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39933711000001101

New Medicines

PemazyreIntrahepatic bile duct cancer (cholangiocarcinoma) with fibroblast growth factor receptor rearrangements

Information

Pemazyre
New molecular entity
Incyte
Incyte

Development and Regulatory status

Launched
Approved (Licensed)
Launched
July 2021
Yes
Yes
Jul 21Pemazyre 4.5mg, 9mg and 13.5mg tablets available in the UK. Price for 14 tablets = £7159.00 [16].
May 21Incyte are funding pemigatinib via a post-EAMS agreement with NHS England and it is now available on blueteq for doctors to register new patients. NHSE Specialised commissioning pharmacy leads have been advised of the change[15].
Apr 21Full indication "Pemazyre monotherapy is indicated for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy" [14].
Apr 21MHRA grants orphan drug status to pemigatanib. As the MHRA grants this status at the time of authorisation, it can be assumed that the MHRA has licensed pemigatanib but at present no further details are available [13].
Mar 21Approved in EU [12]
Jan 21Recommended for conditional EU approval by CHMP - the full indication is "for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy." It should be prescribed by physicians experienced in the diagnosis and treatment of patients with biliary tract cancer [11]. Conditional approval indicates that the information available is less than would usually be required, but that the medicine fulfils a significant unmet need and the benefit to risk balance is considered to be acceptable under those circumstances; the manufacturer will normally be expected to provide further clinical data to retain the marketing authorisation.
Jan 21Granted Early Access to Medicines Scheme (EAMS) status by MHRA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with fibroblast growth factor receptor 2 fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy [10].
May 20Launched in the US [9].
Apr 20The FDA has approved pemigatinib(Pemazyre™), a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma [8].
Jan 20The EMA has validated the Marketing Authorization Application for pemigatinib for the treatment of adults with locally advanced or metastatic cholangiocarcinoma [7].
Dec 19FDA accepts NDA for pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements [6].
Oct 19Has orphan drug status in EU & US [4,5].
Jun 19FDA has granted pemigatinib Breakthrough Therapy designation for the second-line treatment of cholangiocarcinoma [1].

Category

Inhibitor of fibroblast growth factor receptor (isoforms 1 2 and 3).
Cholangiocarcinoma arises from the cells within the bile ducts. It is often diagnosed late (stages III and IV) and the prognosis is poor. It is most common in those over 70 years old and is more common in men than women [1]. Incidence is 1-2 per 100,000 population per year in the UK [2].
Intrahepatic bile duct cancer (cholangiocarcinoma) with fibroblast growth factor receptor rearrangements
Oral

Further information

Yes

Trial or other data

Apr 20FDA approval was based on data from the FIGHT-202 study, a multi-center, open-label, single-arm study that evaluated Pemazyre as a treatment for adults with cholangiocarcinoma. In patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% (primary endpoint), and median DOR of 9.1 months (secondary endpoint) [8].
Jun 19First patient dosed in PIII trial FIGHT302 (NCT03656536), an open-label, randomized, active-controlled study evaluating the safety and efficacy of pemigatinib compared to gemcitabine plus cisplatin chemotherapy (current standard of care) [1]. Estimated primary completion date March 2022 [3].

Evidence based evaluations

PemazyreMyeloproliferative neoplasms (MPNs) with fibroblast growth factor receptor-1 rearrangements

Information

Pemazyre
Licence extension / variation
Incyte
Incyte

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Launched
Aug 22FDA has approved pemigatinib for the treatment of relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements [6]

Category

Inhibitor of fibroblast growth factor receptor (isoforms 1 2 and 3).
MPNs begin with an abnormal mutation in stem cells in the bone marrow, which leads to an overproduction of any combination of white cells, red cells and platelets. MPN with FGFR1 rearrangement comprise a rare, aggressive, and clinically heterogeneous class of hematologic malignancies that share characteristic rearrangement of the FGFR1 gene at the 8p11 locus [1,2]. Th mostly develop in adults aged >60 years; around 4,180 cases are diagnosed in the UK each year [3,4].
Myeloproliferative neoplasms (MPNs) with fibroblast growth factor receptor-1 rearrangements
Bladder instillation

Trial or other data

Aug 22Results of PII FIGHT-203 study (NCT03011372, n=28) are announced. In pts with chronic phase in the marrow with or without extramedullary disease (N = 18), the complete response (CR) rate was 78% (14/18; 95% CI 52, 94). The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days). In pts with blast phase in the marrow with or without extramedullary disease (N = 4), two pts achieved a CR (duration: 1+ and 94 days). In pts with extramedullary disease only (N = 3), one pt achieved a CR (duration: 64+ days). For all patients (N = 28 including three patients without evidence of morphologic disease) the complete cytogenetic response rate was 79% (22/28; 95% CI: 59, 92). The most common adverse reactions were hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhoea and dry eye [6]
Mar 17Recruitment to PII FIGHT-203 study (NCT03011372), in which patients with myeloproliferative neoplasms with fibroblast growth factor receptor-1 rearrangements will receive pemigatinib begins. Approximately 47 patients will be recruited at sites in the US, EU and UK. Primary outcome measure is proportion of participants who achieve a complete response. Estimated primary completion date is June 23 [5].