Clovis Confident, Portola Not: CHMP Decides On EU Marketing Applications
Executive Summary
Eight EU marketing authorization applications are up for an opinion this week from the CHMP, the European Medicines Agency committee that recommends whether or not products should be approved.
Clovis Oncology is hoping to be proved right in its assumption that the positive feedback the European Medicines Agency recently conferred on its investigational ovarian cancer drug Rubraca (rucaparib) will this week translate into a formal recommendation for EU market approval.
Rubraca, which has orphan drug status, is one of eight products that the EMA’s human medicines committee, the CHMP, is this week deliberating on whether or not to recommend for approval. Clovis last month said that its marketing authorization application (MAA) for rucaparib had secured a positive trend vote from the CHMP, meaning that a positive recommendation for approval is likely to be on the cards.
The other MAAs up for an opinion from the CHMP include those for Portola Pharmaceuticals’ Factor Xa inhibitor Bevyxxa (betrixaban), which - in contrast to Rubraca - has previously received a negative trend vote, and Radius Health’s osteoporosis drug Tymlos (abaloparatide), which has struggled to reach this stage. In addition, the CHMP is expected to adopt opinions on ViiV Healthcare and Janssen Pharmaceutical’ fixed-dose combination HIV treatment dolutegravir/rilpivirine, two biosimilars – trastuzumab and infliximab – and two generics – pemetrexed and prasugrel.
The CHMP’s latest monthly meeting is taking place on March 19-22. The committee’s opinions will be announced on March 23 and forwarded to the European Commission for a binding decision. The CHMP may choose to issue a positive or a negative opinion or it can withhold an opinion if it still has questions about an application.
Initial Applications
More details about each of the drugs up for a CHMP opinion are provided in the bullets below.
- Rubraca is a monotherapy for the treatment of a limited population of advanced ovarian cancer patients with deleterious BRCA mutation (germline and/or somatic). If the Clovis product receives a positive opinion from the CHMP, it could become the third PARP inhibitor approved in Europe for patients with ovarian cancer, competing with rivals AstraZeneca and Tesaro. The company announced on Feb. 21, that the CHMP had “communicated a positive trend vote" for the rucaparib MAA, originally submitted during the fourth quarter of 2016. This vote would have come as a relief to the company given that the committee chose not to issue an opinion on the drug at its December 2017 meeting – indeed the CHMP has had four lists of outstanding issues (LoOIs) relating to the product – adopted on Feb, 23, 2018 and in September, November and December last year. [LoOIs can be adopted at the 180-day point in the 210-day-long evaluation procedure (day 120 for products being evaluated under the accelerated assessment mechanism) where the CHMP still has concerns about an application. More than 90% of MAAs have a day 180 LoOI.] (Also see "Think Positive: Clovis Confident Of CHMP Okay For Rubraca" - Scrip, 22 Feb, 2018.) In the US, the Food and Drug Administration approved Rubraca in 2016 as a monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for drug. The FDA has since accepted the company’s supplemental new drug application for rucaparib for a second line or later maintenance treatment indication in ovarian cancer. The application has been granted priority review status with a Prescription Drug User Fee Act date of April 6, 2018.
- Bevyxxa is for the prevention of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness with risk factors for VTE. Portola said last month that the CHMP had communicated a negative trend vote for the drug, meaning the CHMP is unlikely to adopt a positive opinion this week. The company said that additional steps were likely to be needed to gain marketing approval in Europe. The CHMP’s position was that betrixaban efficacy was acknowledged in the Portola’s APEX trial, but uncertainties remained regarding a positive benefit risk. (Also see "EU Delays For Portola As CHMP Trend Votes Go Good And Bad " - Scrip, 22 Feb, 2018.) Betrixaban was approved by the US FDA in June 2017.
- Tymlos, for the treatment of osteoporosis, has struggled to get to the CHMP opinion stage. The CHMP has had three sets of outstanding issues on the MAA for abaloparatide – in December 2016 and in July and December 2017. It seems that the EMA’s concerns are mainly with the following of clinical trial protocols at a few key sites in Radius’s ACTIVE trial. (Also see "Orphans Dominate Products Seeking End-Of-Year Joy From CHMP" - Pink Sheet, 13 Dec, 2017.) Radius was due to appear before the CHMP on March 20 to provide an oral explanation in response to questions raised by the committee. The product was approved in the US in 2017.
