Two Years of PRIME Experience: EMA Grants Eligibility to 36 Medicines
With two years of experience under its belt with the PRIority MEdicines (PRIME) scheme, the European Medicines Agency (EMA) offered its perspective in a new report Monday on a program designed to offer additional support for biopharma sponsors developing products with promising preliminary clinical evidence and the potential to significantly address an unmet medical need.Of the 177 requests for eligibility to PRIME received and assessed since the scheme’s launch in March 2016, EMA says it has granted eligibility to 36 programs, 30 of which are for rare diseases and 19 of which are in oncology or hematology. Advanced therapy medicines also made up 40% of products granted eligibility.
“Two years on, the Agency has already received the first three marketing authorization applications for medicines that were accepted for PRIME,” EMA said. “They are all currently are under evaluation with the first opinion expected later in 2018.”
By comparison, many of the drugs granted eligibility in PRIME have also received breakthrough or orphan designations from the US Food and Drug Administration (FDA). And for at least one medicine granted PRIME eligibility, Novartis’ Kymriah (tisagenlecleucel), FDA is one step ahead of EMA and already approved the treatment last August.
Perspective
EMA said in Monday’s report that both the number of requests and the rate eligible/granted indicator have remained fairly constant and matched forecasts. With an average of eight requests received per month, EMA also said the quality of applications received is good and most eligibility requests received (161 out of 169) are at the proof of concept stage supported by exploratory data.
In terms of what additional support sponsors receive, PRIME products have received enhanced support from the agency, with so far: 31 kick-off meetings, followed by 37 scientific advice sessions (on 22 different products), with “many including input from multiple committees as well as other stakeholders (Health Technology Assessment (HTA) bodies, patients).”
Any sponsor engaged in the exploratory clinical trial phase of development can submit a request to enter the PRIME scheme, based on the availability of preliminary clinical evidence in patients indicating the promising activity of the medicinal product and its potential to significantly address an unmet medical need (proof of concept).
EMA also noted that smaller companies and academics can apply earlier to PRIME.
“While PRIME is open to all companies on the basis of preliminary clinical evidence (proof of concept), applicants from the academic sector and SMEs [small- and medium-sized enterprises] can apply earlier on the basis of compelling non-clinical data and tolerability data from initial clinical trials (proof of principle),” the agency said.
In the two years, EMA also said only eight requests were submitted by SMEs at the proof of principle stage.
“Out of these, three had been granted eligibility to PRIME at this early stage of development. Notably, the sponsor for one of these products has subsequently provided the Agency with exploratory data on its progress to proof of concept, enabling confirmation of PRIME eligibility,” the report said.
| Products Granted PRIME Eligibility | |||||
|---|---|---|---|---|---|
| Company | Name/Active Substance | Type | Indication | Supporting Data | FDA Breakthrough Therapy Designation |
| Albireo | A4250 | Chemical | Progressive Familial Intrahepatic Cholestasis | Nonclinical + Clinical exploratory | No |
| Spark Therapeutics/ Pfizer | PF-06838435/SPK-9001 | Advanced Therapy | Hemophilia B | Nonclinical + Clinical exploratory | Yes |
| Biomarin | BMN 270 | Advanced Therapy | Hemophilia A | Nonclinical + Clinical exploratory | Yes |
| uniQure | AMT-060. AMT-061 | Advanced Therapy | Hemophilia B | Nonclinical + Clinical exploratory | Yes |
| AveXis (acquired by Novartis) | AVXS-101 | Advanced Therapy | Pediatric patients diagnosed with spinal muscular atrophy Type 1 | Nonclinical + Clinical exploratory | Yes |
| MeiraGTx | AAV2/8-hCARp.hCNGB | Advanced Therapy | Achromatopsia associated with defects in CNGB3 | Nonclinical + Tolerability first in man | No (but did receive rare pediatric disease designation) |
| Biogen | Aducanumab | Biological | Alzheimer's Disease | Nonclinical + Clinical exploratory | No |
