I am glad to be able to discuss an issue that I have been working on closely with my constituent, Ms Amarjit Rai. This is an urgent matter and I believe it is important to put this issue on public record and to seek greater flexibility in NHS policy on the commissioning of the drug Maraviroc to treat Natalizumab-induced progressive multifocal leukoencephalopathy, and in NHS England’s approach to individual funding requests. I thank Amarjit, her advocate, Kartik, her consultants and Mary Jo Bishop and Neha Soni in my office, as well as the House of Commons Library, for their assistance with this debate.
In my work on this case, I have been struck by parallels with the campaigns by the late Dame Tessa Jowell on the more experimental use of drugs for very rare conditions, for which there will never be the sample sizes in one country, or potentially across the world, for a full clinical trial, but for which the anecdotal evidence is positive and the patient voice should be heard. Some of my contribution today will be slightly technical, but I hope it will be clear.
Ms Rai was sadly diagnosed with multiple sclerosis in 2013 aged 34. She was prescribed Natalizumab, but sadly as a consequence she contracted PML, a highly rare and often fatal viral disease that affects only a handful of people across the UK. She has since been rendered disabled with no functional use of her right arm. She has other debilitating effects. PML affects the brain by damaging the nerves. The symptoms include muscle weakness, visual disturbance, impaired speech and cognitive difficulty.
I thank the hon. Lady for bringing this matter to the House. Does she agree that the treatment of this often fatal viral infection of the brain must be focused on survival rates and that, given that survival rates are better with Maraviroc, it must be available where clinically determined? If it is key to making lives better and halting this disease, we must do everything we can to make it available.
The hon. Gentleman makes a point that I will come on to about how the decisions need to be made on the medical evidence and with the voice of the consultants being clearly heard by those making the decisions.
There is no cure for this condition, but two years ago my consultant’s neurologist advised that Maraviroc had had a positive effect on patients suffering from PML in relation to her condition, immune reconstitution inflammatory syndrome in multiple sclerosis. An individual funding request was submitted by my constituent’s consultant, national expert Professor Ciccarelli at the National Hospital for Neurology and Neurosurgery. The application was refused and a subsequent appeal was also unsuccessful—this process went on through 2017 and 2018—seemingly on the same basis as was given to me in writing in October by NHS England, which was that the
“use of Maraviroc for this condition is currently seen as experimental as the current evidence is limited to very small observational studies. NHS England has concluded that there is not sufficient evidence to support the routine commissioning of this treatment for the indications listed.”
The effect on Amarjit was heartbreaking. I met Amarjit and her friend and advocate Kartik. She had a wheelchair and a walking stick, and even the most basic activities were a struggle. She had decided to fund the drug privately from her savings. Maraviroc had remarkable results for her—importantly, that was also the opinion of her consultants—without any side effects. Other treatments that the NHS had sought to prescribe, such as MRIs and monthly steroids, were not just neutral but net negative. Amarjit and Kartik explained the impact that Maraviroc had had on Amarjit’s health and quality of life. I was just staggered when she told me:
“I can talk. I can walk. I can go to the bathroom on my own”— things that we take for granted. Clinically, the PML lesion appeared inactive and there was a reduction in the inflammation around her brain.
The drug costs around £480 a month, but by the end of June this year Ms Rai could no longer afford to pay for it herself, so she has since been without it. Although her health has been stable so far, such is the condition that it could dramatically change at any time.
Aside from the issue of funding, I have been surprised over the past year by inconsistencies in NHS policy and advice. We all believe in an NHS that is free at the point of need. This is a situation where the patient, leading neurologists and all involved in her care agree that she should have the drug. In November 2018, consultant neurologist Dr Michael Gross, who was also supporting Amarjit’s care as an expert advocate, wrote to Kartik:
“Thank you for confirming further information about Amarjit Rai... Professors Johnson and Ciccarelli agree that this is the appropriate treatment for Amarjit. Long term steroids have already generated severe osteoporosis in 2016 and are not her choice.
You will have already proved in what is an N=1 trial that her treatment would appear to be effective. There will almost certainly never be the size of trials in this rare disorder that would allow a definitive statement by a funding organisation.
I think we have to ask who is making the decision, given that there are now three senior consultants confirming this is the right decision…
Quite frankly I am appalled by the lack of humanity that is being demonstrated here.”
