Q-Sphera™ – Next Generation Somatostatin Analogue delivery system?

 

In my article listing the somatostatin analogues and their drug delivery systems pipeline (click here), there has been a very interesting development in a product called Q-Sphera (was previously known as Q-Octreotide).  In a press release, it was announced that an unnamed ‘pharma giant’ has signed a deal with Midatech Pharma Plc that will see it evaluate the latter’s Q-Sphera drug delivery platform.  Later in Feb 2019, the pharma was identified as China Medical System Holdings Limited (based out of Hong Kong).  Adding to the excitement behind this development, it was announced in Mar 2019 that the Spanish Government had conditionally approved a €6.6m loan that will be used to help commercialise this flagship drug.

Midatech’s Q-Sphera™ is an advanced microencapsulation and polymer-depot sustained release (SR) drug delivery platform produced using a novel and disruptive printing based process, with numerous and distinct advantages over conventional reactor based technologies. From a manufacturing perspective Q-Sphera™ is a precise, scalable, efficient, and environmentally friendly microparticle platform. From a clinical perspective Q-Sphera™ ensures monodispersed microparticles that release active drug compounds into the body in a superior linear tightly controlled and predictable manner over an extended period of time from 1 – 6 months.  An injection lasting 6 months sounds very exciting but I have no more detail on the feasibility or likelihood of such a change in frequency with Octreotide or Lanreotide but the press release does mention the possibility, i.e. “Q-Sphera allows drug compounds to be released into the body in a “highly controlled manner” over a prolonged period of time; potentially from a few days to up to six months.”

What’s the main differences?

The current trials are based on the use of Sandostatin LAR (Octreotide) using the Q-Sphera delivery system (previously known as Q-Octreotide). The key aspects of usability are reconstitution and needle size but there is also an inference that less frequent injections could be possible.   A comparison of the trial output is as follows:

  • Reconstitution: For Sandostatin LAR (SLAR)™ the procedure to prepare the product for injection is a complex 30 step error prone process, taking up to 40 minutes and, once reconstituted, the product has to be given immediately to prevent solidifying and wastage of the injection. For MTD201™ Q-Octreotide the preparation process is a simple 5 – 7 minute procedure, after which the product is stable up to 2 hours. For the nurse preparing and giving the injection, the short and flexible process of MTD201™ has clear advantages over the all consuming SLAR process™.
  • Needle size: For SLAR, a large 19G needle is prescribed for the injection to prevent blockage, and often an even large 18G needle is required for successful injection. For MTD201 Q-Octreotide the precision microencapsulation technology means that a much smaller 21G needle can be used, and there are no blockages. Other Q-Sphera products use even finer needles as small as 27G. The importance of this is evident from the first-in-human phase I data where MTD201 had lower injection pain – 8% for MTD201 versus 25% for SLAR™, and much lower injection site
    tenderness – 8% for MTD201 versus 83% for SLAR.

This is an exciting development and I will keep this article live with further information as I receive it.

Thanks for reading

Ronny

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Ronny Allan’s ‘PoNETry’ © – An Ode to Lanreotide


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Thanks for reading

Ronny

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Disclaimer

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life!



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Lanreotide – it’s calling the shots!

new lanreotide

2019 UPDATE:

Please note a new syringe for Lanreotide will be available in 2019, at least in Ireland and UK which have confirmed dates (UK is end of June rollout begins).  However, Ipsen are committed to roll it out to the rest of Europe, US, Canada, Australia and New Zealand by end of 2019 (details to follow)  following necessary regulatory approvals.

Further information will be communicated to healthcare professionals in advance of this, to enable them to inform their patients, whom have been prescribed Lanreotide. In addition, the patient information leaflet included in the packet will have clear instructions for use. There will be a prominent yellow box located on the outer carton of the medicine, alerting healthcare professionals and patients that a new syringe is contained inside.

The new pre-filled syringe for Somatuline® Autogel® was the result of several studies, involving patients, their caregivers, nurses and other healthcare professionals, to inform and test enhancements to the existing pre-filled syringe. Notable new features are modified ergonomics and handling, a needle shield removal system, an injection process with plunger support and heightened ease of use. The automatic, built-in safety system, which helps to prevent needle stick injury by locking in place following the administration, has not been changed.

Please note that the medicine is still the same and the formulation and storage conditions have not changed.

To see videos about the new injection system:

If you’re in UK, go to this site:

www.ipsensupport.co.uk

Password is Support2019

watch the video

If not in UK, the link might not work.

The picture below is the new injection inside its protective case.

 

 

new lanreotide in case
The new injection in its case

My Lanreotide Experience

When I was discharged from hospital following major surgery in Nov 2010, I knew I would shortly be commencing long-term monthly ‘somatostatin analogue’ treatment and had assumed Octreotide (Sandostatin LAR) would be the drug of choice. However, my Oncologist prescribed Lanreotide (known in the UK as Somatuline Autogel and elsewhere as Somatuline Depot).  Technically this is a hormone therapy (it’s not chemo).

