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Press Releases

Take a look at a selection of our recent media coverage:

Colchicine receives FDA approval for cardiovascular disease

22nd June 2023

Colchicine has become the first anti-inflammatory agent to be approved by the US Food and Drug Administration (FDA) for the treatment of cardiovascular disease (CVD).

According to the Europe-based manufacturer, Agepha Pharma, the FDA has approved colchicine 0.5 mg as the first anti-inflammatory athero-protective cardiovascular treatment, for patients either with established CVD or with multiple risk factors for the disease.

While both inflammation and hypercholesterolaemia jointly contribute to atherothrombotic disease, an analysis published in The Lancet in 2023, found that in patients receiving statins, inflammation was a stronger predictor for risk of future cardiovascular events and death than cholesterol. Colchicine achieves a beneficial effect in CVD at the cellular level through several mechanisms that include inhibition of endothelial cell dysfunction and inflammation, smooth muscle cell proliferation and migration, macrophage chemotaxis, migration, adhesion and platelet activation. 

Colchicine in patients with CVD

Evidence that colchicine is effective in CVD comes from a large study published in the New England Journal of Medicine. Over 5,000 patients with chronic coronary disease were randomised to colchicine 0.5 mg daily or matching placebo. The primary endpoint for the trial was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischaemic stroke or ischaemia-driven coronary revascularisation.

After a median of 28.6 months, significantly fewer patients assigned to colchicine experienced a primary endpoint event (hazard ratio, HR = 0.69, 95% CI 0.57 – 0.83, p < 0.001). Other work has also revealed how colchicine is effective in patients with chronic coronary disease both prior to and following an acute coronary syndrome.

Commenting on the approval, Paul Ridker, a consultant for Agepha Pharma as well as professor of medicine at Harvard Medical School and director of the Centre for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, said: ‘Approval by the FDA of the first drug to target cardiovascular inflammation is an important step forward for the care of our patients.

‘To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke.

Colchicine is formulated as a once-daily, continuous-use oral treatment for adults that can be used safely either alone or in combination with standard-of-care lipid-lowering medications to effectively reduce the risk of heart attack and stroke.

The manufacturer anticipates that it will be available for prescription in the US in the second half of 2023. Potential plans for gaining approval in the UK or EU are currently unknown.

Hope for dystrophic epidermolysis bullosa sufferers after gene therapy approval

15th June 2023

Dystrophic epidermolysis bullosa is caused by a gene mutation, and the recent FDA approval of the corrective gene therapy VYJUVEK represents the first specific treatment to become available. Rod Tucker finds out more.

Dystrophic epidermolysis bullosa (DEB) is a rare genetic, blistering skin disorder that is usually present from birth. In addition to blistering, open wounds develop together with extra-cutaneous manifestations, affecting the eyes, oral cavity and many internal organ systems. Moreover, the disease places a huge burden on sufferers, caregivers and their families.

DEB occurs as a result of mutations in COL7A1, a gene encoding the alpha-1 chain of collagen type VII (C7) which form the anchoring fibrils of the skin and mucous membranes. Individuals with the disease have been referred to as ‘butterfly children’ due to the mechanical fragility of their skin which is analogous to that of a butterfly’s wings.

The FDA approval of VYJUVEK – also known as beremagene geperpavec or B-VEC – provides the first novel topical gene therapy. The treatment contains two copies of the COL7A1 coding sequence, encapsulated in a modified herpes simplex virus (HSV) type 1.

The delivery of the functional genes within B-VEC is achieved after outer shell viral proteins interact with proteins on the surface of skin cells to facilitate viral nucleocapsid entry. Once within the cell, the viral DNA is transcribed and translated into C7 and secreted into the extracellular space to assemble into anchoring fibrils.

Although yet to be officially approved by the European Medicines Agency (EMA), in 2018 the organisation granted B-VEC orphan drug designation, which will hopefully simplify the approval process. In addition, the UK’s National Institute for Health and Care Excellence is currently appraising the treatment.

But how effective is this novel topical therapy?

Efficacy of B-VEC in DEB

In an abstract abstract presented at the World Congress on Epidermolysis Bullosa in 2020, researchers described the use of B-VEC applied the wounds of two patients with recessive DEB in a phase 1 trial. It also detailed the findings of a phase 2 trial in which a total of 10 patients received the treatment. Overall, seven out of eight wounds treated with B-VEC closed completely within a median of 20.14 days.

Based on these early and positive findings, a phase 3, randomised, double-blind, placebo-controlled trial was initiated and published in the New England Journal of Medicine. The trial enrolled 31 patients, including children and adults, with DEB.

