DUBLIN – Although Europe has moved first to approve Blenrep (belantamab mafodotin), Glaxosmithkline plc’s antibody-drug conjugate (ADC) as a fifth-line therapy in relapsed or refractory multiple myeloma, U.S. patients may well be first to gain access to the new drug.
The EMA’s Committee for Human Medicinal Products (CHMP) voted July 24 in favor of its approval but owing to the European Commission’s standard delay of 67 days before putting a rubber stamp on the decision – which is intended to allow individual European Union member states to comment on pending authorizations – it will not receive formal approval until September. The FDA suffers no such impediment and could well approve the drug before then, following the recent unanimous vote in its favor by the agency’s Oncology Drugs Advisory Committee.
Blenrep, which comprises an antibody directed at B-cell maturation antigen conjugated to an auristatin F payload, will be the first ADC approved for myeloma and is in line to become the ninth ADC in total to reach the market. It is a graduate of the EMA’s Prime scheme for streamlining and accelerating the development and approval process for innovative drugs deemed to be of major public health importance. It is in line to receive conditional authorization, based on the open-label phase II Dreamm-2 study, in which patients attained an overall response rate of 32% and median overall survival of 13.7 months.
In all, the CHMP voted in favor of eight new drugs, as well as one biosimilar and two generics during its July meeting. The committee also voted against recommending two dossiers, those submitted by Swedish Orphan Biovitrum AB (Sobi) and by Stemline Therapeutics Inc., on behalf of Gamifant (emapalumab) and Elzonris (tagraxofusp), respectively, even though both drugs were previously approved by the FDA.
Sobi will file for re-examination of the Gamifant application. The drug is an antibody that binds to and neutralizes interferon-gamma, the main driver of primary hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening inflammatory condition. It had gained FDA approval in November 2018 for treating adults and children, but the CHMP ruled that the evidence presented in its favor – from a trial in 34 patients – did not conclusively prove that the drug was effective even though a number of patients exhibited responses and went on to receive bone marrow transplants. Sobi licensed the molecule from Novimmune SA, of Plan-les-Ouates, Switzerland, which now operates as Light Chain Bioscience.
For The Menarini Group, of Florence, Italy, the news on Elzonris, was not only bad – it was also late. The application – which was submitted in January 2019 by Stemline – was originally due to receive a fast track review but was switched to a standard review last year due to Brexit-related pressures on the EMA. The drug, a fusion protein comprising diphtheria toxin linked to interleukin-3, is in development for treating blastic plasmacytoid dendritic cell neoplasm, a rare, aggressive form of acute myeloid leukemia. Its U.S. approval and anticipated approval in Europe prompted a $677 million buyout of New-York-based Stemline in May, but the CHMP judged that the application was based on a poorly designed trial that recruited too few patients to demonstrate a favorable risk-benefit profile, given the drug’s risk of causing capillary leak syndrome.
The CHMP also voted through filgotinib, the would-be blockbuster JAK1 inhibitor developed by Galapagos NV and Gilead Sciences Inc., as a rheumatoid arthritis therapy, but, again, U.S. patients are likely to gain access first. The drug has an FDA PDUFA date of Aug. 19. Even before its approval, the drug has become a fabled part of the recent history of biopharma in Europe. It has transformed Mechelen, Belgium-based Galapagos into one of Europe’s bellwether biotechs, it helped to persuade Foster City, Calif.-based Gilead to put down about $5 billion in cash to get access to ex-European rights to the Galapagos pipeline, and it became something of a poster child for poor practice among some big pharma partners. Filgotinib will be sold as Jyseleca.
There was also good news for Basel, Switzerland-based Novartis AG, which gained a positive vote for Adakveo (crizanlizumab), a P-selectin blocker already approved in the U.S. for treating recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients. In the pivotal Sustain trial, it reduced the number of episodes per year by 45% as compared with placebo (median annual VOCs 1.63 vs. 2.98). It also reduced time spent in the hospital by 42%. What’s more, three times as many patients on drug as compared with placebo remained free of any VOC episode over a one-year study period.
The CHMP voted through two anti-infectives. The HIV preventive therapy Dapivirine Vaginal Ring, is recommended for approval under the Article 58 pathway, which is intended for drugs used in low and middle-income countries outside of the European Union. Developed by a partnership that includes the International Partnership for Microbicides, of Silver Spring, Md., and the U.S. National Institute of Allergy and Infectious Diseases, the therapy is aimed at women in sub-Saharan Africa who are unable to negotiate safe sex practices with male partners. It provides 28 days of locally delivered controlled-release drug. Insmed Inc., of Bridgewater, N.J. received a positive vote for Arikayce liposomal (amikacin) for treating non-tuberculosis lung infections caused by Mycobacterium avium complex in patients who do not have cystic fibrosis.
Two cancer drugs, both already approved by the FDA, also received positive votes. Cambridge, U.K.-based Astrazeneca plc is in line for an approval of its Bruton’s tyrosine kinase inhibitor, Calquence (acalabrutinib) in chronic lymphocytic leukemia. Blueprint Medicines Corp., of Cambridge, Mass., will gain approval for its Kit inhibitor, avapritinib, in unresectable or metastatic gastrointestinal stromal tumors that have the platelet-derived growth factor alpha D842V mutation. Confusingly, the drug will be marketed in Europe as Ayvakyt, whereas it is called Ayvakit in the U.S.
The CHMP also voted in favor of one pain drug, Zynrelef (bupivacaine/meloxicam), which San Diego-based Heron Therapeutics Inc. developed for postoperative pain. Its stance diverges sharply from that of the FDA, which recently slapped a second complete response letter on the file.