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New EU products in 2014: a batch of breakthroughs, a bevy of anticancers and a troupe of orphans

This article was originally published in Scrip

Executive Summary

  • Clinuvel's groundbreaking drug Scenesse approved for phototoxicity
  • Holoclar becomes the first cell therapy to be OKd by the CHMP
  • New products for difficult-to-treat cancers
  • 14 orphan drug approvals
  • Five new drugs for hepatitis C
  • Three biosimilars including insulin

34 new active substances/biologics were among the 80-odd products approved for marketing by the European Commission in 2014, many of them for rare or difficult to treat diseases. Ten of the new products were biologics, the remainder being new chemical entities.

An analysis of the commission's online approvals database shows that nine of the new drugs were for cancer indications, four for hepatitis C and three for diabetes. Among the most high-profile approvals were Clinuvel's groundbreaking phototoxicity drug Scenesse (afemelanotide), PTC Therapeutics' Translarna (ataluren) for Duchenne muscular dystrophy and Gilead Sciences' Sovaldi (sofosbuvir) for hepatitis C.

The commission also issued marketing authorizations for a range of other products, including biosimilars, generics, combinations of new and/or existing substances, and radiopharmaceuticals. 14 of the therapies granted marketing authorization last year were orphan drugs, some of them containing older substances for new uses.

Orphan drugs also figured strongly among the positive opinions delivered by the European Medicines Agency's scientific committee, the CHMP. It recommended a total of 82 products for marketing authorization, a record 17 of them for rare diseases. Most of the products OKd by the committee went on to receive approval from the commission, although some of those recommended towards the end of the year are still in the approval queue, and one was withdrawn before it reached the marketing authorization stage.

Three firsts

Scenesse, which was approved under exceptional circumstances as an orphan drug on 22 December following a CHMP positive opinion in October, represents a big step forward on a number of fronts. This is the product's first approval worldwide, and it is the first ever treatment developed for the prevention of toxicity associated with the rare disorder erythropoietic protoporphyria, the most severe form of intolerance to sunlight and indoor light. It also stood out as the first drug to go through a new EMA pilot program whereby patients are involved more closely in the evaluation of new drugs by taking part in benefit-risk discussions at the CHMP.

Another novel orphan product for a rare disease, PTC Therapeutics' Translarna (ataluren), was approved for Duchenne muscular dystrophy. It is the first therapy to work by targeting the underlying causes of DMD, a rare progressive muscle disorder. However, it had a rough passage through the evaluation process: it was OKd only after the company submitted further analysis of the clinical data following an initial rejection by the CHMP.

2014 saw another breakthrough: the first positive opinion for a stem cell therapy. Chiesi's Holoclar for limbal stem cell deficiency due to ocular burns, a condition that affects about 3.3 out of 100,000 people in the EU and can eventually lead to blindness, was recommended for approval in December on the basis of an assessment by the EMA's Committee on Advanced Therapies (CAT). It has both orphan drug and advanced therapy designation and is now awaiting a final commission decision, which if all goes well should be forthcoming in a couple of months.

All three products followed special regulatory pathways: conditional marketing authorization for Translarna and Holoclar, and approval under exceptional circumstances for Scenesse. These mechanisms are used to speed up market access for medicines that fulfil unmet needs but lack comprehensive data at the time they are submitted for approval.

Orphans, cancer and hepatitis C

Some older substances were approved as orphan medicines for new indications, including ASK Pharmaceuticals' Kolbam (cholic acid) for inborn errors in primary bile acid synthesis, and Ketoconazole HRA from HRA Pharma for endogenous Cushing's syndrome (the product has been used for this condition for more than 30 years but has never been approved for this use and is often prescribed off-label).

Not all of the orphan products OKd by the CHMP made it all the way. In a case that showed that promising early data may not always support an early approval, Endocyte's Vynfinit (vintafolide) and its two companion diagnostic medicines Folcepri (etarfolatide) and Neocepri (folic acid) were withdrawn by the sponsor before the commission could issue a marketing authorization. The products, which had been recommended for conditional approval in ovarian cancer based on Phase IIb data, were pulled following the failure of the Phase III PROCEED trial.