| Sage Therapeutics | Allopregnanolone (Brexanolone) | Chemical | Postpartum depression | Nonclinical + Clinical exploratory | Yes |
| Apogenix | Asunercept | Biological | Glioblastoma | Nonclinical + Clinical exploratory | No |
| BlueBird Bio | Autologous CD34+ haematopoietic stem cells transduced with lentiviral vector encoding the human βA-T87Q-globin gene (Lentiglobin) | Advanced Therapy | Beta-thalassaemia major | Nonclinical + Clinical exploratory | Yes |
| Adaptimmune | NY-ESO-1c259T | Advanced Therapy | Treatment of HLA-A*0201, HLA-A*0205, or HLA-A*0206 allele positive patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumour expresses the NY-ESO-1 tumour antigen | Nonclinical + Clinical exploratory | Yes |
| Juno Therapeutics (acquired by Celgene) | JCAR017 | Advanced Therapy | Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) | Nonclinical + Clinical exploratory | Yes |
| Celgene and Blubird Bio | bb2121 | Advanced Therapy | Relapsed and refractory multiple myeloma patients whose prior therapy included a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody | Nonclinical + Clinical exploratory | Yes |
| Novimmune | Emapalumab (NI-0501) | Biological | Primary haemophagocytic lymphohistiocytosis (HLH) | Nonclinical + Clinical exploratory | Yes |
| Ignyta | Entrectinib | Chemical | NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapy | Nonclinical + Clinical exploratory | Yes |
| Alnylam | Givosiran | Chemical | Prevention of acute attacks of hepatic porphyria | Nonclinical + Clinical exploratory | Yes |
| Edimer Pharmaceuticals | EMI 200 | Biological | Treatment of X-linked hypohidrotic ectodermal dysplasia | Nonclinical + Clinical exploratory | No but obtained Fast Track and orphan designations |
| GlaxoSmithKline | Humanized antibody targeting B cell maturation antigen conjugated with maleimidocaproyl monomethyl auristatin F (GSK2857916) | Biological | Multiple myeloma | Nonclinical + Clinical exploratory | Yes |
| Hansa Medical | Imlifidase | Biological | Prevention of graft rejection following solid organ transplantation | Nonclinical + Clinical exploratory | No but obtained orphan drug designation |
| Inotrem | LR12 (Motrem) | Chemical | Septic shock | Nonclinical + tolerability first in man | No |
| Alnynam | Lumasiran | Chemical | Primary Hyperoxaluria Type 1 | Nonclinical + Clinical exploratory | Yes |
| Sanofi | olipudase alfa | Biological | Non-neurological manifestations of acid sphingomyelinase deficiency | Nonclinical + Clinical exploratory | Yes |
| Roche | Polatuzumab vedotin | Biological | Relapsed and refractory patients with diffuse large B cell lymphoma | Clinical exploratory | Yes |
| Allergan | Rapastinel | Chemical | Major depressive disorder | Nonclinical + Clinical exploratory | Yes |
| Mereo BioPharma | BPS804 (Setrusumab) | Biological | Osteogenesis imperfecta types I, III and IV | Nonclinical + Clinical exploratory | No |
| ChemoCentryx | CCX168 (Avacopan) | Chemical | ANCA Associated Vasculitis | Nonclinical + Clinical exploratory | No but granted orphan designation |
| Kite Pharma | KTE-C19 | Advanced Therapy | Diffuse Large B-Cell Lymphoma | Nonclinical + Clinical Exploratory | Yes |
| Tocagen | Vocimagene amiretrorepvec | Advanced Therapy | High grade glioma | Nonclinical + Clinical Exploratory | Yes |
| Merck | Ebola Zaire Vaccine | Vaccine | Ebola Virus | Nonnclinical + Clinical Exploratory | Yes |
| CymaBay | MBX-8025 | Chemical | Primary Biliary Choloangitis | Nonclinical + Clinical Exploratory | No |
| MYR GmbH | Myrcludex B | Chemical | Treatment of chronic hepatitis D | Nonclinical + Clinical Exploratory | No |
| AtaraBio | ATA 129 | Advanced Therapy | Epstein-Barr Virus-associated Post Transplant Lymphoproliferative Disorder in the allogeneic hematopoietic cell transplant setting who have failed on rituximab. | Nonclinical + Clinical Exploratory | Yes |
| DNAtrix Therapeutics | DNX-2401 | Advanced Therapy | Treatment of recurrent glioblastoma in patients for which a gross total resection is not possible or advisable, or for those who refuse further surgery | Nonclinical + Clinical Exploratory | No but obtained Fast Track status |
| GBT | GBT440 (Voxelotor) | Chemical | Sickle Cell Disease | Nonclinical + Clinical Exploratory | No but it obtained Fast Track |