The Committee for Medicinal Products for Human Use (CHMP) has recommended for marketing approval eight medicines, including PCSK9 inhibitor Repatha (evolocumab) and two immunotherapeutic medicines of a new class known as programmed cell death protein 1 (PD-1) inhibitors – Keytruda (pembrolizumab) and Nivolumab BMS (nivolumab).
IHS Life Sciences perspective | |
Significance | The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended for marketing authorisation approval in Europe eight medicines (including two generics) and six therapeutic indication extensions at its May meeting. |
Implications | The new medicines recommended for approval under the European Union's centralised procedure are Repatha (evolocumab), Keytruda (pembrolizumab), Nivolumab BMS (nivolumab), Unituxin (dinutiximab), Evotaz (atazanavir + cobicistat), Omidria (phenylephrine + ketorolac), and the two generics Bortezomib Accord (bortezomib) and Pregabalin Zentiva (pregabalin). |
Outlook | Following the positive recommendation by the CHMP, the European Commission is expected to issue its final decision – which in the vast majority of cases is in line with the CHMP's recommendation – within two months. Among the drugs recommended for approval are a PCSK9 inhibitor and two PD-1 inhibitors – two classes of drugs that are expected to boost substantially the burden on payors. |
At its May meeting, the European Medicines Agency's Committee of Medicinal Products for Human Use (CHMP) recommended for marketing authorisation eight medicines, comprising six originators and two generics. It also issued positive opinions for approval of six indication extensions. The committee did not issue negative recommendations for any medicines at this meeting, but it confirmed its previous recommendation to suspend the marketing authorisation of medicines for which EU approval was based primarily on clinical studies conducted at GVK Biosciences in Hyderabad, India. This decision is based on re-examination requested by marketing authorisation holders for seven of the medicines concerned. Separately, the CHMP reported that two applications for marketing authorisation were withdrawn, including one for Aripiprazole Mylan (aripiprazole) from Mylan and the other for Corluxin (mifepristone) from Corcept Therapeutics (both US).
The full text of the CHMP announcement regarding the May meeting decisions is available here.
CHMP's May decisions | ||
Drug | Company/organisation | Indication |
Positive recommendations for new originator drugs | ||
Evotaz (atazanavir + cobicistat) | Bristol-Myers Squibb (BMS, US) | Treatment of HIV-1-infected adults without known mutations associated with resistance to atazanavir. |
Keytruda (pembrolizumab) | Merck & Co (US) | Treatment of melanoma. |
Nivolumab BMS (nivolumab) | BMS | Treatment of adults with squamous non-small-cell lung cancer (NSCLC). |
Omidria (phenylephrine + ketorolac) | Omeros London Limited (UK) | Maintenance of intraoperative mydriasis, prevention of intraoperative miosis, and reduction of acute postoperative ocular pain in intraocular lens replacement surgery in adults. |
Repatha (evolocumab) | Amgen (US) | Hypercholesterolaemia, mixed dyslipidaemia, and homozygous familial hypercholesterolaemia. |
Unituxin (dinutuximab) | United Therapeutics (US) | Treatment of high-risk neuroblastoma. |
Positive recommendations for new generics | ||
Bortezomib Accord (bortezomib) | Accord Healthcare (UK) | Treatment of multiple myeloma. |
Pregabalin Zentiva (pregabalin) | Zentiva (part of Sanofi, France) | Treatment of epilepsy and generalised anxiety disorder. |
Positive recommendations for new therapeutic indications* | ||
Fycompa (perampanel) | Eisai (Japan) | Adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy. |
Impruvica (ibrutinib) | Janssen-Cilag (the European subsidiary of US pharma company Johnson & Johnson, J&J) | Treatment of adult patients with Waldenström's macroglobulinaemia (WM) who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy. |
Kuvan (sapropterin) | Merck KGaA (Germany) | Treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with phenylketonuria (PKU) who have been shown to be responsive to such treatment. |
Simponi (golimumab) | Janssen Biologics (subsidiary of J&J) | Treatment of adults with severe, active non-radiographic axial spondyloarthritis with objective signs of inflammation, as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response, or are intolerant, to non-steroidal anti-inflammatory drugs (NSAIDs). |