Of the nine oncology therapies approved for marketing in 2014, a number were for difficult-to-treat cancers, including Janssen-Cilag's Imbruvica (ibrutinib) for relapsed/refractory mantle cell lymphoma/chronic lymphocytic leukemia (CLL), Roche's Gazyvaro (obinutuzumab) for CLL, Lilly's Cyramza (ramucirumab) for advanced stomach cancer, and AstraZeneca's Lynparza (olaparib) for maintenance therapy in ovarian/peritoneal/fallopian tube cancer responsive to platinum-based chemotherapy. All of these have orphan status.

Four novel products were approved for that notoriously tough condition, hepatitis C: Gilead's Sovaldi (sofosbuvir) and Harvoni (a combination of sofosbuvir and another NCE, ledipasvir), Bristol-Myers Squibb's Daklinza (daclatasvir) and Janssen-Cilag's Olysio (simeprevir). The CHMP's November positive opinion on a fifth treatment, AbbVie's oral, short-course, interferon-free treatment combination, Viekirax (ombitasvir/paritaprevir/ritonavir) plus Exviera (dasabuvir tablets), was converted into an EU approval in mid-January 2015.

With the hepatitis C field now sporting a variety of novel and effective products, some lively price competition can be expected, particularly as AbbVie seeks to compete with the Gilead drugs. It also raises the bar for new entrants, as outlined in a recent Datamonitor analysis (, 20 January 2015).

The diabetes area saw three new approvals: two in the fast-growing GLP-1 receptor agonist class, GSK's Eperzan (albiglutide) and Lilly's Trulicity (dulaglutide), and Boehringer Ingelheim's SGLT2 inhibitor Jardiance (empagliflozin).

In the respiratory field, GSK's new product for COPD, umeclidium bromide, was approved both as a single agent (Incruse) and in combination with another recent arrival, vilanterol trifenatate (which itself was first authorized in combination with fluticasone in November 2013), as Anoro (see below).


Among the three biosimilars authorized last year was Lilly's Abasria (insulin glargine) for diabetes. As the first biosimilar insulin to receive approval in Europe, Abasria will compete for marketing space against Sanofi's established blockbuster Lantus. The other two – Accord Healthcare's Accofil (filgrastim) and Finox Biotech's Bemfola (follitropin alfa) – contain substances that are already marketed as biosimilar products.

The number of biosimilars approved in the EU has now reached 20, containing a total of six substances (somatropin, filgrastim, follitropin alfa, epoetin, infliximab and insulin glargine). The next candidate could well be an etanercept product: Samsung Bioepis' version of Amgen's TNF inhibitor Enbrel is currently under evaluation at the CHMP.

New combinations

Some combinations of new and existing products were approved for marketing last year, including for diabetes, HIV and respiratory conditions:

  • Type 2 diabetes: Janssen-Cilag's Vokanamet (canagliflozin/metformin), Novo Nordisk's Xultophy (insulin degludec/liraglutide), and AstraZeneca's Xigduo (dapagliflozin/metformin).
  • HIV infection: ViiV Healthcare's Triumeq (dolutegravir/abacavir/lamivudine) (dolutegravir was also approved as a single agent) and Janssen-Cilag's Rezolsta (darunavir/cobicistat).
  • COPD: GSK's Anoro/Laventair (umeclidinium bromide/vilanterol trifenatate) and Almirall's Duaklir Genuair/Brimica Genuair (aclidinium bromide + formoterol dihydrate).
  • Oestrogen deficiency in post-menopausal women: Pfizer's Duavive (conjugated estrogens/bazedoxifene).

In an interesting example of a familiar drug being reformulated for a new use, Pierre Fabre's Hemangiol (propranolol) became the first product to be approved for the treatment of proliferating infantile hemangioma, and only the second ever to receive an EU pediatric-use marketing authorization (PUMA) – a freestanding approval reserved for new pediatric uses of older drugs that are no longer under patent protection.

82 positive CHMP opinions

The EMA's scientific committee, the CHMP, delivered 82 positive opinions in 2014, on a range of medicines: 40 new non-orphan substances, 17 orphan drugs, 21 generic/hybrid/informed consent products, three biosimilars and one pediatric-use product.

These included four orphans that were recommended in November/December and have now received or are likely to have a commission decision within the next couple of months: Holoclar, Sanofi's Cerdelga (eliglustat) for Gaucher disease (now approved), Boehringer Ingelheim's Ofev (nintedanib) for idiopathic pulmonary fibrosis (now approved), and Aptalis Pharma's Quinsair (levofloxacin hydrate) for lung infections in cystic fibrosis.