The trial used an intra-patient control design in which for each patient, the site investigator selected two wounds of similar size, anatomical region, and appearance. The wounds within each pair were then randomly assigned in a 1:1 ratio to receive either a weekly application of B-VEC or placebo for 26 weeks. The primary endpoint was complete wound healing at six months, whereas a secondary endpoint was complete wound healing after three months.

The results were remarkable. After six months, 67% of wounds treated with B-VEC were completely healed, compared to 22% of placebo-treated wounds (p = 0.002). Furthermore, complete healing of wounds after only three months occurred in 71% of those using B-VEC and 20% of placebo-treated wounds (p < 0.001). The researchers also examined the durability of the wound response in terms of sustained complete healing at both three and six months. This was seen in 50% of wounds treated with B-VEC but only 7% of placebo-treated wounds.

These positive findings in the phase 3 trial formed the basis of the FDA approval. But the results were important for a number of other reasons. Firstly, the successful use of a topical gene therapy over time bode well for not just DEB, but potentially for other genetic skin disorders. Secondly, the trial demonstrated the successful use a replication-defective HSV vector.

Thirdly, since B-VEC is formulated as a methylcellulose gel, it enables the patient or carer to apply the product themselves to existing wounds. Finally, because patients with epidermolysis bullosa are at an increased risk of squamous cell carcinoma (SCC), which can develop within chronic wounds, B-VEC may ultimately lower the risk of SCC.

Other potential treatments

But B-VEC is not the only therapeutic modality under investigation and there at least three other approaches being trialled. The first involves tautologous keratinocyte sheets containing full-length C7 using a retroviral vector and transplanted onto wound sites. In a phase 1/2 trial using this technique, researchers observed how wound healing exceeding 50% occurred in 95% of treated wounds compared to 0% in untreated control wounds.

The second approach makes use of recombinant human collagen 7 replacement therapy, which is given intravenously. Results from a phase 2 open-label study showed that after 120 days, 69.2% of treated wounds achieved a pre-specified response of a >2-point improvement on a wound-specific assessment scale.

For the third approach, work with topical or intra-dermal gentamicin was seen to induce type VII collagen and anchoring fibril production at the dermal-epidermal junction of erosion sites in five patients with recessive dystrophic epidermolysis bullosa.

While the findings to date are promising, B-VEC is not a panacea. For instance, because the treatment does not penetrate through the skin, it is only able to treat existing wounds rather than preventing new ones from forming. Furthermore, it is likely to require life-long dosing and has no effect on the systemic disease manifestations.

The EMA estimates that epidermolysis bullosa affects up to 36,000 people across Europe and, despite its limitations, B-VEC has the potential to provide relief for the cutaneous symptoms of this burdensome disease, which will be welcomed by sufferers and carers alike.

Trofinetide approved for Rett Syndrome from two years of age

15th March 2023

Trofinetide is approved for treatment of the rare, neuro-developmental disorder Rett Syndrome in patients from two years of age

Acadia Pharmaceuticals has announced that it has received approval for trofinetide as a treatment for adult and paediatric patients with Rett Syndrome from two years of age.

Rett syndrome is described as a neuro-developmental disorder characterised by typical early growth and development followed by a slowing of that development, loss of functional use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.

The condition primarily affects females resulting in severe cognitive and physical disabilities and is estimated to affect about 1 in 12,000 girls and is only rarely seen in boys. Virtually all patients with Rett syndrome have one of > 300 distinct loss-of-function mutations in the MECP2 gene on the X chromosome, which encodes methyl-CpG binding protein-2, an essential transcriptional regulator in the brain required for normal neurodevelopment.

Before trofinetide, which is given orally, there were no recognised treatments for Rett syndrome and the drug is believed to work by normalising aberrant neural function resulting from MECP2 mutations. In an exploratory phase 2, multicentre, double-blind, placebo-controlled, dose-escalation study, trofinetide was found to provide a clinically meaningful improvement for patients with the syndrome. The approval by the FDA was based on the findings from LAVENDER, a phase 3 study of trofinetide for Rett syndrome.

The LAVENDER study evaluated the efficacy and safety of trofinetide compared to placebo in 187 female patients with Rett syndrome, five to 20 years of age. In the study, treatment with trofinetide produced a statistically significant improvement (compared to placebo) on both co-primary efficacy endpoints, measured by the change from baseline, in Rett Syndrome Behaviour Questionnaire (RSBQ) total score (p = 0.018), which is a caregiver assessment on a range of disease symptoms, and the Clinical Global Impression-Improvement (CGI-I) scale score (p = 0.003) at week 12, which represents a physician-based assessment. In the study, the most common side effects were diarrhoea (82%) and vomiting (29%).

