2020 Sees Sharp Rise In EU New Drug Approvals

The number of new drugs containing new active substances approved in the EU rose significantly in 2020, underpinned by a strong showing for orphan-designated products and a string of novel medicines for cancer and infectious diseases. Notable among the new clutch of approvals was the first ever COVID-19 vaccine, Pfizer/BioNTech's Comirnaty.

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The EU approved a range of novel drugs last year

In 2020, 42 products containing a total of 41 new active substances received an EU marketing authorization, a sharp increase on the 28 NAS-containing products that were cleared in 2019, and just short of the three-year peak of 45 seen in 2018.

Among the most high-profile products to be approved last year were Pfizer Inc./BioNTech SE’s Comirnaty, the first vaccine for COVID-19, and Gilead Sciences, Inc.’s Veklury (remdesivir) for the treatment of COVID-19 in adults and adolescents with pneumonia requiring supplemental oxygen.

The year saw a host of other novel NAS-containing medicines OKd for pan-EU marketing, including three gene therapy products and a range of drugs for various cancer indications. A total of 17 orphan medicines were approved, well up on the five seen in 2019 and the same number as in 2018.

Several products containing known active substances gained approvals for orphan indications last year, while a number of other products with known substances, including novel combinations, also cleared the regulatory hurdle.

The number of products gaining an EU conditional marketing authorization rose to 12, from seven the previous year. They included both the COVID-19 products, Cominarty and Veklury, as well as the TB Alliance’s Dovprela (pretomanid), for highly drug-resistant forms of pulmonary tuberculosis, and Roche’s tumor-agnostic cancer drug Rozlytrek.

Three of the approvals were granted under the EU's "exceptional circumstances” mechanism: the two components of Janssen Pharmaceutica Inc.’s Ebola vaccine, and an orphan drug for anthrax inhalation, obiltoxaximab, from Elusys Therapeutics, Inc.

The New Approvals In 2020

The three gene therapy products approved last year all had orphan status.

Orchard Therapeutics Limited’s Libmeldy (autologous CD34+ cell enriched population that contains hematopoietic stem and progenitor cells transduced ex vivo using a lentiviral vector encoding the human arylsulfatase A gene) was cleared for the treatment of metachromatic leukodystrophy. This disease is an inherited neurometabolic disorder that causes progressive destruction of the white matter of the brain.

The other two gene therapies received a conditional marketing authorization. Kite Pharma, Inc.’s Tecartus (autologous anti-CD19-transduced CD3+ cells) was approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, and Novartis Gene Therapies (formerly AveXis) received approval for Zolgensma (onasemnogene abeparvovec), for treating patients with 5q spinal muscular atrophy.*

Oncology

Among the oncology drugs to get EU clearance last year was GlaxoSmithKline plc’s orphan drug Blenrep (belantamab mafodotin), a first-in-class humanized anti-BCMA treatment, which received a conditional approval for relapsed and refractory multiple melanoma. This is the first anti-BCMA therapy to be approved in the EU, according to the company.

Roche’s Rozlytrek (entrectinib), a tumor-agnostic TRK inhibitor, was conditionally approved for treating patients from 12 years of age with solid tumors with an NTRK gene fusion who have no satisfactory treatment options. It was also approved for adults with ROS1-positive, advanced non-small cell lung cancer not previously treated with ROS1 inhibitors.

Another product given a conditional authorization was Blueprint Medicines Corporation’s Ayvakyt (avapritinib), an orphan drug for treating adult patients with unresectable or metastatic gastrointestinal stromal tumors harboring the PDGFRA D842V mutation.

Novartis AG’s Piqray (alpelisib) was approved in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy.

Sanofi’s Sarclisa (isatuximab) is for treating adults with relapsed and refractory multiple myeloma, in combination with pomalidomide and dexamethasone. Sanofi said the drug was designed to induce programmed tumor cell death and immunomodulatory activity.