- Dolutegravir/rilpivirine, for the treatment of HIV infection, is a fixed-dose combination of ViiV Healthcare’s integrase strand transfer inhibitor Tivicay (dolutegravir) and Janssen Pharmaceuticals’ non-nucleoside reverse transcriptase inhibitor Edurant (rilpivirine). The product was approved as Juluca in the US in November 2017 following a priority review. It was the first complete, single-pill, two-drug regimen approved by the FDA for HIV.
(Also see "Keeping Track: Flurry Of Approvals Rolls Over Into Holiday Season" - Pink Sheet, 1 Dec, 2017.) - Trastuzumab – another biosimilar version of Roche’s blockbuster breast and gastric cancer therapy Herceptin. As of March 5, three marketing applications for trastuzumab were under review at the EMA.
- Infliximab – a biosimilar of Johnson & Johnson's Remicade – is for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, psoriasis and ulcerative colitis. As of March 5, it was the only infliximab biosimilar under review at the EMA. It is likely to be Sandoz’s product, which was filed with the agency in May 2017 after the company acquired the European rights from Pfizer. The US firm gained FDA approval for the drug as Ixifi in December last year.
- Pemetrexed is for the treatment of malignant pleural mesothelioma and non-small cell lung cancer. This is likely to be a generic version of Eli Lilly's Alimta, which was approved in the EU in September 2004. Several other generics are already approved for these indications in the EU, including products from Sandoz, Accord, Actavis and Hospira (Pfizer).
- Prasugrel is for the prevention of atherothrombotic events. This is likely to be a generic version of Lilly/Daiichi Sankyo Europe’s Efient, which was authorized in the EU in February 2009. No opinion was give on this product last month.
Re-examinations
As expected, Puma Biotechnology requested a re-examination of the negative opinion the CHMP issued last month relating to the company’s potential new breast cancer treatment, Nerlynx (neratinib). (Also see "Five Drugs Set For EU Approval, Including Two Orphans " - Pink Sheet, 26 Feb, 2018.) Among other things, the CHMP this week is due to agree the appointment of re-examination rapporteurs and adopt a draft timetable for the re-examination.
Action is also expected on the CHMP's re-examination of the negative opinion from December 2017 on Pharma Mar's potential multiple myeloma treatment, Aplidin (plitidepsin). The company was due to appear before the committee to answer questions on March 21. (Also see "Decision Time At CHMP: Portola and Aegerion In Spotlight" - Pink Sheet, 21 Feb, 2018.)
Indication Extension Requests/Pfizer’s Sutent
The CHMP is also due to consider – either for an opinion or a request for supplementary information – therapeutic indication extension requests (Type II variations) relating to ten products.
The products in question are: Amgen’s Blincyto (blinatumomab) and Repatha (evolocumab); UCB Pharma's Briviact (brivaracetam) and Cimzia (certolizumab pegol); Ipsen’s Cabometyx (cabozantinib); Janssen-Cilag’s Darzalex (daratumumab); [MSD]’s Ivemend (fosaprepitant);
Vertex Pharmaceuticals’ Kalydeco (ivacaftor); GSK’s Nucala (mepolizumab); and Novartis Europharm’s Tyverb (lapatinib).
The CHMP last month turned down Pfizer’s request to extend the therapeutic indication of Sutent (sunitinib) to include adjuvant treatment of patients at high risk of recurrent renal cell carcinoma following nephrectomy. (Also see "Pfizer's Mylotarg Finally Gets CHMP Nod But No New Indication For Sutent" - Scrip, 26 Feb, 2018.) Pfizer has requested a re-examination of the negative opinion and the CHMP is due to adopt a timetable for the review at this month’s meeting.
Keytruda
Merck Sharp & Dohme is listed in the CHMP’s meeting agenda as possibly giving a post-authorization procedure oral explanation in relation to Keytruda (pembrolizumab) for the treatment of melanoma.
MSD declined to provide additional details but issued the following statement: “MSD works with global health authorities on a regular basis to understand data associated with our ongoing clinical trials. The oral explanation currently listed on the March 21 agenda has been cancelled but as always, we remain committed to working closely with the EMA to bring forward new treatment options for patients across multiple tumor types.”
AB Science's Masitinib
A fourth company was scheduled to provide an oral explanation over the course of the meeting – AB Science, which is seeking initial approval of its orphan drug masitinib, for the treatment of amyotrophic lateral sclerosis. AB Science was due to answer questions on March 21. An opinion is not expected at this stage.
From the editors of Scrip Regulatory Affairs.