Slew Of New Drugs Accepted For EU Market Review, Three For Fast Track
Executive Summary
Four orphan drugs, Roche’s tissue agnostic cancer treatment entrectinib, and a single-dose oral vaccine for cholera are among the raft of new products that the European Medicines Agency has started to review for potential approval across the EU.
A total of 13 new investigational medicines have this month made it onto the list of products that the European Medicines Agency is reviewing for potential pan-EU marketing approval. Three of them have also secured an accelerated assessment.
Among the products that the EMA has accepted for review under its standard timetable are Roche’s tissue agnostic drug entrectinib, for treating certain solid tumors and lung cancer, Novartis’s breast cancer treatment alpelisib, Abbvie’s rheumatoid arthritis drug upadacitinib, and a single-dose oral cholera vaccine, Vaxchora, from Emergent BioSolutions.
The latest three products granted an accelerated assessment were among the four new orphan drugs to make it onto the list. They are Roche’s polatuzumab vedotin for treating relapsed and refractory patients with diffuse large B-cell lymphoma (DLBCL), Stemline Therapeutics’ Elzonris (tagraxofusp) for blastic plasmacytoid dendritic cell neoplasm (BPDCN), and Karyopharm’s relapsed or refractory multiple myeloma treatment selinexor.
The other new orphan drug, which is being reviewed under the standard timetable, is Agios’s Tibsovo (ivosidenib) for treating adult patients with relapsed or refractory acute myeloid leukemia with an IDH1 mutation.
The remaining five new entries on the list are all generics or biosimilars. They are diclofenamide (the therapeutic area is ophthalmological), two azacitidines (antineoplastic), cinacalcet (calcium homeostasis) and infliximab (immunosuppressant).
Obtaining Fast Track Can Be Tricky
Regarding the products granted an accelerated assessment, the EMA reserves this procedure for drugs it believes are of major interest for public health and are therapeutic innovations. The fast-track pathway can reduce the marketing authorization application (MAA) review timeframe from up to 210 days to 150 days (not counting clock stops in both cases). Companies may apply for an accelerated assessment, but they do not necessarily get it. (Also see "EU Accelerated Assessment Tracker: Nine Definites So Far From 24 Requests In 2018 " - Pink Sheet, 10 Jan, 2019.). To date, eight MAAs are being assessed under the pathway.
Roche is probably not surprised that polatuzumab vedotin was granted an accelerated assessment. The product had previously been accepted onto the PRIME scheme, the EMA’s priority medicines initiative for getting drugs for unmet medical need to patients faster. Sponsors of PRIME-designated products are offered early and enhanced dialogue with the EMA to help them generate better data and more robust evidence on their medicine’s benefits and risks, and they can expect to have their eventual MAA reviewed under the accelerated assessment procedure.
On the other hand, entrectinib, which has failed to secure an accelerated assessment, had also been accepted on PRIME, but matters here are somewhat complicated.
The fast-track request submitted by Roche for entrectinib was in relation to a single MAA covering two indications, one of which was covered by the PRIME designation: treatment of adult and pediatric patients with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive locally advanced or metastatic solid tumors, who have progressed following prior therapies, or as initial therapy when there are no acceptable standard therapies. The other indication was for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC).
Fast-track status was granted for the solid tumor indication but not, it appears, for NSCLC, which has in turn led to the overall request for accelerated assessment being turned down. The EMA has previously told the Pink Sheet that it considers the entire scope of a planned application and issues a single recommendation, either accepting or rejecting the request in its totality – accelerated assessment can only concern the entire scope of a single application for a marketing authorization.
Meanwhile, Roche has had better luck with securing fast-track status for entrectinib in the US. On Feb. 19, it said that the Food and Drug Administration had accepted its new drug applications for the product and had granted priority review for both indications. Under a priority review, the FDA aims to take action on an application within six months, compared with 10 months under standard review. The agency is expected to make a decision on approval by Aug. 18.
The FDA has also accepted Roche’s biologics license application and granted priority review for polatuzumab vedotin, the company said this month. Here the indication is for the use of polatuzumab vedotin in combination with bendamustine plus Roche's Rituxan (rituximab) for the treatment of patients with relapsed or refractory DLBCL. The agency is expected to make a decision on approval by Aug. 19.
FDA Concerns Over Selinexor
As for some of the other new products under review by the EMA, the Pink Sheet reported last week that the US regulators appear to have significant reservations about the clinical profile of Karyopharm’s selinexor, ahead of its Feb. 26 review of a new drug application (NDA) for use of the product in treating relapsed or refractory multiple myeloma. (Also see "Karyopharm’s Selinexor: US FDA Unconvinced By Efficacy In Single-Arm Trial" - Pink Sheet, 22 Feb, 2019.) According to a pre-meeting briefing document from the agency's Oncologic Drugs Advisory Committee, the NDA filing is based on a single-arm Phase II study (STORM) in fourth-line multiple myeloma and the FDA has concerns about the data. The committee will consider whether the approval should await results from the company's ongoing Phase III randomized trial (BOSTON).
Single-Dose Cholera Vaccine
Vaxchora is the cholera vaccine that Emergent BioSolutions acquired when it bought PaxVax in 2018.
“Europe is an important market for us,” Abbey Jenkins, senior vice-president and head of Emergent's Vaccines and Anti-Infectives Business Unit, told the Pink Sheet. “We have established European commercial operations as well as a distributor partner network that support the sales and marketing of our travelers vaccines including Vaxchora,” she said.
Jenkins noted that Vaxchora is the only vaccine available in the US for active immunization against cholera. “However, in Europe, there is a vaccine currently available for cholera, with an established market and recommendations for use," she noted.
Valneva's oral cholera vaccine Dukoral, which was approved in Europe in 2004, is given in two doses, one to six weeks apart. "Our plan is to bring Vaxchora, our single-dose cholera vaccine, to Europe,” Jenkins said.
The EMA's list of medicines under review for EU market approval was last compiled on Feb. 12.
From the editors of Scrip Regulatory Affairs.