Pfizer’s orphan medicine Daurismo (glasdegib), in combination with low-dose cytarabine, was OKd for the treatment of newly diagnosed de novo or secondary acute myeloid leukemia in adults who are not candidates for standard induction chemotherapy.

Calquence (acalabrutinib), from AstraZeneca PLC, is indicated, as monotherapy or in combination with obinutuzumab, for the treatment of adult patients with previously untreated chronic lymphocytic leukemia (CLL). As monotherapy it is also indicated for adult CLL patients who have received at least one prior therapy.

Roche’s Polivy (polatuzumab vedotin), in combination with bendamustine plus rituximab, has a conditional approval as an orphan drug for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for a hematopoietic stem cell transplant.

Bayer AG’s Nubeqa (darolutamide) is for the treatment of adult men with non-metastatic castration resistant prostate cancer who are at high risk of developing metastatic disease.

Five New Vaccines

The most high-profile of the five vaccines approved last year was of course Pfizer/BioNTech’s Comirnaty for COVID-19 disease, which received a conditional marketing authorization on 21 December. The European Medicines Agency described the product as a “single-stranded, 5’-capped messenger RNA produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2.”

Another significant arrival last year was Janssen’s Ebola vaccine, which is composed of two individual vaccine elements, Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo), each of which has its own marketing authorization. Zabdeno is given first, with Mvabea being administered around eight weeks later as a booster.

The Ebola vaccine was approved under exceptional circumstances because Janssen showed that it was not possible to conduct a randomized controlled study to generate comprehensive data. The company must provide the EMA with an update on the collection of effectiveness data on an annual basis.

A cholera vaccine, Vaxchora, from Emergent BioSolutions, Inc., was approved for active immunization against disease caused by Vibrio cholerae serogroup O1 in adults and children aged six years and older.

The fifth vaccine was Supemtek, Sanofi Pasteur’s quadrivalent influenza vaccine (recombinant, prepared in cell culture).

The other new COVID-19 product authorized in the EU last year was Gilead’s Veklury for the treatment of COVID-19 in adults and adolescents aged 12 years and older with body weight at least 40kg with pneumonia requiring supplemental oxygen. As with Comirnaty, this was a conditional approval.

 

Infectious Disease Treatments

The infectious diseases area also saw the arrival of an important new treatment for patients with highly drug-resistant TB infections. The TB Alliance’s Dovprela (pretomanid) was authorized as an orphan medicine as part of a three-drug, six month, all-oral regimen for the treatment of adults with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive. 

Elusys Therapeutics’ orphan drug obiltoxaximab (called Anthim in the US and Canada) was authorized for use in combination with appropriate antibacterial drugs for the treatment and post-exposure prophylaxis of inhalational anthrax due to Bacillus anthracis when alternative therapies are inappropriate or unavailable. This was an exceptional circumstances approval because it was not possible to obtain complete information about obiltoxaximab because of the rarity of the disease and for ethical reasons.

German firm MYR GmbH received conditional approval for Hepcludex (bulevirtide), an orphan drug for chronic hepatitis delta virus infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease.

Xenleta (lefamulin), from Nabriva Therapeutics plc., is for the treatment of community-acquired pneumonia (CAP) in adults when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of CAP or when these have failed.

Shionogi & Co. Ltd.'s Fetcroja (cefiderocol sulfate tosilate) and Merck & Co., Inc.’s Recarbrio (imipenem/cilastatin/relebactam) were both OKd for the treatment of infections due to aerobic Gram-negative organisms in adults with limited treatment options. Relebactam is the NAS in Recarbrio.

Vocabria (cabotegravir), from ViiV Healthcare, is for the treatment of HIV infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with, agents of the non-nucleoside reverse transcriptase inhibitor and integrase inhibitor class.

Cardiovascular Disease

In the area of cardiovascular therapeutics, 2020 saw the approval of Novartis’s first-in-class small interfering RNA (siRNA) cholesterol lowering treatment, Leqvio (inclisiran), for the treatment of adults with primary hypercholesterolemia or mixed dyslipidemia. “Using a novel mechanism of action, the treatment has been shown to deliver effective and sustained LDL cholesterol reduction in patients with atherosclerotic cardiovascular disease,” the company said.