Somatostatin Analogues (Octreotide/Lanreotide) are mainstay treatments for many Neuroendocrine Cancer patients and their introduction is a very significant factor in the improvement of both prognostic outcomes and quality of life.  Both drugs are designed to control Carcinoid Syndrome (but can be used selectively in other NET syndromes) and both have anti-tumour effects.  Check out my Lanreotide vs Octreotide comparison blog.

butt dart with words

Although I didn’t relish the thought of any injection in the ‘rear end’ every 28 days for the rest of my life, I admit to being slightly relieved with his choice.  I had been reading about patient experiences with the alternative, mainly the needle length and the occasional problems mixing the drug prior to injection.  Although Lanreotide has a similar gauge (thickness), the needle is a good bit shorter and is deep subcutaneous rather than Octreotide LAR’s intramuscular (IM) route. No mixing is required as Lanreotide comes prefilled.

If you’re interested in the science, please be aware that a somatostatin analogue is a synthetic (manufactured) version of a naturally occurring hormone which inhibits the peptides and amines that can be dangerously hypersecreted by certain neuroendocrine tumours.

Following an Octreotide Scan, various areas lit up confirming the output from previous CT scans.  It also confirmed new ‘hotspots’ for further investigation.  This specialist scan confirmed I probably had working receptors to receive something known as a Somatostatin Analogue to help with combatting the effects of Carcinoid Syndrome (please note that not having working receptors does not mean there is no benefit of receiving somatostatin analogues). I was therefore prescribed daily Octreotide (self-injecting) whilst I was waiting for my first major ‘debulking’ surgery, This treatment did eventually lessen the main effect of the carcinoid syndrome, facial flushing.  It wasn’t until after my first surgery that the facial flushing was dramatically reduced.  I commenced Lanreotide on 9 Dec 2010 and I haven’t had a facial flush since. It’s worth adding that my Chromogranin A (CgA) blood test (correlated to tumour mass) did not return to normal until after a liver resection 3 months later.  My 5HIAA urine test results (mainly correlated to serotonin levels) returned to normal prior to liver surgery in Apr 2011 indicating the Lanreotide was doing its job! Somatostatin Analogue side effects are to be expected and most people seem to have different and/or greater or lesser effects than others. The daily Octreotide did not bother me too much other than some discolouring of the stomach at the injection sites (i.e. black and blue!) ….I’m more observant nowadays, so it’s possible I may not have recorded this experience properly.

If you read the UK patient leaflet which comes with each injection, you can see a list of potential side effects as long as your arm.  Neuroendocrine Cancer comes with many signs, syndromes, symptoms and suspicions, so I always advise caution and some analysis when assigning reasons for problems encountered.  For North America, the equivalent instructions can be found here (Somatuline Depot). I don’t know precisely why (……. I do have my suspicions), but I’m always very sceptical about the criteria used to compile the list of side effects for any medicine. In my own mind, I’m fairly certain that people have existing symptoms or new symptoms as a result of coincidental treatment that are erroneously labelled under drugs during trials.

You can also self-inject Lanreotide but I’m not ready for that yet!  If you do self inject, please note it the site is “the upper outer part of your thigh”.  Check out the Ipsen leaflet here.

I think the injection site is very important and getting this wrong will worsen the side effects. For the Healthcare Professional or trained family member administration, the site should be the superior external quadrant but not of the whole ‘butt’, it means of the left or right buttock that is being used on an alternative basis.  If nurses think the whole ‘butt’, they might be tempted to stick it quite close to the ‘intergluteal cleft’ – not advisable!

Although the patient leaflets are very clear on how to administer the drug, once the location is established, I always discuss the following with the Nurse before I receive the ‘dart’:

1.  The injection should have been removed from the fridge at least 30 minutes before treatment. However, please note Ipsen clarified in 2019 that the product can be put back in the fridge in the original packaging for later use, provided it has been stored for no longer than 24 hours at below 40 deg C (104 deg F) and the number of ‘temperature excursions’ does not exceed three. If you are taking the drug somewhere to be administered or were waiting on a home visit, this might help with scheduling issues.

2.  Don’t pinch the skin, stretch it.

3.  Put the needle in fast at 90 degrees, inject the drug slow – 20 seconds is recommended. As the drug is viscous, in any case, there is normally some resistance to a fast release.

4. Do not rub or massage the area after as this action can interfere with the formulation of the drug.  This is clearly stated on the drug information leaflet, i.e. ” Apply gentle pressure to the injection site with a dry cotton ball or sterile gauze to prevent any bleeding. Do not rub or massage the injection site after administration”.

