So, after 5 years (almost to the date), it is all about to be over and with that is a lot of fear and grief. Fear of the unknown, fear of how long I will continue to benefit from crizanlizumab and the grief of the improved quality of life that came with it all.
In Jan 2020, I became the second participant in the UK for Novartis's phase 3 STAND trial.
It was a double-blind trial (neither the participants nor the researchers know which treatment or intervention the participants are receiving), testing crizanlizumab 5mg/kg or 7.5mg/kg vs placebo.
It was an exciting time;
1. it was the first medication for sickle cell disorders (SCD) in decades
2. it was a medication trial that included multiple SCD genotypes e.g. HbSC, HbSβ⁰-thalassemia etc rather than only HbSS (also referred to as sickle cell anaemia, I wish we wouldn't!).
This is why I jumped at the chance to be a part of the trial. That, and I had begun my blogging journey and was becoming ever more aware of just how few people including healthcare professionals know about SCD.
After about 18 months of being on the trial, the number of A&E hospital visits and admissions had dwindled and was down to zero. Before Jan 20 I was averaging 2 - 3 admissions annually and several other A&E visits that did not lead to admissions. My fibromyalgia symptoms and general immune system also saw significant improvements. It was amazing. It changed my quality of life in a way I could never have imagined, reduced health anxiety, improved ability to do more spontaneous activities and trips out etc. It was incredible.
I think I knew then that I was probably on the drug however, lots of others were also seeing improvements. You see usually people engage with their haematology teams once or twice a year unless they are admitted so the increase in the touch points meant more and better direct care and discussion about people's SCD. This in and of itself will improve people's symptoms and concerns, so is an additional positive on taking part in the trial.
In Dec 22 it was confirmed that I was on crizanlizumab 5mg/kg dose which was amazing news, and I continued this dose and on the trial. THEN... in Jan 23 Novartis announced the preliminary results from the global STAND trial indicated no statistically significant difference between crizanlizumab 5mg/kg or crizanlizumab 7.5mg/kg and placebo with regards to the annualised rates of VOCs, also known as pain crises leading to a healthcare visit over the first-year post randomisation. These findings were inconsistent with previous trial results from SUSTAIN which demonstrated the superiority of crizanlizumab 5.0mg/kg compared to placebo. The safety profile of the drug remained consistent with the commercially available dose.
Summary of the trial findings:
SUSTAIN - Found to reduce the annual rate of VOCs by 45%. Novartis also reported that more than one-third of patients did not experience a VOC while taking Criz. Additionally, patients were hospitalised for fewer days over the course of a year, showing a 42% reduction in comparison to patients treated with placebo.
The SUSTAIN trial results led to crizanlizumab being approved by the FDA in November 2019 and in October 2020, the European medical agency (EMA) granted conditional marketing authorisation to prevent recurrent VOC in patients aged 16 years and above, living with SCD.
Let's break this down: (Phase 2 = SUSTAIN : Phase 3 = STAND)
1. phase 2 - Americas only : phase 3 - GLOBAL
2. phase 2 - 5.0mg/kg + placebo : phase 3 - 5.0 + 7.5mg/kg + placebo
3. phase 2 - delayed the time to first sickle cell pain crisis (SCPC) in patients vs placebo : phase 3 - measured annualised rates of VOC vs placebo
4. phase 2 - pre-covid : phase 3 - during start and height of covid
For me the key differences in the results of STAND versus the previous study are caused by multiple factors, namely the wide geographical differences in the cohorts and the impact this has on how healthcare is utilised and accessed. Followed by covid and the low VOC rates in all arms of the study, possibly due to the selection of pts with generally less severe symptoms, or, due to the lower reporting of VOCs during covid due to other issues superseding this.
In May and June 23, I was selected as the patient representative at the EMA and the Medicines and Healthcare products Regulatory Agency (MHRA) to discuss my experience on the trial and to answer any questions. I was particularly disappointed at the discussions during the EMA discussion. I think it catches people out when they discover that I'm not only a patient but a healthcare professional with a background in A level Science education meaning my knowledge extends past my personal experience and includes scientific and research knowledge also...
In January 24, the MHRA revoked the license for Crizanlizumab and by the end of Feb it was recalled from pharmacies across Europe including in the UK. Since then the other treatments that were either being trialled or awaiting approval from NICE were withdrawn. Voxelotor - was withdrawn voluntarily by Pfizer due to due to safety concerns
So, what next?
To be honest, for me? Nothing. I could use the medication that is existing and has been around for decades, but it is a chemo drug and it raises your haemoglobin level but mine is normal so taking it would mean additional touch points with healthcare for exchange transfusions etc to bring my haemoglobin level back in line. The potential side effects of the medication are as you would imagine are hair loss, increase in infections (due to impact on bone marrow etc) and nausea, just to name a few. The only other option is prophylactic red cell exchanges which is used to remove the damaged (sickled) red blood cells and replaces them with donated healthy ones. My main fear is the loss of quality of life I have gained over the last 5 years. I've been fortunate to have been so positively impacted by crizanlizumab and I will grieve the loss of it at the end of the month when I go in for my final infusion...
For now, I have to hold strong and just be so incredibly grateful for the positives being the longest STAND trial participant in the UK has provided me, not just from the medication but also from the opportunities.
Did you know?
- SCD is currently the fastest growing genetic disorder in the UK
- persons with haemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease.
References
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