The drug is likely to be available in the US from April 2023 although no information on its release elsewhere is yet known.

Zavegepant nasal spray approved for acute migraine

Zavegepant has become the first calcitonin gene-related peptide receptor antagonist nasal spray approved for the treatment of acute migraine.

Pfizer has announced that zavegepant has become the first calcitonin gene-related peptide receptor antagonist nasal spray to receive approval by the FDA for the management of acute migraine.

According to a study using data from 2016, it was estimated that globally, migraine affects some 1.04 billion people and caused 45·1 million years of life lived with disability. Although there was a breakthrough in treatment of migraine during the early 1990’s with the introduction of triptans, it later emerged that the calcitonin-gene-related peptide (CGRP) pathway was important in the pathophysiology of migraine.

While first generation drugs targeting this pathway, known as ‘gepants’ were effective, hepatotoxicity halted further development but did lead to new generation of gepants, which have been shown to be safe, efficacious and well tolerated.

Zavegepant clinical studies

Zavegepant nasal spray is a third generation gepant and the first, non-oral gepant. In a randomised, dose-ranging, placebo-controlled, phase 2/3 trial in adults aged ≥18 years with migraine, single doses of 10 or 20 mg, of the drug were shown to be effective for the acute treatment of migraine and with a favourable safety profile.

Further data on the efficacy of zavegepant and which formed the basis for the approval, came from a double-blind, randomised, placebo-controlled phase 3 trial in adults with a history of two to eight moderate or severe migraine attacks per month. 

The results showed that among those assigned to zavegepant, two hours after the treatment dose, a statistically significant higher proportion of zavegepant patients had freedom from pain and freedom from their most bothersome symptom.

In addition, twice as many patients (16% vs 8%) given zavegepant reported pain relief after only 15 minutes. There were also significant differences (compared to placebo) for 13 of the 17 pre-specified secondary outcomes.

The trial also found that the drug was well tolerated with the most common adverse reactions reported in at least 2% of patients and at a frequency greater than placebo, were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting.

First drug receives FDA approval for ultra rare neurodegenerative disorder

6th March 2023

Omaveloxolone is the first drug to receive FDA approval for the progressive genetic neurodegenerative disorder, Friedreich’s ataxia

The manufacturer Reata has announced that its drug omaveloxolone (brand name SKYCLARYS) has become the first treatment to be approved for the treatment of Friedreich’s ataxia, an ultra-rare, genetic, progressive neurological disorder.

Friedreich’s ataxia represents an inherited autosomal recessive disease, that affects the nervous system, producing a progressive ataxia, weakness and sensory deficits. The disease has a median onset age of 10 to 15 years and affects approximately 1 in 50,000 people worldwide. Friedreich’s ataxia is due to a lack of function in a gene responsible for the production of frataxin, a protein involved in mitochondrial iron homeostasis.

During conditions of cellular oxidative stress, there is activation of the transcription factor, NF-E2-related factor and which triggers a cellular antioxidant response, through induction of antioxidant response element driven genes. However, it appears that a lack of frataxin impairs NF-E2 signalling and this is though a contributory factor for the neuro-degeneration seen in Friedreich’s ataxia. Omaveloxolone has been shown to induce NF-E2 and thus protect cells from oxidative stress.

Omaveloxolone clinical efficacy

An initial dosing ranging study identified that a dose of 160 mg/day appeared to improve neurological function. Following on from this, a phase 2 randomised, placebo-controlled trial with 103 patients, demonstrated that omaveloxolone 150 mg daily, significantly improved the modified Friedreich’s Ataxia Rating Scale (mFARS) score after 48 weeks compared to placebo (p = 0.014). In an open label extension trial, after 72 weeks, the response to omaveloxolone compared to placebo was maintained.

Following the FDA approval, the company has created the Reata Education, Access, and Care Helpline (REACH), an integrated specialty pharmacy and patient services program, designed to help eligible patients access prescribed Reata medicines. 

While yet to be approved, omaveloxolone has been granted Orphan Drug designation in Europe for the treatment of Friedreich’s ataxia and is currently under review by the European Medicine Agency.

Syfovre approved for geographic atrophy in advanced age-related macular degeneration

24th February 2023

According to a press release from the manufacturer Apellis Pharmaceuticals, syfovre (pegcetacoplan), is to become the first FDA approved therapy for geographic atrophy secondary to age-related macular degeneration which is a leading cause of blindness.

