Dupixent approved for severe atopic dermatitis in children from 6 months

30th January 2023

Dupixent has had a license extension in the EU so that it can now be used to treat severe atopic dermatitis in children from 6 months of age

In a press release from Regeneron, the company described how data from a study in the Lancet, showed that Dupixent treatment plus topical corticosteroids (hydrocortisone 1%) was effective in children under 6 years of age. The Lancet trial enrolled and randomised 162 children aged 6 months to 6 years, to the drug or placebo. In the trial, participants were included if they had an Investigator’s Global Assessment (IGA) score of 3 – 4, which represents moderate to severe disease. The drug was given at a dose based on the bodyweight. For instance, if > 5 kg but < 15 mg, a dose of 200 mg was given once every 4 weeks and for children weighing > 15 kg but < 30 kg, a dose of 300 mg was given. The primary endpoint was set as the proportion of participants with an IGA score of 0 or 1 (i.e., clear or almost clear) skin after 16 weeks. At week 16, there was a 24% difference in IGA scores between Dupixent and placebo and which was statistically significant (p < 0.0001). The study also observed that the drug’s safety profile was generally in line with what might be expected.

The press release describes how in practice, 85 to 90% of children will develop atopic eczema before the age of 5 years and in Europe alone, it is estimated that up to 80,000 children aged between 6 months and 5 years have uncontrolled severe atopic dermatitis and might therefore benefit from a trial of systemic therapy. According to the EMA, Dupixent will now be indicated for the treatment of severe atopic dermatitis in children 6 months to 11 years and who are candidates for systemic therapy.

The drug was approved for the same paediatric population by the FDA in June 2022.

CHMP recommends Enhertu for HER2-low breast cancer treatment

5th January 2023

The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on Enhertu for treating HER2-low breast cancer

According to a press release by the manufacturer AstraZeneca, the  Committee for Medicinal Products for Human Use (CHMP), has adopted a positive opinion recommending a change to the marketing authorisation for Enhertu. The drug can now be used as monotherapy for the treatment of adult patients with unresectable or metastatic HER2‑low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

The World Health Organisation estimates that in 2020, there were 2.3 million women diagnosed with breast cancer and which led to 685 000 deaths. In Europe alone in 2020, there were 531,086 cases of breast cancer that resulted in 141,765 deaths. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase normally involved in the proliferation and division of breast cells and HER2-positive breast cancers are an aggressive type of breast cancer that tend to grow faster and are more likely to spread. It is known that around 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridisation. Moreover, this low HER2 expression is a promising new target for antibody-drug conjugates and Enhertu (which contains trastuzumab deruxtecan) is one such specifically engineered HER2-directed antibody drug conjugate.

Enhertu clinical efficacy

CHMP based its decision of data from the DESTINY-BREAST04 trial which compared previously treated patients with HER2-low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridisation (ISH)-negative) unresectable and/or metastatic breast cancer with hormone receptor (HR) positive or HR-negative disease against standard of care physician’s choice of chemotherapy. The study found that Enhertu demonstrated a 49% reduction in the risk of disease progression or death versus physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer with HR-positive disease (PFS hazard ratio, HR = 0.51, 95% CI 0.40 – 0.64, p < 0.001). In addition, the median overall survival in the hormone receptor–positive cohort was 23.9 months in the Enhertu group and 17.5 months in the physician’s choice group (HR for death = 0.64, 95% CI, 0.48 to 0.86, p = 0.003).

The press release adds how the safety profile of Enhertu was consistent with previous clinical trials with the most common Grade 3 or higher treatment-emergent adverse events were neutropenia (13.7%), anaemia (8.1%), fatigue (7.5%), leukopenia (6.5%), thrombocytopenia (5.1%) and nausea (4.6%).

A summary of the CHMP provides details on the full indications for Enhertu.

CHMP recommends conditional marketing authorisation for multiple myeloma monotherapy

22nd July 2022

The Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorisation for Tecvayli® (teclistamab).

Teclistamab is an off-the-shelf, T-cell redirecting bispecific antibody. It targets both B-cell maturation antigen, a marker found on multiple myeloma cells, and CD3, on T-cells. It is recommended as monotherapy for adult patients with relapsed and refractory multiple myeloma (RRMM), who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

In December 2021, the EMA granted accelerated assessment for teclistamab. Accelerated assessment reduces the timeframe for the CHMP to review a marketing authorisation application and is granted when a medicinal product is of major interest for public health and therapeutic innovation.

The CHMP recommendation is based on positive results from the multicohort, open-label, Phase I/II MajesTEC-1 study (NCT03145181 and NCT04557098), evaluating the safety and efficacy of teclistamab in adults with RRMM.

The latest findings from the study were presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting and published in The New England Journal of Medicine. Teclistamab resulted in deep and durable responses in patients with triple-class exposed multiple myeloma (n=165). With a median follow-up of approximately 14 months (14.1), the overall response rate was 63% (95% CI: 55.2–70.4), with 39.4% having a complete response (CR) or better. Almost half (46%) of patients who achieved a CR or better were minimal residual disease-negative.

Adverse events (AEs) were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1/2. The most common AEs were cytokine release syndrome and neutropenia. Infections were frequent (76.4%; 44.8% Grade 3 or 4). The overall incidence of neurotoxic events was low and five patients had immune effector cell-associated neurotoxicity syndrome. There were five treatment-related deaths, and dose reductions and discontinuations due to AEs were infrequent.