Sirolimus

Articles · Refrigerated Storage · Medicine Compliance Aid Stability · Lactation Safety Information · New Medicines ·
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Articles

Refrigerated Storage

Rapamune · Pfizer Limited

Pfizer Limited
Rapamune
Oral solution, 1mg/mL

In the event of an inadvertent temperature excursion the following data from manufacturer’s product literature may be used: If necessary, the patient may store the bottles at room temperatures up to 25°C for a short period of time (24 hours).

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

Pfizer have stated that they should be contacted in all cases where a deviation from the recommended storage conditions has occurred. See contact details in current BNF.

 

26th September 2018
London MI Service

Medicine Compliance Aid Stability

Rapamune · Pfizer Ltd

Pfizer Ltd
Rapamune
Tablets coated 500 micrograms, 1mg, 2mg
A3 · Amber 3 · No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Protect from light
Protect from light in an airtight container.
18th September 2015

Lactation Safety Information

See summary
Long half-life increases risk of accumulation in breastfed infants
Low levels anticipated in milk due to the drug's properties
May interfere with lactation
No published evidence of safety
Monitor infant plasma levels if there is a concern about toxicity
16th September 2020

New Medicines

Rapamune · Lymphangioleiomyomatosis (LAM)

Information

Rapamune
Licence extension / variation
Pfizer
Pfizer

Development and Regulatory status

Launched
Launched
Launched
August 2018
Aug 18 · Licence change approved in EU [6].
Jun 18 · EU positive opinion for a licence change for treatment of patients with sporadic lymphangioleiomyomatosis with moderate lung disease or declining lung function [5].
May 16 · Not listed in Pfizer pipeline [4].
Jun 15 · Approval by the FDA for a treatment for lymphangioleiomyomatosis [3].
Feb 15 · Pfizer expects a decision from the FDA in Jun 15 [1].
Feb 15 · US FDA accepts for priority review a supplemental New Drug Application of Rapamune for lymphangioleiomyomatosis [1].

Category

Inhibits proliferation of activated T-cells by inhibiting cytokine-mediated signal transduction pathways
LAM is a rare progressive lung disease that usually affects women during their childbearing years and results from abnormal growth of smooth muscle-like cells. Over time, the abnormal growth of these cells can cause airway obstruction [1].
Lymphangioleiomyomatosis (LAM)
Oral

Trial or other data

Feb 15 · Pfizer noted that it provided study drug and a portion of the funding but had no involvement in the design or conduct of the LAM trial [1].
Feb 15 · The US filing is based on results from a trial involving 89 LAM patients with moderate lung impairment who were randomised to receive Rapamune or placebo. Those treated with the drug for one year experienced stabilisation of lung function. If approved, Rapamune would be the first FDA-approved treatment option for LAM [1].

Evidence based evaluations

SMC

Opsiria · Chronic non-infectious, posterior segment uveitis

Information

Opsiria
New formulation
Santen
Santen

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Oct 19 · Still listed in Santen pipeline [13].
Nov 18 · Still listed in Santen pipeline. Planning to start an additional clinical trial in Nov 18 in the U.S. NDA filed in April 2015 in Asia [11].
Dec 17 · In the US, a complete response letter was issued indicating the FDA was unable to approve the application and requesting additional substantiating evidence to demonstrate efficacy [10].
Apr 17 · NDA submitted to FDA [9].
Nov 16 · Santen is looking at the totality of data from the Sakura programme, and plans to file its NDA to the FDA next year [8].
May 16 · EU filing withdrawn as the company acknowledged the need to submit additional data on the benefits of Opsiria from an ongoing clinical study [6].
May 16 · Santen plans to resubmit in Europe [7].
Mar 15 · Filed in the EU. The EMA has accepted the filing for treatment of noninfectious uveitis (NIU) of the posterior segment, which is supported by data from SAKURA [5].
Oct 12 · PIII study, SAKURA, (Sirolimus double-masKed Uveitis tReAtment) started May 11 [1].
Oct 12 · Granted orphan drug status in the US in Nov 11 [3].
Oct 12 · Granted orphan designation (EU/3/11/898) in the EU Aug 2011 [2].

Category

Inhibits proliferation of activated T-cells by inhibiting cytokine-mediated signal transduction pathways
chronic non-infectious uveitis affects ~ 4.1 in 10,000 people in the EU; equivalent to a total of around 208,000 people [2].
Chronic non-infectious, posterior segment uveitis
Intravitreal

Trial or other data

Nov 18 · PIII study (NCT03711929) to assess the efficacy and safety of DE-109 440 µg every 2 months in subjects with active, non-infectious uveitis of the posterior segment of the eye (NIU-PS) starts. There is a 6-month, single-arm, open-label period after completion of the 6-month double- masked, controlled period allows the evaluation of the efficacy and safety of intravitreal injection of DE-109 440 µg every 2 months for longer duration than appropriate for a placebo or sham control. 200 adults will be recruited in the US. Collection of primary outcome data (vitreous haze [VH] of zero response at month 3) is due to complete Feb 21 [12].
Nov 16 · Santen announces data from PIII SAKURA Study 2. The difference in the effect (of vitreous haze) between the low dose of the drug (44µg) and the 440µg dose was not statistically significant [8].
Apr 14 · The PIII SAKURA 1 (Study Assessing double‐masKed Uveitis tReAtment) study met its primary endpoint - the proportion of patients achieving a vitreous haze score of zero at month 5 (Standardized Uveitis Nomenclature [SUN] Photographic scale). 347 patients with non-infectious posterior, intermediate or panuveitis were randomized into three treatment arms, each receiving different doses of sirolimus by intravitreal injection. SAKURA Study 2 continues to enroll patients under the same protocol [4].
Oct 12 · NCT01358266 A PIII multinational, multicentre, randomized, double-masked study of 3 doses of sirolimus for the treatment of 500 patients with active, non-infectious uveitis. The primary outcome is the proportion of subjects with vitreous haze score at 5 months. The study started in May 11 and is due to complete Oct 14 [1].

Evidence based evaluations

Chronic kidney disease - prevention of failed arteriovenous (AV) fistula maturation - implantable collagen matrix

Information

New formulation
Vascular Therapies
Vascular Therapies

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes

Category

Sirolimus is a cell cycle inhibitor, which may prevent hyperplasia and vein stenosis after AV fistula surgery. Single perivascular implant delivered to the vessel wall at and around the site of anastomosis of an AV fistula immediately following surgery.
There were 3,663 first access haemodialysis patients in 2013, 40.7% of which started therapy on an AV fistula [1].
Chronic kidney disease - prevention of failed arteriovenous (AV) fistula maturation - implantable collagen matrix
Implantation

Pachyonychia congenita - topical formulation

Information

New formulation
Palvella Therapeutics
Palvella Therapeutics

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Cream formulation to deliver sirolimus (1%) topically. Sirolimus acts as a ‘mammalian target of rapamycin’ (mTOR) inhibitor to reduce the amount of abnormal keratin preventing formation of blisters and callouses [2].
Pachyonychia congenita (PC) is an ultra-rare inherited, severe and chronically debilitating skin disorder caused by mutations in certain keratin genes. The disorder is manifested by the overproduction of keratin leading to painful conditions including blisters and callouses on the feet that impact mobility, as well as thickened nails, cysts and sores. PC affects <0.01 in 10,000 people in the EU, equivalent to a total of <500 people [2,3]
Pachyonychia congenita - topical formulation
Topical