FDA Grants Approval to Vemurafenib for Erdheim-Chester Disease


Approval is based on an open-label, multicentre, single-arm, multiple cohort clinical trial in patients aged 16 years of age and older

On 6 November 2017, the US Food and Drug Administration (FDA) granted regular approval to


vemurafenib
(ZELBORAF, Hoffmann-La Roche Inc.) for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation.

Approval was based on an open-label, multicentre, single-arm, multiple cohort clinical trial in patients aged 16 years of age and older. The trial included 22 patients with BRAF V600 mutation- positive ECD. The best overall response rate, as assessed by the investigator using RECIST v1.1, was 54.5% (n=12) (95% CI: 32.2, 75.6). Eleven partial responses (50%) and 1 complete response (4.5%) were observed. The median duration of follow- up was 26.6 months (range: 3.0 to 44.3 months). The median time to response was 11 months (95% CI: 3.7, 14.6). The median response duration was not estimable.

In the trial, the most commonly reported adverse reactions (>50%) in patients with BRAF V600 ECD were arthralgia, maculo-papular rash, alopecia, fatigue, prolonged QT on electrocardiogram, and skin papilloma. The most common (≥ 10%) grade ≥ 3 adverse reactions were squamous cell carcinoma of the skin, hypertension, maculo-papular rash, and arthralgia. The incidence of adverse reactions resulting in permanent discontinuation was 32%.

The recommended dose of vemurafenib is 960 mg orally twice daily taken approximately 12 hours apart with or without a meal.

Full prescribing information is available
here
.  

FDA granted this application priority review. Breakthrough Therapy and Orphan Drug designations for this indication were also granted.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

About Erdheim-Chester Disease

It is a rare disease characterised by abnormal multiplication of histiocytes or tissue macrophages. Onset is typically in middle age. The ECD is associated with high mortality rates.

The first case of ECD was reported by the American pathologist William Chester in 1930, during his visit to the Austrian pathologist Jakob Erdheim.

The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalised sclerosis of the long bones. Long bone involvement is almost universal in ECD patients and is bilateral and symmetrical in nature. More than 50% of cases have extraskeletal involvement.

Bone pain is the most frequent of all symptoms associated with ECD and mainly affects the lower limbs, knees and ankles. The pain is often described as mild but permanent, and juxtaarticular in nature.

Radiologic osteosclerosis and histology are the main diagnostic features. Histologically, ECD differs from Langerhans cell histiocytosis.

Approximately half patients with ECD harbour point mutations of the BRAF gene at codon 600. 

Generic Fulvestrant Receives a Positive Opinion from the EMA CHMP


Fulvestrant Mylan is a generic of Faslodex, which has been authorised in the EU since 2004

On 9 November 2017, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending granting a marketing authorisation for the medicinal product


Fulvestrant
 Mylan, intended for the treatment of locally advanced or metastatic breast cancer.

The applicant for this medicinal product is Mylan S.A.S.

Fulvestrant Mylan will be available as a 250-mg solution for injection. The active substance of Fulvestrant Mylan is fulvestrant, an anti-oestrogen which attaches to the receptors for oestrogen on the surface of cells, thereby blocking the effects of the hormone and causing the number of oestrogen receptors to fall (ATC code: L02BA03). As a result, the tumour cells are not stimulated to grow by oestrogen and the growth of the tumour is reduced.

Fulvestrant Mylan is a generic of Faslodex, which has been authorised in the EU since 10 March 2004.

Studies have demonstrated the satisfactory quality of Fulvestrant Mylan. Since Fulvestrant Mylan is of the same type of solution, contains the same concentration of the active substance and has the same excipients in similar amounts as the medicinal product currently approved, a bioequivalence study versus the reference product Faslodex was not required.

The full indication is:

Fulvestrant is indicated for the treatment of oestrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women:

  • not previously treated with endocrine therapy, or
  • with disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on anti-oestrogen therapy.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission. 

Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion. 

EMA Recommends Approval of Biosimilar Bevacizumab


Bevacizumab is indicated for the treatment of carcinoma of the colon or rectum, breast cancer, NSCLC, RCC, epithelial ovarian, fallopian tube or primary peritoneal cancer, and cervical carcinoma

On 9 November 2017, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Mvasi, intended for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix.

The applicant for this medicinal product is Amgen Europe B.V.

Mvasi will be available as a 25 mg/ml concentrate for solution for infusion. The active substance of Mvasi is


bevacizumab
, a monoclonal antibody (ATC code: L01XC07) which binds to vascular endothelial growth factor (VEGF), the key driver of vasculogenesis and angiogenesis, thereby inhibiting the binding of VEGF to its receptors on the surface of endothelial cells. Neutralising the biological activity of VEGF regresses the vascularisation of tumours, normalises remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth.

Mvasi is a biosimilar medicinal product. It is highly similar to the reference product Avastin (bevacizumab), which was authorised in the EU on 12 January 2015. Data show that Mvasi has comparable quality, safety and efficacy to Avastin.

The full indication is:

Mvasi in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum.

Mvasi in combination with


paclitaxel
is indicated for first-line treatment of adult patients with metastatic breast cancer.

Mvasi, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer (NSCLC) other than predominantly squamous cell histology.

Mvasi, in combination with erlotinib, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous NSCLC with epidermal growth factor receptor (EGFR) activating mutations.

Mvasi in combination with


interferon alfa-2a
is indicated for first-line treatment of adult patients with advanced and/or metastatic renal cell cancer (RCC).

Mvasi, in combination with


carboplatin
and paclitaxel is indicated for the front-line treatment of adult patients with advanced (International Federation of Gynecology and Obstetrics (FIGO) stages IIIB, IIIC and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Mvasi, in combination with carboplatin and


gemcitabine
or in combination with carboplatin and paclitaxel, is indicated for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.

Mvasi in combination with paclitaxel,


topotecan
, or pegylated 


liposomal doxorubicin
is indicated for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.

Mvasi, in combination with paclitaxel and


cisplatin
or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.

It is proposed that Mvasi be prescribed by physicians experienced in the use of antineoplastic medicinal products.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.