My experience with side effects.  People have different experiences with side effects and just because a particular side effect is mentioned, does not mean to say that everyone will be troubled – many patients experience little or none.  For me, over 7 years, I think I can attribute the following to Lanreotide:

  • itching but only on the legs below the knees centred on the ankles – and nearly always the right leg.  Occasionally, the injection site will itch but only for a day or two.  I have a tub of emollient cream (almond oil) on standby which seems to calm it down.  Note …… a little bit of me thinks there could be a connection with vitamin/mineral deficiency and perhaps a coincidental occurrence and this problem seems much less of an issue over 7 years later. EDIT- could have been Hypothyroidism – click here.
  • minor pain at the injection site but this only lasts for an hour or two and I believe this to be associated with the administration of the injection, i.e. if the injection is done properly, I don’t really have this problem except for a second or two as it enters.  Once, I had pain for 10 days.  In my own experience, the best and least painful injections are those done by trained personnel who are confident.
  • small lumps form at the injection site which is alternating superior external quadrant of the each buttock. You may occasionally hear these being called ‘granulomas‘ or ‘injection site granulomas’. The issue of ‘injection site granulomas’ seems to figure in both Lanreotide and Octreotide. Gluteal injection site granulomas are a very common finding on CT and plain radiographs. They occur as a result of subcutaneous (i.e. intra-lipomatous) rather than intramuscular injection of drugs, which cause localised fat necrosis, scar formation and dystrophic calcification. But no-one seems to know why they occur with somatostatin analogues. I find that they are more conspicuous if the injection is done slightly too high which was my initial experience and they took months to fade.  I opted to stand up for the first two injections and I attribute this decision for a slightly too high injection site.  I now lie down which is actually recommended for the smaller and thinner patient. Although the lumps have reduced in size, I have not seen a new lump for some time indicating location might have been the cause. They sometimes show up on scans.  This is not a new problem and has been highlighted for the last 10 years in academic papers.  This particular paper is useful and the conclusion confirms this is not something that should worry patients too much. Read more here
  • fatigue normally within 24-48 hours of the injection but this is not consistent. Not even sure it can be classed as proper fatigue but it’s a ‘you need to sit down and fall asleep‘ feeling! When this occurs, it normally only lasts for 1 day before the normal energy levels return.  Again, like the itching, this appears to be less of an issue today.
  • malabsorption. although the side effects of gastro-intestinal (GI) surgery and gallbladder removal can cause malabsorption issues leading to steatorrhea (basically the inability to digest fat properly); somatostatin analogues can cause or exacerbate existing steatorrhea, as they inhibit the production of digestive/pancreatic enzymes which aid fat digestion.  Most months, I notice a marked but short-term increase in this problem normally within 48-72 hours of the injection.
  • elevated blood glucose.  This is a new issue in 2018 but has been brewing for a year or two. The patient information leaflet for Lanreotide (and for Octreotide) clearly states that this is a potential side effect and also asks those who are already diabetic, to consult their doctor about monitoring doses of diabetic medicine.  I’m working with my doctors to keep my blood glucose down to avoid becoming diabetic.  Please read this article covering the connections between NETs and Diabetes

Watch a useful injection demonstration video here (for administration by a healthcare professional or family member) (click here)

A few years ago, there was some ‘talk’ that somatostatin analogues were also able to stunt or reverse the growth of certain neuroendocrine tumours.  Has this been the case for me?  Possibly.  I’ve had regular CT scans every 3-6 months and since two bouts of major surgery in 2010/2011, I’ve also had 3 x Octreoscans over the same period.  I did once spend a day analysing 5 years of scan results looking for variations in size and concluded that there was a stable trend and potentially a fading of one or two of my largest liver tumours. I was reminded these two types of scans were not really precise enough to detect small millimetre increases or decreases and as there were other factors at play, there was little commitment to make this declaration.  However, I did note in the summary of the CLARINET study, Lanreotide was associated with prolonged progression-free survival among patients with advanced, grade 1 or 2 (Ki-67 <10%) enteropancreatic, somatostatin receptor–positive neuroendocrine tumours with prior stable disease, irrespective of the hepatic tumour volume.  In terms of its anti-proliferative effects, an interim report from the CLARINET extension study suggested longer-term Lanreotide treatment is well tolerated with ‘anti-tumour’ effects in patients with progressive disease.  The final CLARINET open label extension study report additionally provided evidence for long-term PFS benefits of Lanreotide Autogel 120 mg in patients with indolent pancreatic and intestinal NETs.

There’s currently a trial ongoing in relation to Lanreotide and Lung NETs – read by clicking here.

I have my ups and downs and I do feel quite well most of the time.  Most people tell me I look quite well too – lucky they can’t see my insides!  Over the last 7 years, I’ve made some fairly significant adjustments to cope with my condition and maintain a reasonable quality of life – my monthly injection of Lanreotide is no doubt playing a big part.

Finally, please spend 5 minutes watching this fascinating video from Ipsen.  It explains in easy terms how Lanreotide works.  It also has a useful summary of the side effects at the end.  Click here to watch the video.

I’ve just been enrolled onto a new service called HomeZone whereby the injection is now administered at my home via an Ipsen provided and funded nurse.  Read here to see if you can also take advantage of this service.

THE SOMATULINE ‘RESERVOIR’ FORMING IN THE DEEP SUBCUTANEOUS TISSUE

In July 2018, I received my 100th injection of Somatuline Autogel (Lanreotide).  I was very grateful to still be here so I thought it was worth a celebratory cake – injection themed!

Cake with Needle

CAKE PHOTO1 WITH NURSE2

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Ronny

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Remember ….. in the war on Neuroendocrine Cancer, let’s not forget to win the battle for better quality of life


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