“Maraviroc is not licenced for the treatment of symptoms of PML. There are clinical situations when the use of unlicensed medicines or use of medicines outside the terms of the licence, known as off-label, may be judged by the prescriber to be in the best interest of the patient on the basis of available evidence. The responsibility for that falls on healthcare professionals.”
Sadly, this made no difference.
Following the lack of progress, I wrote again to the Secretary of State in March 2019. I quoted the helpful response that I had received from Lord O’Shaughnessy. The Health Minister in the other place, Baroness Blackwood, responded in May and referred again to the individual funding request process. She stated that the IFR can be considered only if the patient can be demonstrated to be clinically exceptional. She said that
“an IFR can only be considered if the patient can be demonstrated to be clinically exceptional compared to the wider group of patients and is likely to derive greater benefit from the treatment.”
At face value, all of this would appear to be true for my constituent, but the use of Maraviroc is an area where policy appears to be in some confusion.
In response to a parliamentary question I asked in July about the assessment that NHS England has made of the availability of Maraviroc to patients with PML, a third Health Minister, Seema Kennedy, wrote:
“We are informed by NHS England and NHS Improvement that it does not commission Maraviroc for progressive multifocal leukoencephalopathy…
NHS England and NHS Improvement have published a do not commission policy for ‘Natalizumab-induced progressive multifocal leukoencephalopathy in relation to immune reconstitution inflammatory syndrome in multiple sclerosis.’”
That response seems to contradict earlier responses and advice. First, “does not routinely commission” is different from “does not commission”. Secondly, it made no reference to the IFR process, which two Ministers had previously mentioned.
I tabled a further parliamentary question last week to ask what assessment the Secretary of State had made of the effectiveness of Maraviroc in patients with PML. A fourth Health Minister, the Under-Secretary of State for Health and Social Care, Ms Dorries, responded to my question. The response I received today was mind-boggling:
“Maraviroc is currently authorised for the treatment of patients who are infected with HIV type 1. The Medicines and Healthcare Products Regulatory Agency which is responsible for the regulation of medicines in the UK is not aware of any application for use in patients with PML and therefore cannot comment on the efficacy of this drug in patients with PML.”
It might be helpful if I highlight for the Minister findings from wider medical journals that the House of Commons Library has helped me to compile. In December 2016, the American Academy of Neurology published an article entitled “Severe early natalizumab-associated PML in MS: Effective control of PML-IRIS with maraviroc”. A summary of a case involving a 55-year-old Caucasian HIV-negative man diagnosed with relapsing, remitting MS in 2013 shows that that led to a subsequent diagnosis of PML. Clinically, the patient deteriorated rapidly, according to the article. Oral Maraviroc was initiated six days after his admission. Eight days after Maraviroc initiation, MRI follow-up revealed stable PML lesion size. Over the following weeks, the patient improved continuously. After 25 weeks of Maraviroc treatment, the John Cunningham virus DNA was no longer detectable. Maraviroc was continued and well tolerated at a stable dose. The patient survived both PML and IRIS.
A subsequent article was published by the American Academy of Neurology entitled “Maraviroc as possible treatment for PML-IRIS in natalizumab-treated patients with MS” in December 2016. It cited a 34-year-old man treated with Natalizumab for three years without previous immuno-suppression. After a period of time, the patient was admitted with seizures, headaches, and impaired memory, and an MRI scan subsequently confirmed PML. Twelve months after diagnosis with PML and six months after the start of Mariviroc, PML-IRIS lesions were resolved, and no new MS disease activity was detectable.
An article in 2017 by Steiner and Benninger published by the American Academy of Neurology built the medical explanation for why Maraviroc had been effective in cases of PML in MS sufferers. In summary, the condition for which the cause is believed to be the John Cunningham virus, which infects the central nervous system in patients with low immune conditions, became more prevalent and was observed in around 5% of patients with HIV prior to the availability of highly active antiretroviral therapy, or HAART. The article goes on to describe how the era of
“monoclonal antibodies for immune-mediated conditions such as Natalizumab for MS and Crohn disease heralded another context for PML. As of November 2016, there have been 698 reported cases of PML under natalizumab.”
The research goes on, and it is true that some research such as that published in The Journal of the Neurological Sciences in July 2017 confirms that it does not work in all circumstances, and steroids may be more effective in some patients. However, an article in Neurology Times in January 2018 states that in PML treatment options are limited. Maraviroc has been used successfully in some PML patients to avoid IRIS, although not all patients respond to Maraviroc. It recommends further research and testing in identifying patients at risk of IRIS and tailoring treatments accordingly.
