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Safety in Lactation: Somatostatin analogues

21 September 2020Somatostatin analogues are indicated for a variety of conditions including acromegaly, neuroendocrine tumours, especially carcinoid, and Cushing’s disease. As the indications vary between the three…
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Refrigerated Storage

SandostatinNovartis Pharmaceuticals

Novartis Pharmaceuticals
Sandostatin
Solution for injection / infusion 50 microgram/1mL, 100 microgram/1mL, 500 microgram/1mL

In the event of an inadvertent temperature excursion the following data may be used:
The ampoules may be stored below 30°C for up to two weeks.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

26 January 2022
London MI Service

Sandostatin LARNovartis Pharmaceuticals

Novartis Pharmaceuticals
Sandostatin LAR
Powder and solvent for suspension for injection (10mg, 20mg and 30mg)

In the event of an inadvertent temperature excursion the following data may be used:
Sandostatin LAR may be stored below 25°C on the day of the injection

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

26 January 2022
London MI Service

OctreotideSun Pharmaceuticals UK Limited

Sun Pharmaceuticals UK Limited
Octreotide
50, 100 and 500 micrograms/ml solution for injection (ampoules), 200 micrograms/ml solution for injection (multi-dose vials)

In the event of an inadvertent temperature excursion the following data may be used:
Unopened ampoules/vials may be stored at 25°C for up to 4 weeks.
Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

No if exposed to conditions described above
Yes if exposed to conditions described above
16 October 2020
London MI Services

OctreotideHospira UK Ltd (part of Pfizer)

Hospira UK Ltd (part of Pfizer)
Octreotide
Solution for Injection

In the event of an inadvertent temperature excursion the following data may be used:

In-house data from the manufacturer indicate that exposure of vials of octreotide acetate stored at room temperature (8°C – 25°C) for a maximum of 72 consecutive hours are stable until expiration date, if returned to storage between 2°C – 8°C.

Vials exposed to temperature excursions of >72 hours at room temperature (8°C – 25°C) are stable for either:

a) 6 months from original manufacturing date

b) 2 weeks at 25°C from initial temperature excursion.

No - if exposed to the excursion conditions above
Yes
29 December 2021
London MI Sevice

Lactation Safety Information

Low levels anticipated in milk due to the drug's properties
Monitor infant for GI disturbances
Used in full-term neonates from birth
Very limited published evidence of safety
11 September 2020

New Medicines

MycapssaAcromegaly - oral formulation

Information

Mycapssa
New formulation
Chiasma
Chiasma

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Yes
Yes
Jan 22Amryt announce positive long-term safety and efficacy data from global OLE of MPOWERED PIII trial (n=60). Patients maintained long-term biochemical response with 94%, 90% & 93% maintaining response at year 1, 2 & 3, respectively. Long-term safety profile was consistent with that observed in prior studies & IGF-1 levels were stably maintained within normal limits [31].
Jun 21Filed in EU as a maintenance therapy for adults with acromegaly [30].
May 21Announced entry into a definitive merger agreement for the acquisition of the company by Amryt Pharma [29].
Jan 21Chiasma expect to submit MAA to EMA mid-21[28].
Nov 20Launched in US [29].
Jun 20Approved in US [27].
Jan 20Chiasma announce US FDA have accepted NDA for octreotide capsules for maintenance therapy of adult patients with acromegaly, with a target action date of 26/6/20 [24].
Jun 19Chiasma expect to submit a NDA to FDA end-2019 with an expected six-month PDUFA review time period [22].
Apr 16FDA Complete Response Letter indicates that the FDA did not consider the application provided substantial evidence of efficacy and recommends that the company carries out a randomised double-blind controlled trial in the US, of sufficient duration to ensure that a stable response can be demonstrated. The company intends to discuss this with the FDA and notes that they are proceeding with a multi-national PIII trial intended to support an application to the EMA (NCT02685709, MPOWERED) that will include patients from the US [16].
Aug 15US FDA has accepted filing of New Drug Application for octreotide capsules, for maintenance of adults with acreomegaly [15].
Jun 15Chiasma submits an application for filing to the US FDA for octreotide capsules in pts with Acromegaly. The application is supported by a multicentre PIII study which was published in the JCEM [14].
Aug 14Roche has withdrawn from its agreement with Chiasma. Chiasma will lead development and commercialisation going forward [11].
Jul 14Octreolin no longer listed in Roche pipeline [10].
Dec 13Filings now planned for 2015 [9].
May 13EU and US filings planned 2014 [6].
Apr 12US filing planned for Q1 2013 [4].
Dec 11Granted orphan drug status in EU in Jun 09 [3]
Aug 11PIII study to start Sep 11 [2].
Aug 11Granted orphan drug status in US Jun 10 [1].