Stelara (ustekinumab) | Janssen-Cilag | Treatment of moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older, who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies. |
Xultophy (insulin degludec + liraglutide) | Novo Nordisk (Denmark) | Treatment of adults with type 2 diabetes mellitus to improve glycaemic control in combination with oral glucose-lowering medicinal products when these alone or combined with a GLP-1 receptor agonist or basal insulin do not provide adequate glycaemic control |
Source: CHMP | ||
Outlook and implications
The current round of CHMP decisions is particularly significant as it marks the recommendation for marketing approval of three different types of immunotherapeutics. Keytruda (pembrolizumab), to treat advanced (unresectable or metastatic) melanoma, Nivolumab BMS (nivolumab), to treat adults with squamous non-small-cell lung cancer (NSCLC), and Unituxin (dinutiximab), for the treatment of high-risk neuroblastoma – a type of cancer that most often occurs in young children. It is noteworthy that Unituxin was granted an orphan-drug designation in 2011. Cancer immunotherapies are treatments that use the body's own immune system to fight the disease – and Keytruda and Nivolumab BMS are part of a new class of cancer drugs known as PS-1 inhibitors. The therapeutic benefit potential of PD-1 inhibitors has been recognised by regulators, which have permitted them faster market access; for example, Keytruda was approved in the United States under the breakthrough-therapy designation procedure based on only Phase II results, while Japan became the first country in the world to approve nivolumab (under the Opdivo brand name; see United States: 5 September 2014: Merck's PD-1 inhibitor garners US FDA approval, BMS's nivolumab priced at premium in Japan). However, industry observers have been raising concerns about the burden on payors that PD-1 inhibitors are expected to exert. Notably, Keytruda was granted access to the UK market in March under the United Kingdom's Early Access to Medicines Scheme (EAMS) for the treatment of advanced melanoma – becoming the first drug to gain market access under the EAMS programme while awaiting completion of the CHMP's review (see United Kingdom: 11 March 2015: Merck & Co's Keytruda receives approval through early access scheme in UK).
Among the originator medicines that have been recommended for marketing authorisation, another highly significant decision is that for Repatha (evolocumab). It is a first-in-class treatment to lower high levels of cholesterol in the blood of people whose cholesterol is not controlled despite taking optimal doses of statins or who cannot take statins. Repatha is also recommended for the treatment of homozygous familial hypercholesterolaemia, a rare inherited disorder. It is the first monoclonal antibody in this therapeutic area and represents a new treatment option for patients who are unable to control their high cholesterol despite taking currently available therapies. Repatha is part of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor class of drugs.
If payors are concerned about the cost of PD-1 inhibitors, these worries pale in comparison with the fears regarding the potential cost of PCSK9 inhibitors. There is a risk that PCSK9 inhibitors could be taken not only by those whose cholesterol cannot be controlled by statins, but also by people who should be treated with statins. Repatha is intended for injection under the skin either once every two weeks or once a month, which could potentially increase convenience for some patients and would boost adherence to treatment compared with daily statin tablets. Given that the cost of PCSK9 inhibitors to the US healthcare system has been estimated at USD150 billion annually by CVS Health, payors are understandably concerned (see United States: 18 February 2015: CVS Health warns new PCSK9 inhibitor CVD drugs' costs will "eclipse" that of Sovaldi). European payors, in light of the austerity measures already in effect in some markets, are expected to pose significant reimbursement barriers to Repatha to ensure that its use is limited to the approved indications and off-label use is strongly discouraged.
The positive recommendation by the CHMP means that Europe could – depending on how quickly the European Commission issues final approval to Repatha – have the first PCSK9 inhibitor in the market before the US. The US Food and Drug Administration is still reviewing Repatha and another PCSK9 inhibitor – Praluent (alirocumab) from Regeneron (US).