In that context, let me make reference to the urgent clinical commissioning policy statement on Natalizumab-induced PML, which was published by NHS England in March 2018. It said:
“It has been assessed that the development of a full policy is not needed at this time as there is currently little evidence into its effectiveness for this indication”.
I do not believe that that policy statement takes account of all the research available or indeed that which has appeared subsequent to its publication. The research is more nuanced, the medical benefits for my constituent are undeniably clear, and the denial of funding is inexplicable to her and renowned experts in the country.
Maraviroc, or Celsentri, as defined by the European Medicines Agency—formerly in London, it is now based elsewhere in the European Union—is a medicine that is routinely prescribed for HIV. Although it does not cure HIV infection or AIDS, it may hold off the damage to the immune system and the development of other infections and diseases.
Medical research has identified that the JCV most associated with HIV patients with low immunity has found another context in patients with PML. My constituent’s condition is incredibly rare, affecting, potentially, 10 or fewer people in the country. Given that very few options are available, she is not the only patient for whom, in anecdotal studies, the drug Maraviroc has shown remarkable results. With no other options available, my very ill constituent has been paying £500 a month privately for the past year to fund Maraviroc herself, but she can no longer afford to do so. Amarjit’s consultant neurologist and other specialists support her receiving the treatment. There is an irony in the fact that more is potentially being spent by the NHS in a month on treatment and tests that do not benefit her as much, and have damaging side-effects. The IFR system in the NHS should be able to review and respond to that situation on the basis of medical need, and I cannot see how that has been done in this case.
Will the Minister tell me how her Department liaises with and challenges NHS England on cases such as this, and how well-researched the Department’s responses to me have been? Will she tell me with what medical advice the treatment has been refused, although three of the leading experts in the country support it in this rare case, and whether their advice can be shared with my constituent and her consultant, Professor Ciccarelli? Will she also agree to a meeting with me, my constituent and her consultant, and a senior member from NHS England to discuss the IFR process?
This is a matter of £500 a month, and of demonstrable medical benefits to my constituent. I should be grateful for the Minister’s response, and her advice on how we can move forward.
I thank Seema Malhotra for raising this matter in the House, and for the comprehensive and sensitive way in which she has set out problems that will certainly be well recognised by many patients—not only her constituent, but people throughout the rare disease community. A number of the issues that she has raised affect what are often very small cohorts trying to put their case for particular drugs.
As we have heard from the hon. Lady, progressive multifocal leukoencephalopathy is a terrible disease which can have devastating effects on patients whose immune systems are already impaired, often as a result of taking medicines. Maraviroc is an antiretroviral drug approved by the Medicines and Healthcare Products Regulatory Agency for the treatment of HIV. In this case, the hon. Lady’s constituent, who unfortunately has multiple sclerosis, has been paying privately for the drug, which I understand she feels has a positive effect on her condition.
The use of Maraviroc for people with MS is “off-label”. Medicines sold and supplied in the UK must, rightly, have a licence, which specifies the medical conditions that they are approved to treat, and also specifies the recommended doses, contra-indications, and special warnings as specified by the MHRA. All that is intended to ensure the safety of the patient. Off-label use, as I am sure the hon. Lady is aware, describes that situation where the licensed medicine is used for an indication other than that for which it is licensed originally. However, as she said, a decision to use a medicine off-label is one for the individual clinician. In each case, it is for that professional to make that decision if they think the treatment is appropriate for a patient and they are satisfied that there is robust evidence to support their prescribing decision.
As the drug in question is a licensed medicine for the treatment of HIV, not PML, it has not been fully tested with PML patients in clinical trials. Therefore, it has not been approved as safe and effective. Crucially, it is important to note that the use of this drug to treat Natalizumab-induced PML currently has an evidence base limited to small observational studies where no conclusive evidence of patient benefit was found. However, I fully appreciate that it is a real challenge to establish a clinical evidence base when the patient population is so small.
In fact, as the hon. Lady mentioned, NHS England and NHS Improvement were asked in 2018 to develop a commissioning policy on the use of Maraviroc for the treatment of Natalizumab-induced PML. They concluded, however, that there was insufficient evidence of benefit and advised against routine commissioning. Maraviroc is not currently appraised or recommended by national bodies for the treatment of PML, because there is a lack of evidence of effectiveness and a lack of any evidence-based clinical support in the treatment of PML. NHS England has therefore concluded that there is not sufficient evidence to support the routine commissioning of the drug—a conclusion that clinical commissioning groups are minded to follow. Of course, that position would be reviewed should further evidence become available.