While the positive opinion tally did not quite match the number seen in 2011 (87), it continues a general upward trend in positive opinions since 2010, when there were 51. In 2013 there were 81.

The success rate of products evaluated by the CHMP also seems to be on the rise. The committee rejected just three products last year, compared with five in 2013 and eight in 2012, while the number of applications withdrawn before the CHMP opinion declined to seven, compared with eight, 10 and 13 in the three previous years.

The EMA said that overall, the number of medicines containing new active substances continues to increase, with one in two medicines recommended for approval containing a substance that has never been used in medicines before, and either targeting diseases for which no treatments were previously available or bringing added benefit over existing therapies.

Accelerated assessment

Seven products (including four hepatitis C drugs) were given the green light by the CHMP under the accelerated assessment procedure: Daklinza, Harvoni, Exviera, Viekirax, Ofev, Ketoconazole HRA, and Janssen-Cilag's Sylvant (siltuximab) for Castleman's disease. The EMA said the committee used accelerated assessment to "make a new generation of medicines available to patients potentially more quickly", noting in particular that the hepatitis drugs have "recently reshaped the way patients with chronic HCV infection can be treated".

The agency added that it provided more scientific support last year, with almost seven out of ten applicants receiving scientific advice from the CHMP, a figure that rose to four out of five where innovative medicines were involved. "This is a significant increase compared with 2013 when only half of applicants who had a positive opinion for their medicine had received scientific advice," it declared.

New chemical entities/biologics approved in EU in 2014*




Adempas (riociguat)

chronic thromboembolic pulmonary hypertension

Bayer Pharma

Cometriq (cabozantinib)

Advanced thryroid cancer

TMC Pharma Services

Cyramza (ramucirumab)

Gastric cancer


Daklinza (daclatasvir)

Hepatitis C

Bristol-Myers Squibb

Deltyba (delamanid)


Otsuka Pharmaceutical

Entyvio (vedolizumab)

ulcerative colitis/Crohn's disease


Eperzan (albiglutide)

Type 2 diabetes


Gazyvaro (obinutuzumab)

Chronic lymphocytic leukemia (CLL)


Harvoni (ledipasvir/sofosbuvir)**

Hepatitis C

Gilead Sciences

Imbruvica (ibrutinib)

relapsed/refractory mantle cell lymphoma/CLL


Incruse (umeclidinium bromide)



Jardiance (empagliflozin)


Boehringer Ingelheim

Latuda (lurasidone)



Lymphoseek (tilmanocept)

Radiopharmaceutical for cancer diagnosis

Navidea Biopharmaceuticals

Lynparza (olaparib)

Ovarian/peritoneal/fallopian tube cancer


Mekinist (trametinib)

Advanced melanoma with BRAF V600 mutation


Moventig (naloxegol)

Opioid-induced constipation


Neuraceq (florbetaben)

Radiopharmaceutical for diagnosis of AD/other cognitive impairment

Piramal Imaging

Nuwiq (simoctocog alfa)

Hemophilia A


Olysio (simeprevir)

Hepatitis C


Plegridy (peginterferon beta-1a)

Relapsing-remitting MS

Biogen Idec

Rixubris (nonacog gamma)

Hemophilia B


Scenesse (afamelanotide)

Prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP)


Sirturo (bedaquiline)



Sovaldi (sofosbuvir)

Hepatitis C

Gliead Sciences

Sylvant (siltuximab)

Castleman's disease


Tivicay (dolutegravir)

HIV infection

ViiV Healthcare

Translarna (ataluren)

Duchenne muscular dystrophy

PTC Therapeutics

Trulicity (dulaglutide)

Type 2 diabetes


Vargatef (nintedanib)

Non-small cell lung cancer

Boehringer Ingelheim

Velphoro (polynuclear iron)

Phosphorus control in adult chronic kidney disease

Vifor Fresenius

Vimizin (elosulfase alfa)


BioMarin Europe

Vizamyl (flutemetamol)

Radiopharmaceutical for diagnosing AD/other cognitive impairment

GE Healthcare

Zydelig (idelalisib)


Gilead Sciences

*Data taken from the European Commission's approvals database; **both sofosbuvir and ledipasvir are NCEs.



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