Although in 2020 health agencies worldwide were mostly focused in managing the COVID-19 public health emergency, EMA recommended 97 medicines for marketing authorisation. That’s not just a number. It’s a considerable amount of new treatment options for patients suffering from a variety of medical conditions throughout the European Union which also set precedents for all Healthcare Regulatory Agencies across the globe. EMA assessment of safety and efficacy based on clinical trials for these new drug therapies provide the foundation for the postmarketing surveillance. In this sense, EMA and the EU Member States continuously monitor its quality and perform risk-benefit asessment, taking regulatory actions when applicable; building the “Real World Evidence”, which is meaningful data for updated healthcare decisions. Measures may include a change to the product information and its corresponding package insert, the suspension or withdrawal of any treatment or indication, or a recall.

In the following lines, we will examine the approvals and highlight the most remarkable ones, which offer a new and innovative treatment for previously unmet medical needs.

39 out of the 97 drugs receiving a positive opinion during 2020 are new active substances, which means that were never authorized before as a medicinal product. Therefore, a 40% of the newly approved drugs significantly differ in properties with regard to safety and efficacy from other chemical substances previously authorised by EMA.

In fact, it is striking how these new drugs cover a broad range of therapeutic areas including:

Cancer

11 new drugs were approved for the treatment of diverse types of cancer including 3 drugs for HER2-positive breast cancer -Enhertu, Phesgo and Tukysa-; one for lung and thyroid cancer -Retsevmo-; one for acute myeloid leukaemia (AML) -Daurismo-; and one for prostate cancer -Nubeqa-.

In this group, there were noteworthy approvals for rare cancers, comprising a drug for gastrointestinal stromal tumour (GIST) -Ayvakyt-; 2 drugs for multiple myeloma -Blenrep and Sarclisa-, a tumour agnostic therapy for tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion -Rozlytrek- and the first and only CAR-T treatment for mantle cell lymphoma -Tecartus-.

Dermatology

A new drug -Staquis- was approved for atopic dermatitis in adults and children.

Endocrinology

Givlaari is the newly approved drug to treat acute hepatic porphyria (AHP) in adults.

Haematology/ Haemostaseology

Adakveo approved for sickle cell disease’s painful crises in patients aged 16 years and older. Calquence, approved for chronic lymphocytic leukaemia in adults. Elzonris approved for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults. Inrebic, approved for myelofibrosis in adults who have enlarged spleen. Lumoxiti approved for hairy cell leukaemia in adults.

Infections & Vaccines

A variety of infective diseases were covered with the 2020 EMA approvals; Hepatitis D (HDV), Anthrax, Tuberculosis, HIV-1, community-acquired pneumonia, influenza -one vaccine and one new drug-, 2 Ebola vaccines, a Cholera vaccine; and least but not last, one vaccine and one new drug for COVID-19.

Immunology/Rheumatology/ Transplantation

Idefirix, approved to enable kidney transplantation in highly sensitized patients.

Jyseleca, approved for adults with moderate to severe rheumatoid arthritis (RA).

Metabolism

Two new treatments –Nilemdo and Nustendi- for lowering cholesterol levels in adults.

Neurology

Two new drugs for treating rare, inherited, degenerative and life-threatening disorders in children: Libmeldy, for metachromatic leukodystrophy (MLD) and Zolgensma, a gene therapy medicine for spinal muscular atrophy (SMA).

Pneumology/Allergology

Kaftrio, to treat cystic fibrosis in adults and children aged 12 years and above.

Uro-nephrology

Oxlumo, To treat hyperoxaluria type 1 in adults and children.

Interestingly, 18 out of the 39 approved new active substances are used to treat rare diseases. According to EMA, a disease is considered rare if fewer than five in 10,000 people have it. Around 30 million people in the European Union (EU) suffer from a debilitating rare disease, which means one in 17 people; so finding effective treatments for these rare diseases is a huge challenge.

In this sense, the EMA encourages the development of orphan medicines for these rare -and in some cases neglected diseases-, understanding that these medicines have the potential to significatively benefit patients for which there are no other approved treatments.

