The Committee for Orphan Medicinal Products (COMP) has released the latest tranche of recommendations for new orphan drug designations in the European region. The list of positive opinions is one of the largest in recent years, and includes 33 new orphan drug recommendations.
Implications | COMP published recommendations for the inclusion of 33 medicinal products in the European registry of orphan medicines on 19 September. |
Outlook | COMP recommendations are subject to a final approval process by the European Commission; the commission is expected to publish decisions within 30 days of receiving details of the COMP recommendation. Inclusion on the European orphan drug registry marks a significant regulatory milestone for manufacturers, since it offers the potential to secure 10-year market exclusivity upon market-authorisation approval, as well as certain development incentives. |
The Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) has adopted 33 recommendations for inclusion in the European Union (EU) registry of orphan medicinal products for human use. The full COMP document was published on 19 September, and is available here.
Drug endorsements adopted at second session | Company / organisation | Indication |
|---|---|---|
2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-{4-[4-(5-fluoro-pyrimidin-2-yl)piperazin-1-yl]-phenyl}-2-oxo-acetamide | F2G (UK) | Invasive aspergillosis |
(6aR,10aR)-3-(1',1'-dimethylheptyl)-delta-8-tetrahydrocannabinol-9-carboxylic acid | TMC Pharma Services (UK) | Cystic fibrosis |
A non-covalent trimer of tumour necrosis factor fused to an antibody specific to the extra-domain B of fibronectin in single-chain variable fragment format | Philogen (Italy) | Soft-tissue sarcoma |
Autologous mononuclear cells derived from human cord blood | BrainRepair UG (haftungsbeschränkt) | Periventricular leukomalacia |
Autologous T-cells transduced with lentiviral vector containing a chimeric antigen receptor directed against CD19 | Novartis (Switzerland) | Diffuse large B-cell lymphoma |
E)-(6-((N-methyl-((3-methylbenzofuran-2-yl)methyl)amino)-3-oxoprop-1-en-1-yl)-2-oxo-3,4-dihydro-1,8-naphthyridin-1(2H)-yl)methyl phosphate, bis ethanolamine salt | Voisin Consulting (US) | Osteomyelitis, |
Human monoclonal IgG1 antibody against tissue factor pathway inhibitor | Pfizer (US) | Haemophilia A |
Lutetium-177(3+), S2,S7-cyclo[N-{4,7,10-tricarboxymethyl-1,4,7,10-tetraaza-cyclododecan-1-ylacetyl}-4-chloro-L-phenylalanyl-D-cysteinyl-4-[(4S)-2,6-dioxo-1,3-diazinane-4-carboxamido]-Lphenylalanyl-4-(carbamoylamino)-D-phenylalanyl-L-lysyl-L-threonyl-L-cysteinyl-D-tyrosinamide] | Ipsen Pharma (France) | Gastroenteropancreatic neuroendocrine tumours |
Mogamulizumab | Kyowa Kirin (Japan) | Cutaneous T-cell lymphoma |
N-[(2S)-5-{[(1R, 2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-methylpiperazin-1-yl)-1- oxopentan-2-yl]-4-(1H-1,2,3-triazol-1-yl) benzamide, bistosylate salt | Imago BioSciences (US) | Myelofibrosis |
Radio-iodinated anti-CD45 murine monoclonal antibody | Wainwright Associates (UK) | haematopoietic stem cell transplantation |
Synthetic 15-amino-acid macrocyclic peptide acylated with a polyethyleneglycol palmitoylated linker | Ra Europe (UK) | Paroxysmal nocturnal haemoglobinuria |
Venetoclax | AbbVie (US) | Multiple myeloma |
Venetoclax | AbbVie (US) | Diffuse large B-cell lymphoma |
Xenon | Neuroprotexeon (US) | Ischaemia reperfusion injury |
Source: Second COMP discussion (6–8 September 2016) | ||
In September, US-based pharmaceutical company Celgene published a report seeking to counter fears over the continued affordability of orphan drugs in the US market (see United States: 13 September 2016: Growth in US orphan drug spending to slow – report). The analysis of historical spending partners suggested "a slowing in the growth of orphan drug expenditures".