Despite Maraviroc not being routinely commissioned by the NHS, it remains possible for patients to access the drug through the individual funding request, which, as the hon. Lady has said, her constituent did. An independent panel would have considered the circumstances of the request before making a decision. In this case I understand that the IFR was rejected, which I know would have been upsetting for the hon. Lady’s constituent. Following the outcome of the IFR, the reasons for the decision would, I am sure, have been explained to her constituent. If not, I urge the hon. Lady to ensure that they are explained in full.
I understand that this is a technical matter in some respects, but I am a little surprised that I have not heard the Minister say anything new compared with the responses I have received to parliamentary questions. I have laid out the evidence and shown that there are nuances. In the case of my constituent, the medical benefits have been clear. I am surprised that the IFR was denied, including subsequently on appeal, and, given that I have laid out the evidence, that the Minister is not in a position to give advice on how we can move forward so that we do not keep going around in circles.
I think that part of the confusion has come from the fact that the NHSE advice not to commission is different from the independent funding route process. Clinicians can always apply for IFR funding in exceptional circumstances. The MHRA parliamentary question was about availability. One offer I can make is that we will try to unpick those four answers and to understand a little more in the round how we can be of assistance and give the hon. Lady’s constituent clarity, if nothing else.
The Minister is very generous in giving way. Rather than restating the policy, will she support the request for the medical advice that was the reason for the treatment and funding being refused? There must have been some medical input into the decision made by the panel at NHS England. Will she also be able to meet me to review the process and what my constituent has been through? Clearly my constituent is in a very rare circumstance—she is possibly one of fewer than 10 people in the country—but surely we are able to work a bit faster and with more agility in a situation where, in a sense, the patient and the experts in the field should be leading.
I am, of course, happy to meet the hon. Lady, but we must be led by clinicians. As she says, her constituent has been supported by her clinicians, and it is up to them to make clinical judgments and to put the case for the best course of treatment in each particular case. The first thing to do is to seek clarification on where we know we are going, and hopefully we can move forward from there.
As the hon. Lady says, the PML group is around 10 in number, so getting robust evidence is obviously a challenge—that is all part and parcel of the issue. As she knows, another challenge is that the Department of Health and Social Care does not have direct responsibility for what is routinely commissioned. Instead, it is the responsibility of NHS England, NHS Improvement and the CCGs. Faced with an unprecedented level of demand for services, all those involved have to make difficult decisions about commissioning cost-effective care on a daily basis. They make those decisions based on patient need and clinical evidence, which I acknowledge can feel very cyclical for the rare disease community.
Does the Minister agree it is slightly more problematic in this case, because the cost of maraviroc is arguably a bit less than the MRI scans and the steroids every month that the NHS would otherwise prescribe or suggest to my constituent? The negative health impact of that treatment should also be taken into account.
I thank the hon. Lady, but I return to the fact that it is a judgment for clinicians to make; it is not one for me to make at the Dispatch Box.
My colleague Baroness Blackwood rightly said this summer that we need a national conversation on rare diseases to identify the big areas on which we need to focus so that we can offer the best possible care for rare disease patients and their families, who are often affected by what their loved ones are going through. I could not agree more so, starting this autumn, we will be engaging with patients, researchers and clinicians to gather evidence and identify the major challenges faced in this field.
I am not in a position to say. Although each cohort is small, the overall rare disease community is large. That is why such debates make an important contribution to the broader conversation. I am grateful for how they raise awareness of the rare disease community, which comprises some 3.5 million people in this country.
I will make this my last intervention. I just want to welcome the work that will be done in respect of the rare disease community. May I add to the comments in this House in welcoming the Minister to her place? I know that her experience will be extremely valuable in the work that she does in the Department.
I thank the hon. Lady sincerely for that and for speaking so passionately here today about the situation on behalf of her constituent. I know that her constituent may not feel that this is the answer that she wanted, but I cannot emphasise enough the positive effect of bringing this issue to the Chamber. Not only will it raise awareness, to help inform Government strategy, but it will support others in the rare disease community. As the hon. Lady said, allowing their voice to be heard is what is important here.
Question put and agreed to.