Category

Somatotropin receptor antagonist
Incidence is 3 to 4 per million patients per year. It most often occurs in adults aged 40 to 45 years [7]. The Society of Endocrinology project provides a registry of patients with acromegaly. There are currently 2,700, of an estimated 3,000, patients from 27 UK centres registered [8]
Acromegaly - oral formulation
Oral

Trial or other data

May 20Estimated primary completion date of PIII MPOWERED trial is now August 20, this trial is designed to support a NDA to EU. Chiasma expect to report topline results Q4 20 [25,26].
Nov 19Topline data from PIII MPOWERED study (designed to support EU approval) is expected H2 20 [23].
Jul 19Chiasma announce positive topline results from PIII CHIASMA OPTIMAL trial - 58% of patients on octreotide maintained biochemical control (IGF-1 ≤ 1.0 x ULN) at the end of study vs. 19% on placebo (p=0.008) [22].
Oct 18Enrolment into PIII CHIASMA OPTIMAL (NCT03252353) has completed; topline results are expected Sept 19. Topline results form PIII MPOWERED study (NCT02685709) are expected Q1 2020 [21].
Jan 18Chiasma is conducting a PIII trial CHIASMA OPTIMAL (NCT03252353) under a Special Protocol Assessment agreement reached with the FDA to support potential resubmission of a NDA. Enrollment started in Q3 17. The nine-month trial is expected to enroll 50 adult acromegaly patients and is designed to evaluate proportion of patients who maintain their biochemical response to octreotide capsules compared to placebo [19].
Jan 18Anticipated primary completion date of MPOWERED is Mar 19 and of OPTIMAL is Dec 19 [20].
Mar 16 Chiasma announces initiation of their MPOWERED study (NCT02685709), intended to support filing with the European Medicines Agency. The non-inferiority trial will be open-label, randomized, active-controlled, and will compare the efficacy, safety and patient reported outcomes of Mycapssa to monthly somatostatin analogue injections; estimated enrolment is 150, primary outcome will be insulin-like growth factor-1 (IGF-1) levels over 62 weeks and estimated primary completion date Oct 2018 [17, 18].
Feb 15Results of a PIII multicenter, open-label, dose-titration, baseline-controlled trial published in JCEM. In 155 patients with acromegaly, oral octreotide was effective in controlling IGF-1 and GH after switching from injectable formulations (IFs) for up to 13 months, with a safety profile consistent with approved IFs. [12]
Feb 13Roche and Chiasma have entered into an agreement to develop and commercialise Octreolin, initially for acromegaly and subsequently for neuroendocrine tumors. Roche received a worldwide exclusive license to Octreolin, and will assume responsibility for the commercialization of Octreolin. Genentech will market the product in the US [5].
Aug 11NCT01412424 A PIII study of oral octreolin in patients with 150 acromegaly who are currently receiving parenteral somatostatin analogues. The primary outcome is IGF-1 concentration after 7 months of treatment. Age-normalized IGF-1 concentration is the treatment goal. The study will start Sep 11 and is due to complete Dec 12. The starting dose of oral octreotide is 40 mg/d and will increase to 60 mg/d to 80 mg/d guided by IGF-1 levels [2]. 12/08/2011 10:43:44
Aug 11An oral formulation of octreotide Octreolin utilizes a proprietary Transient Permeability Enhancer (TPE) technology, which enables previously injectable-only drugs to be taken orally.

Acromegaly in adults - monthly subcutaneous formulation

Information

New formulation
Camurus
Camurus

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes

Category

A synthetic octapeptide derivative of naturally occurring somatostatin with similar pharmacological effects, but with a considerably prolonged duration of action. It inhibits pathologically increased secretion of growth hormone, peptides and serotonin.
Incidence in Europe is around 2-4 per million population. However, in the USA, it has recently been estimated to be around 11 per million population per year. Prevalence estimates range from 36-60 per million. It is most often diagnosed in middle-aged adults (average age 40 years). Men and women are equally affected [1].
Acromegaly in adults - monthly subcutaneous formulation
Subcutaneous injection