Drug endorsements adopted at first session | Company / organisation | Indication |
|---|---|---|
Acebutolol hydrochloride | Therapicon (Italy) | Smith-Magenis syndrome |
Adeno-associated viral vector serotype 5 containing the human RLBP1 gene | Horama SAS (France) | Retinitis pigmentosa |
Adeno-associated viral vector serotype 2/2 containing a gene encoding the channelrhodopsin-2 protein | Alacrita LLP (UK) | Retinitis pigmentosa |
Autologous mononuclear cells derived from human cord blood | BrainRepair UG (haftungsbeschränkt) | Neonatal encephalopathy |
Carbamazepine for treatment of metaphyseal chondrodysplasia | University of Newcastle upon Tyne (UK) | Schmid type |
Chemically modified human recombinant sulfamidase | SOBI (Sweden) | Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) |
Crenolanib besylate | Arog Pharmaceuticals (US) | Soft-tissue sarcoma |
Crenolanib besylate | Arog Pharmaceuticals (US) | Acute myeloid leukaemia |
Exendin (9-39) | Eiger Biopharmaceuticals (US) | Noninsulinoma pancreatogenous hypoglycaemia syndrome |
Fenretinide | Clinipace (Germany) | Peripheral T-cell lymphoma |
Haematopoietic stem cells modified with a lentiviral vector containing the CD18 gene | Centro de Investigación Biomédica en Red (Spain) | Leukocyte adhesion deficiency type I |
Melatonin | Therapicon (Italy) | Smith-Magenis syndrome |
P-ethoxy growth factor receptor-bound protein 2 antisense oligonucleotide | Clinical Network Services (UK) | Acute myeloid leukaemia |
Recombinant adeno-associated viral vector encoding a human micro-dystrophin gene under the control of a muscle specific promoter | Pharma Gateway (Sweden) | Duchenne muscular dystrophy |
Self-complementary adeno-associated viral vector serotype 9 containing the SGSH gene | Ser-mes Planificación (Spain) | Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome) |
Tadekinig alfa | Coté Orphan (UK) | Haemophagocytic lymphohistiocytosis |
Tetrofosmin | ProActina (Greece) | Diagnosis of glioma |
Ubiquinol | Centro de Investigación Biomédica en Red (Spain) | Primary coenzyme Q10 deficiency syndrome |
Outlook and implications
COMP adopted 33 recommendations for orphan drug designations at its 181 plenary meeting held in September, of which 18 were decided during the first COMP discussion, and 15 at the second. Among the decisions were notable positive recommendations for US firm Arog Pharmaceuticals' crenolanib besylate, a type I pan-FLT3 inhibitor, for indications in both soft-tissue sarcoma (STC) and acute myeloid leukaemia (AML); the company's leading product candidate has potential best-in-class properties, according to Arog. Crenolanib besylate is currently being investigated as a potential treatment option for AML, as well as gastrointestinal stromal tumours (GIST), glioma, and non-small cell lung cancer (NSCLC). An open-label Phase II label study (RO-004) of crenolanib besylate is planned to enrol patients with relapsed/refractory AML with FLT3-activating mutation.
Elsewhere, US-based company AbbVie's venetoclax was recommended for orphan drug status in the indications of multiple myeloma and diffuse large B-cell lymphoma. Venclexta (venetoclax) is being developed by AbbVie and Roche (Switzerland), with the two companies co-promoting the drug in the United States; however, AbbVie holds commercialisation rights in other countries. The B-cell lymphoma protein (Bcl-2) family inhibitor was recently added by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to its Early Access to Medicines Scheme (EAMS) for chronic lymphocytic leukaemia (CLL). The 2016 EAMS classification essentially allows UK patients to access the drug before EMA market authorisation is finalised.
In July 2016, AbbVie announced the initiation of a Phase III trial (ABT-199) of Venclexta in patients with relapsed or refractory multiple myeloma. The randomised, double-blind, placebo-controlled trial will investigate the efficacy and safety of an oral version of Venclexta – in combination with the proteasome inhibitor bortezomib and corticosteroid dexamethasone – in about 240 patients who are considered sensitive or naïve to proteasome inhibitors and have received one to three prior lines of therapy for multiple myeloma. The primary endpoint of the trial is set as progression-free survival, while secondary outcome measures include overall survival, objective response rates, and the duration of response. The estimated completion date for the Phase III study is late 2019; Phase II studies (CAVALLI and ROMULUS) of Venclexta and Rituxan in DLBCL have been initiated, and are expected to publish results in 2019.
In April 2016 the US FDA announced the approval of Venclexta tablets for patients with chronic lymphocytic leukaemia (CLL) with 17p deletion who have received at least one prior therapy. AbbVie is planning to develop venetoclax in combination with Imbruvica as a potential best-in-class treatment for CLL (see United States: 13 April 2016: US FDA approves AbbVie's and Roche's venetoclax for rare form of leukaemia). Looking ahead, AbbVie's strategy is to develop the drug in other CLL settings, in addition to DLBCL and multiple myeloma, which if successful would significantly expand the commercial potential of the drug. For AbbVie, the orphan drug designation is also important given that this is the first oncology drug that the company has developed internally.
The final decision to grant orphan designation is taken by the European Commission. Nevertheless, COMP recommendations are a positive step for the applicant companies since, once approved, the drugs will be entitled to a 10-year period of patent protection in the EU, as well as other incentives during the development process. This is dependent on market authorisation subsequently being granted in the relevant indication; the period of potential market exclusivity can also be extended by a further two years in the case of paediatric medicine approvals. The European Commission is expected to reach a final decision on awarding orphan drug status within 30 days of the recommendations.
Orphan drug designations are reserved for candidate productions indicated in life-threatening or serious conditions that affect fewer than five in 10,000 of the population in the EU.