for the treatment of mucopolysaccharidosis type VII
• Veyvondi (vonicog alfa) for the treatment of von Willebrand disease
• Vyxeos (daunorubicin / cytarabine) for the treatment of acute myeloid leukaemia.

The COMP adopted 13 positive opinions recommending the following medicines for designation as orphan medicinal products to the European Commission, for:

• Treatment of hereditary angioedema
• Treatment of Duchenne muscular dystrophy
• Treatment in haematopoietic stem cell transplantation
• Treatment of neurodegeneration with brain iron accumulation
• Treatment of growth hormone deficiency
• Treatment of cystinuria
• Treatment of tuberculosis
• Treatment of perinatal asphyxia
• Treatment of ornithine transcarbamylase deficiency
• Treatment of Friedreich's ataxia
• Treatment of multiple osteochondromas,
• Treatment of mucopolysaccharidosis type I
• Treatment of pre-eclampsia

The COMP also recommended the amendment to 1 existing orphan designation:

• Interferon beta for treatment of acute respiratory distress syndrome (initially for treatment of acute lung injury).

LAMZEDE (velmanase alfa) is a medicine used for patients with mild to moderate alpha-mannosidosis. It is used for treating non-neurological effects.

This medicine was previously granted "orphan designation".

There were "exceptional circumstances" concerning the approval of this medicine. This happens when the applicant can show that they are unable to provide comprehensive data on the efficacy and safety of the medicine for which authorisation is being sought, due to the rarity of the condition it is intended for, limited scientific knowledge in the area concerned, or ethical considerations involved in the collection of such data.

Marketing authorisation date: 23/03/2018

Marketing authorisation holder: Chiesi Farmaceutici S.p.A

AMGLIDIA (glibenclamide) is a medicine used to treat newborns and children with neonatal diabetes, a form of diabetes that occurs in the first 6 months of life and that requires treatment with insulin. AMGLIDIA was shown to be effective in patients with whose disease was caused by certain genetic mutations.

Neonatal diabetes is rare, and AMGLIDIA was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 15 January 2016.

AMGLIDIA is a ‘hybrid medicine’. This means that it is similar to a ‘reference medicine’ containing the same active substance, but is available in a different formulation. While the reference medicine DAONIL is given as tablets, AMGLIDIA is available as a liquid (suspension).

Marketing authorisation holder: Ammtek

Marketing authorization date: 28/05/2018

PEMETREXED KRKA (pemetrexed) is a cancer medicine used to treat two types of lung cancer:

• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery
• advanced non-small-cell lung cancer of the kind known as “non-squamous”, where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received platinum-based chemotherapy

It is a “generic medicine”. This means that PEMETREXED KRKA contains the same active substance and works in the same way as a ‘reference medicine’ already authorised in the EU called ALIMTA.

Marketing authorisation holder: KRKA d.d.

Marketing authorisation date: 22/05/2018

The FDA approved the marketing of the following drugs with approved orphan indication:

• RUBRACA (rucaparib) for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. (04/06/2018; Clovis Oncology, Inc.)
• AFINITOR (everolimus) for the adjunctive treatment of adult and pediatric patients age 2 years and older with tuberous sclerosis complex (TSC)-associated partial-onset seizures. (04/10/2018; Novartis Pharmaceuticals Corp.)
• recombinant von Willebrand factor (rhVWF) is indicated for use in adults (age 18 and older) diagnosed with von Willebrand disease (VWD) for perioperative management of bleeding (04/13/2018; Baxalta US, Inc.)
• CRYSVITA (burosumab-twza) is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 1 year of age and older (04/17/2018; Ultragenyx Pharmaceutical, Inc.)
• TAVALISSE (fostamatinib disodium hexahydrate) is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. (04/17/2018; Rigel Pharmaceuticals, Inc.)
• TAGRISSO (osimertinib) is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test (04/18/2018; AstraZeneca Pharmaceuticals LP)
• JYNARQUE (tolvaptan) is indicated to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD) (04/23/2018; Otsuka Pharmaceuticals Co., Ltd.)
• MEKINIST (trametinib) is indicated, in combination with dabrafenib, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection (04/30/2018; Novartis Pharmaceuticals Corporation)
• TAFINLAR (dabrafenib) is indicated, in combination with trametinib, for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection (04/30/2018; Novartis Pharmaceuticals Corporation)

The FDA approved the marketing of the following drugs with approved orphan indication:

• RITUXAN(R) (rituximab) is indicated for the treatment of adult patients with moderate to severe pemphigus vulgaris (06/07/2018; Genentech, Inc.)
• VENCLEXTA (venetoclax) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) without 17p deletion, who have received at least one prior therapy (06/08/2018; AbbVie, Inc)
• KEYTRUDA (pembrolizumab) is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy (06/13/2018; Merck, Sharp & Dohme Corp.)
• AVASTIN (bevacizumab) is indicated in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, is indicated for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection. (06/13/2018; Genentech, Inc.)
• Moxidectin tablets are indicated for the treatment of onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older (06/13/2018; Medicines Development Limited)
• CINRYZE(R) (C1 esterase inhibitor (human)) is a C1 esterase inhibitor indicated for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (6 years old and above) with Hereditary Angioedema (HAE). (06/20/2018; Shire)
• ABLYSINOL (dehydrated alcohol) is indicated to induce controlled cardiac septal infarction to improve exercise capacity in adults with symptomatic hypertrophic obstructive cardiomyopathy who are not candidates for surgical myectomy. (06/21/2018; Belcher Pharmaceuticals, LLC)
• EPIDIOLEX (cannabidiol) is indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older. (06/25/2018; GW Pharma Ltd.)
• BRAVTOVI (encorafenib) is indicated, in combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test (06/27/2018; Array BioPharma, Inc.)
• MEKTOVI is indicated, in combination with encorafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test (06/27/2018; Array BioPharma, Inc.)
• SIGNIFOR (pasireotide) is indicated for the treatment of patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. (06/29/2018; Novartis Pharmaceuticals Corporation)