New Therapeutic Targets & A Rich Year For Approvals: EMA’s PRIME In 2020
Executive Summary
Last year saw the number of applications accepted onto the European Medicines Agency’s priority medicines scheme inch up and the notoriously high rejection rate for applications drop.
A total of 20 investigational drugs secured a place on the European Medicines Agency’s PRIME (priority medicines) scheme in 2020, with some of them targeting new therapeutic areas and indications. The margin is small, but that’s the most that have been accepted in any year since the scheme began in 2016.
While the number of applications reviewed for entry onto the scheme was similar to that in the previous two years, the rejection rate – still at well over 50% – was the lowest ever.
2020 was also fruitful in terms of the number of PRIME-designated products that went on to win pan-EU marketing authorization.
The first treatment for non-alcoholic steatohepatitis (NASH) gained entry to the scheme last year. NASH, a common but serious liver disorder, is a potentially lucrative market that has been littered with late-stage failures.
PRIME designations were also finally granted for products targeting cardiovascular disease and pneumology-allergology – two therapeutic areas for which a raft of applications for a place on the scheme have failed to make the grade.
The 20 investigational therapies that made it on the scheme last year represent a third of the products that were considered for entry.
Nine medicines that had entered the scheme in previous years were approved in 2020, bringing to 13 the total number of PRIME-supported treatments that are now authorized for use across Europe.
PRIME was launched in 2016 with the aim of helping companies get promising medicines for unmet medical needs to patients faster.
Companies that make it onto the scheme are offered enhanced support from the EMA to help optimize their development plans and generate robust data. They can also expect that the eventual EU marketing application for their product will be eligible for review under the agency’s accelerated assessment mechanism. That said, fast-track is not a given and it is not uncommon for products that have come through PRIME to be reviewed under standard timelines.
2020 In Numbers
A total of 84* requests for a PRIME designation have been accepted since the scheme was launched around five years ago and 239 applications have been rejected. These figures, sourced from the EMA’s 2019 annual report and information the agency published this year, do not include the small number of applications that are submitted but not reviewed because they fall outside the scope of the scheme.
The 20 investigational therapies that made it on the scheme in 2020 covered a wide range of therapeutic areas (see Figure 1). As in previous years, many of them targeted cancer or a hematological disorder, and around a half were advanced therapy medicinal products (ATMPs).
The EMA reviewed 60 applications for entry onto the scheme in 2020. This is similar to the 57, 59 and 67 requests reviewed in 2019, 2018 and 2016 respectively, but lower than in 2017 when requests peaked at 81 following the launch of the scheme.
At 20, the number of requests accepted last year was slightly higher than in previous years – 16 were accepted in 2019, 14 in 2018, 19 in 2017 and 15 in 2016 (see Figure 2).
Applications Denied
In keeping with the norm, most of the applications considered in 2020 were rejected – 39 out of the 60 reviewed applications were denied, and one that was reviewed in October is still being considered by the EMA. (Also see "Winners And Losers: A Deep-Dive Into The EMA’s PRIME Scheme" - Pink Sheet, 17 Aug, 2020.)
Notably, the rejection rate last year was at its lowest – 65% compared with rejection rates ranging between around 72% and 78% in previous years.
PRIME has tough eligibility criteria. Applicants must convince the EMA that their investigational product has the potential to benefit patients with an unmet medical need, based on early clinical data – a requirement that most companies have found difficult to meet.
In the pneumology-allergology area, for example, 12 applications for PRIME designation have been denied, as have 16 requests for drugs targeting cardiovascular diseases.
The EMA has previously explained why applications fail to make the grade. (Also see "Why Four In Five Applications For PRIME Still Fail Two Years On: EMA Clarifies Expectations" - Pink Sheet, 11 May, 2018.) As noted by industry in the past, a great deal of preparation is required when it comes to putting together an application for entry to the scheme.
The fact that a medicine is not accepted in PRIME does not mean that its development should not be pursued. As previously noted by the agency, "medicines that are not granted PRIME access can still benefit patients by providing alternative treatment options for a disease."
Therapeutic Areas
The products accepted onto the scheme last year included five for oncology and three for hematology-hemostaseology, according to the therapeutic areas as categorized by the EMA.
There were two products each in the three areas of vaccines, cardiovascular diseases and endocrinology-gynecology-fertility-metabolism.
There was one each in the six areas of infectious diseases, neurology, ophthalmology, gastroenterology-hepatology, immunology-rheumatology-transplantation and pneumology-allergology.
To date, PRIME-designated products cover a range of therapeutic areas, with oncology and hematology medicines making up the largest share (see Figure 3).
All of the products accepted onto the scheme last year were based on nonclinical and clinical exploratory data.
Nine were ATMPs, seven were biologicals, three were chemicals (small molecules) and one was an immunological (see Figure 4).