Geographic atrophy (GA) represents an advanced form of age-related macular degeneration and which leads to progressive and irreversible loss of vision. Age-related macular degeneration is a common condition with one US analysis suggesting an annual incidence of 3.5 per 1,000 individuals, around 293,000 new cases per year in those 50 years of age and older.

Globally, the condition is estimated to affect some 5 million people and the median time to the development of central GA following any GA diagnosis is 2.5 years, with an average visual acuity decrease of 22 letters after 5 years.

The complement system is a component of the immune system that is central to the detection and destruction of invading pathogens and consists of three pathways. Moreover, dysregulation of this system is thought to be implicated in the development of age-related macular degeneration.

Syfovre is a complement C3 inhibitor (i.e., one of these pathways) and data from a phase 2 trial showed that the drug produced significant reductions in the growth of GA compared to sham treatment.

Syfovre phase 3 clinical studies

The approval of syfovre was based on the data from two trials, OAKS and DERBY, both of which were randomised, sham trials of 24 months duration and where syfovre (15 mg/0.1ml) was administered either monthly or every other month.

The results showed that in OAKS, monthly syfovre treatment reduced the rate of GA growth by 22% and by 18% when used every other month. Similarly, data from DERBY observed a 18 and 17% reduction in GA growth rate for monthly and alternate monthly injections respectively. Further details on the product can be found in the full prescribing information sheet.

According to the press release, syfovre is currently under review by the European Medicines Agency with a decision expected in early 2024.

FDA approves ruxolitinib cream for vitiligo

28th July 2022

Ruxolitinib cream has become the first FDA-approved treatment for the re-pigmentation of skin in patients with non-segmental vitiligo

Ruxolitinib cream has been approved by the US Food and Drug Administration for the treatment of non-segmental vitiligo, the manufacturer Incyte has announced.

Ruxolitinib is a Janus kinase inhibitor and the cream has already shown anti-inflammatory and prompt antipruritic effects in the management of patients with atopic eczema.

The FDA decision to approve ruxolitinib (brand name Opzelura) was based on the findings of two clinical trials, TRuE-V1 and TRuE-V2. Both were similar in design and evaluated the efficacy and safety of ruxolitinib cream in adolescent (12 years and older) and adult participants with non-segmental vitiligo for whom the vitiligo involved area (facial and non-facial) did not exceed 10% of their body surface area (BSA).

In each of the trials, participants were randomised received ruxolitinib cream 1.5% or vehicle for 24 weeks which was applied twice daily. Following on from the initial 24 week period, participants were offered the opportunity to continue in the treatment extension arm for up to 52 weeks.

The primary endpoint for both trials was the facial Vitiligo Area Scoring Index (F-VASI75) and a 75% improvement from baseline in the F-VASI (F-VASI75) has been identified as within-patient clinically meaningful thresholds.

Ruxolitinib cream: clinical efficacy

A dose ranging Phase II randomised trial did provide evidence for the effectiveness of the treatment. In the trial, 157 patients (mean age, 48·3 years, 46% male), with depigmentation of 0·5% or more of their facial body surface area (BSA) and 3% or more of their non-facial BSA, were randomised 1:1:1:1 to receive ruxolitinib cream (1·5% twice daily, 1·5% once daily, 0·5% once daily, or 0·15% once daily) or vehicle twice daily.

The primary endpoint was a F-VASI50 after 24 weeks and this was achieved after 24 weeks by 45% of patients using the 1.5% cream twice daily and 50% of those using the same strength once daily compared to only 3% receiving placebo.

Although the results of TRuE-V1 and V2 are not yet published, the manufacturer reports that after 24 weeks, approximately 30% of patients using ruxolitinib cream achieved the primary endpoint compared with approximately 8% of those using the vehicle in TRuE-V1 and 13% in TRuE-V2.

Additionally, after 24 weeks, more than 15% of those receiving ruxolitinib cream achieved a F-VASI90 (i.e., 90% improvement from baseline), compared to approximately 2% of patients treated with vehicle.  At week 52, approximately 50% of ruxolitinib cream patients achieved the primary endpoint and 30% had achieved a F-VASI90.

Vitiligo has two main types, non-segmental and segmental with the former being symmetrical, whereas the latter is more localised. Non-segmental vitiligo is the more common form and accounts for 85–90% of cases.

Ruxolitinib cream has yet to be approved by the European Medicines Agency, but it is currently under review by the organisation.

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