In addition, as around 70% of rare diseases are genetic, their first symptoms develop during childhood. Therefore, through the 2020 data we can conclude that 39% of the new active substances approved for rare diseases are used to treat children.

This brings under the spotlight the fact that 12 out of the 30 new approvals that may apply to children are indicated in pediatric population. This is great news, as years ago, most of the pediatric drug use was ‘off-label’ because appropriate pediatric studies had not been conducted so the drugs had not been labelled by the EMA for ‘use in children’. Taking into account that children are a unique population with distinct developmental and physiological differences from adults, this ‘off-label’ use throughout the years sometimes led to inadequate dosing and lack of safety information which placed children at risk for adverse events and denied them potential therapeutic benefits.

Thankfully, over the last years multiple clinical trials on pediatric population have been conducted and today we can see the rewarding results: several children undergoing critical diseases -whether rare, genetic or disabling- have now a treatment option to improve their quality of life -which is proved to be safe and effective for them-.

Following with all the approvals for 2020 -and putting the new active substances aside- there were 83 recommendations on extensions of therapeutic indications. This is a substantial amount of indications; as the extension of the use of a medicine that is already authorised for marketing in the EU can also offer new treatment opportunities for patients -and is also a way for pharmaceutical companies to achieve the maximum profitability of their compound throughout its lifecycle-.

Finally, the approvals for new routes of administration or new pharmaceutical forms followed a different direction to the mentioned prolific approvals along 2020. Only four new routes of administration or new pharmaceutical forms for already marketed drugs were approved in the past year. These include Entyvio -subcutaneous vedolizumab for the treatment of ulcerative colitis and Crohn’s disease-, Darzalex – subcutaneous daratumumab for multiple myeloma -, Plegridy -Peginterferon Beta-1ª intramuscular injection for multiple sclerosis-, and also Suboxone -a sublingual film containing buprenorphine and naloxone for opioid-dependent patients-.

This shows that the development of targeted dosing regimens is still a challenge for the pharmaceutical industry; even more in the case of transdermal formulation development, for which we can appreciate no new transdermal patches have been approved over the last five years. In fact, the last two patches’ approvals by the EMA occurred both in 2015; comprising the contraceptive Lisvy patch -containing low doses of ethinylestradiol and gestodene in a small, round and transparent patch-; and Qutenza -a cutaneous patch containing capsaicin 8%, initially approved in 2009 for the treatment of peripheral neuropathic pain in non-diabetic adults which was granted a label extension in 2015 to include the treatment of adult diabetic patients with peripheral neuropathic pain.

Since novel pharmaceutical forms might collaborate in patients quality of life, by increasing patient adherence to therapy, ensure a proper dose is administered and improve quality of life for patients on long-term treatment, it is clear for us in Amarin that transdermal patches are the “stars” that fulfil these attributes in several ways:

• Improving the administration of well-known molecules in a non-invasive, pain-free, self-application manner.
• Avoiding the frequent dosing administration, providing a controlled and sustained drug release for defined time periods -involving a lower peak plasma concentration compared to oral forms-.
• Reducing side effects through avoiding both the gastrointestinal tract -minimizing local irritative effects- and the first-pass metabolism -safer in hepato-compromised patients-.
• Increasing the target patient population, as it can be administered to a patient who is sleeping, unresponsive, or unable to swallow oral medications.

In Amarin, we strongly believe in all the advantages the transdermal delivery systems have to offer for patients and their caregivers. This is why over the past 30 years we specialize in the development and manufacturing of patent-protected innovative formulations of well-known drugs and generic versions of transdermal and topical brand products.

The fact that no new transdermal systems were approved over the last five years confirms the transdermal patch development and manufacturing is a complex and long-term challenge, from formulation to manufacturing, therefore being a niche market on which only experienced players are in.

…And Amarin is proud to be part of them.

References:

• https://www.ema.europa.eu/en/medicines
• European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP). CHMP post-authorisation summary of positive opinion for Qutenza
• https://www.ema.europa.eu/en/news/human-medicines-highlights-2020