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Press Releases

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

Berotralstat approved for recurrent attacks of hereditary angioedema

17th September 2021

Hereditary angioedema (HAE) is a rare, inherited disorder that presents with unpredictable, recurrent attacks of oedema, leading to a rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. The condition affects around 1 in 50,000 of the population in the UK, which equates to around 1,500 people and the condition often first presents between the ages of 5 and 11 years.

The underlying cause of HAE is a mutation of the SERPING1 gene which codes for a protein, C1 esterase inhibitor (CI IHB), which regulates inflammatory pathways. This mutation can result in either low levels of C1 IHB, which is the most common presentation (type 1), accounting for around 85% of cases, or normal levels of C1 IHB, but with a reduced function (type 2). There is also a third, much rarer type characterised by normal C1 IHB levels but other mutations which also give rise to elevated levels of bradykinin. Irrespective of the underlying cause, reduced functioning of C1 IHB leads to an increased production of the vasoactive peptide, bradykinin which mediates vasodilation in subcutaneous or submucosal tissues.

The aim of treatment is to either reverse or prevent attacks with a view to improving patient’s quality of life. Treatments have been based on prophylactic use of C1 IHB concentrates, some of which have been developed as injectables for self-administration. In contrast, berotralstat, is an oral, once daily inhibitor of plasma kallikrein which is hydrolysed to release bradykinin.

NICE Approval

The NICE approval was based on the findings of the randomised phase 3 trial, APex-2, a double-blind, parallel-group study in which patients were randomised 1:1:1, to receive once-daily berotralstat in a dose of 110 mg, 150 mg or placebo. In APex-2, the primary efficacy end point was defined as the rate of investigator-confirmed HAE attacks during the 24-week treatment period. The study found that use of berotralstat led to a significant reduction in attack rate at both 110 mg (1.65 attacks per month, p = .024) and 150 mg (1.31 attacks per month, p < .001) relative to placebo (2.35 attacks per month). An extension of APex-2 was published in June 2021 in which patients originally assigned to placebo were randomised to either 110 mg or 150 mg of berotralstat and followed for 48 weeks. At the study end, mean attack rates for the 150mg group declined from a baseline of 3.06 attacks/month to 1.06 at week 48. Similarly, for the 110mg group, attack rates reduced from a baseline of 2.97 to 1.35 at week 48.

NICE has declared berotralstat is an innovative prophylactic treatment for recurrent attacks of hereditary angioedema and recommended that the drug can be used under the following circumstances.

In people 12 years and older, only if:
• they have at least 2 attacks per month and
• it is stopped if the number of attacks per month does not reduce by at
least 50% after 3 months.

Source: NICE. Berotralstat for preventing recurrent attacks of
hereditary angioedema
, September 2021.

NICE approves pemigatinib for patients with advanced cholangiocarcinoma

23rd July 2021

The oral kinase inhibitor, pemigatinib, has been approved by NICE as a second-line therapy for patients with advanced cholangiocarcinoma.

Cholangiocarcinoma (CCA) or bile duct cancer, is a rare cancer with an approximate incidence of 3.58 cases per 100,000, occurs in the tubes carrying bile into the digestive system. It can be further subdivided into two forms, depending on whether it develops within the liver (intrahepatic, iCCA) or extrahepatic (eCCA). According to Cancer Research UK, there are an estimated 1900 cases of iCCA each year but far fewer (530) cases of eCCA. Unfortunately, CCA is often asymptomatic in the early stages of the disease and consequently, it has been estimated that around 70% of patients are diagnosed at late stages due to this lack of symptoms. Figures for 2012 indicate that the 5-year survival is in both sexes is only around 5%, and in 2017, there were a total of 2523 deaths in England alone. Since a large proportion of patients are diagnosed at a late stage of the disease, surgical resection (which is perceived as the only curative treatment), is no longer an option.

Studies have shown that two-thirds of patients with cholangiocarcinoma have genomic alterations. One such alteration is in the fibroblast growth factor receptor (FGFR) pathway which is responsible for cellular migration, proliferation, survival and differentiation. There are at least four different isoforms of FGFR and genetic aberrations such as chromosomal translocations or fusions in the FGFR pathway, contribute to malignant transformation and have been observed to occur in 13% of iCCA.

Treatment
There are currently no standard care treatments for cholangiocarcinoma and no recognised therapy for patients with FGFR fusion/mutations. Pemigatinib is a potent oral inhibitor of FGFR isoforms and has been shown to be of benefit in patients with cholangiocarcinoma with FGFR alterations. Results from the FIGHT-202 study, in which previously treated patients with advanced metastatic cholangiocarcinoma with FGFR mutations, were given pemigatinib monotherapy at a starting oral dose of 13.5mg daily for a 21-day cycle (two weeks on, 1 week off). Treatment with pemigatinib for a median duration of 8 months in 108 patients, led to an overall treatment response rate of 35.5% which included three complete remission and 35 partial responders. Overall, 71 patients died, mostly because of disease progression although there were no deaths deemed to be treatment-related, leading the authors to conclude that their data supported the therapeutic potential of pemigatinib in previously treated patients with FGFR fusions.

The drug is already approved in Japan, Europe and the US and according to Helen Morement, founder of The Cholangiocarcinoma Charity, ‘the availability of pemigatinib marks a major milestone in the fight against cholangiocarcinoma, bring new hope for our patients with the devastating type of liver cancer”. The decision by NICE will not only give patients an alternative to chemotherapy but also access to molecular testing.

Source. NICE 2021