Esperion Therapeutics, Inc. received approval for two products for primary hypercholesterolemia or mixed dyslipidemia: Nilemdo (bempedoic acid) and Nustendi (bempedoic acid/ezetimibe).

Nilemdo is used in combination with a statin, with or without other fat-lowering medicines, in patients whose cholesterol levels are not lowered enough by the maximum dose of a statin. Nilemdo can also be used alone or in combination with other fat-lowering medicines in patients who cannot take statins.

Nustendi is used in combination with a statin in patients whose cholesterol levels are not lowered enough by the maximum dose of a statin taken together with ezetimibe. It can also be used alone in patients who cannot take statins and whose cholesterol levels are not lowered enough by ezetimibe.

Other Therapeutic Areas

Novartis received a conditional approval for its orphan drug Adakveo (crizanlizumab), for preventing recurrent vaso-occlusive crises in patients with sickle cell disease aged 16 years and older. The product can be given as an add on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.

Vertex Pharmaceuticals’ Kaftrio (elexacaftor/tezacaftor/ivacaftor) became the first triple combination product for cystic fibrosis in patients aged 12 years and up who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or heterozygous for F508del in the CFTR gene with a minimal function (MF) mutation. The EMA said the orphan treatment was “expected to provide a new therapeutic option for many cystic fibrosis patients, including those with MF mutations where no treatment exists.” Elexacaftor is the NAS in the combination.

Celgene Corporation received EU approval for Reblozyl (luspatercept) for transfusion-dependent anemia in adults with myelodysplastic syndromes or beta thalassemia. The orphan-designated product is a recombinant fusion protein consisting of a modified form of the extracellular domain of human activin receptor IIB linked to the human IgG1 Fc domain.

Givlaari (givosiran) is Alnylam Pharmaceuticals Inc.’s orphan treatment for acute hepatic porphyria in adults and adolescents aged 12 years and older.

Recordati SpA’s Isturisa (osilodrostat) was approved for endogenous Cushing’s syndrome in adults, an orphan indication.

The following products were also approved last year:

• Two new drugs for multiple sclerosis:  Celgene’s Zeposia (ozanimod), for adults with relapsing remitting multiple sclerosis, and Novartis’s Mayzent (siponimod) for adults with secondary progressive multiple sclerosis.

• Jyseleca (filgotinib), from Gilead/Galapagos, for moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti rheumatic drugs. Jyseleca may be used as monotherapy or in combination with methotrexate.

• Pfizer’s Staquis (crisaborole) for mild to moderate atopic dermatitis in adult and pediatric patients from two years of age with ≤ 40% body surface area affected by the condition.

• Beovu (brolucizumab), from Novartis, for the treatment of wet age-related macular degeneration in adults.

• Jazz Pharmaceuticals plc’s Sunosi (solriamfetol) to improve wakefulness and reduce excessive daytime sleepiness (EDS) in adults with narcolepsy (with or without cataplexy), and in those with obstructive sleep apnea whose EDS has not been satisfactorily treated with primary obstructive sleep apnea therapy such as continuous positive airway pressure.

• Tavlesse (fostamatinib), Rigel Pharmaceuticals, Inc.’s therapy for chronic immune thrombocytopenia in adults refractory to other treatments.

• Oxlumo (lumasiran), an orphan medicine from Alnylam to treat primary hyperoxaluria type 1 in all age groups.

• Idefirix (imlifidase), Hansa Biopharma AB’s orphan drug for the desensitization treatment of highly sensitized adult kidney transplant patients. This was the first approved drug for Hansa Biopharma, which said it would “bring hope to the thousands of highly sensitized patients across Europe waiting for a life-saving kidney transplant.”

* This article was amended on 21 January to reflect the fact that AveXis became Novartis Gene Therapies in September 2020.