PRIME First for NASH
Last year’s successful entries include efruxifermin (EFX), from Akero Therapeutics, which was granted a PRIME designation for NASH in October.
There are no authorized treatments for NASH in the major markets including the EU or US, although Cadila Healthcare received approval in India last year to market its diabetic dyslipidemia and hypertriglyceridemia drug saroglitazar as a treatment for NASH. Last year was supposed to see the first disease-specific drug finally be approved in the US for the liver disorder. Instead, 2020 was beset with late-stage failures. (Also see "The Top Five (Non-COVID) Pharma Stories Of 2020" - Scrip, 20 Jan, 2021.) (Also see "Zydus Cadila First Off The Block In NASH After India Approval" - Scrip, 6 Mar, 2020.)
According to Akero, the PRIME designation for its investigational FGF21 analog provided “important validation for the potential of EFX to become a foundational NASH monotherapy." It underscores “not only the high level of unmet need for therapeutics to treat this life-threatening disease, but also EFX's potential to address multiple aspects of NASH and its associated comorbidities,” the company said.
New Therapeutic Areas
Biologicals bentracimab and sotatercept, from PhaseBio Pharmaceuticals and Acceleron Pharma respectively, became the first cardiovascular disease medicines to enter the scheme. Bentracimab (PB2452) is for reversing the antiplatelet activity of ticagrelor in major bleeding and sotatercept is for treating pulmonary arterial hypertension.
Brensocatib, from Insmed, was the first product to enter PRIME’s pneumology-allergology category. Insmed was granted a PRIME designation for the small molecule in November, for the treatment of non-cystic fibrosis bronchiectasis.
Nine Marketing Approvals
The PRIME-designated products that won EU marketing approval last year were Blenrep, Rozlytrek, Tecartus, Givlaari, Hepcludex, Zolgensma, Idefirix, Oxlumo and Polivy. Zynteglo and Ervebo were approved in 2019, and Kymriah and Yescarta in 2018 (see Figure 5).
Other Notable New Entrants
Other new entrants to PRIME last year were VLA1553, a single-shot chikungunya vaccine candidate from Valneva, and VAC18193, Janssen Pharmaceuticals’ vaccine candidate for the prevention of lower respiratory tract disease caused by respiratory syncytial virus.
ECT-001, a cell therapy that ExCellThera is developing for use in urgent allogeneic hematopoietic stem cell transplants, was accepted onto the scheme last December. The designation for the ATMP was based on promising results from several Phase I/II clinical trials of the treatment for severe blood disorders. The company said the clinical trial data it was collecting were showing that ECT-001 “vastly reduces the incidence of severe complications and improves outcomes for patients who require blood stem cell transplants.”
Among the entries in November was lacutamab, in development by Innate Pharma for patients with relapsed or refractory Sézary syndrome who have received at least two prior systemic therapies. The first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody was the first potential treatment of any sub-type of T-cell lymphoma that had received a PRIME designation, the company noted.
Gene Therapies
A number of the new ATMPs accepted on the scheme last year were gene therapies.
Among these was AAV-RPGR, the first treatment in PRIME that targets x-linked retinitis pigmentosa, a severe disease that causes rapid progression to blindness and total loss of vision in most patients by the fourth decade. The treatment is being developed by MeiraGTx and Janssen.
LentiGlobin (bb1111), a gene therapy from bluebird bio, and CTX001, a gene-edited therapy from CRISPR Therapeutics/Vertex Pharmaceuticals, are both targeting sickle cell disease.
There is another potential treatment for sickle cell disease in PRIME. Oxbryta (voxelotor), from Global Blood Therapeutics, entered the scheme in 2017 and was accepted for review by the EMA for potential EU marketing approval just this month. A small molecule drug, Oxbryta is a first-in-class oral, once-daily therapy to treat hemolytic anemia in patients with sickle cell disease. It was approved in the US for sickle disease in November 2019. GBT noted that there are currently no approved therapies in Europe that have the potential to modify the course of the disease. It believes its product could be the first.
PRIME Versus US BTD
PRIME is similar to the breakthrough therapy designation (BTD) scheme that the US Food and Drug Administration operates. BTD is designed to expedite the development and review of drugs that are intended to treat a serious condition and for which preliminary clinical evidence indicates may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
A number of products on the PRIME scheme have also received BTD designation.
In 2019, the EMA published a report on a workshop it held with the FDA about their early access mechanisms such as PRIME and BTD. (Also see "Regulators, Industry Agree That Frequent Communication Is Key In Developing Breakthrough, PRIME Therapies " - Pink Sheet, 1 Aug, 2019.)
2021
The EMA decides whether to accept or reject applications for entry onto PRIME during the monthly meetings of its human medicines committee, the CHMP. The latest CHMP meeting took place on January 25-29. The agency will publish the decisions it made on new applications at this meeting shortly.
*Some documents from the European Medicines Agency say that 84 applications have been accepted onto the PRIME scheme while another says the number is 85.