A new oral treatment combination for multiple myeloma, a treatment option for some adults with hereditary transthyretin-related amyloidosis (hATTR), and gene therapy for Duchenne muscular dystrophy, make up a hat-trick of approvals from the National Institute for Health and Care Excellence (NICE).
Around 2000 people with relapsed or refractory multiple myeloma are set to benefit from ixazomib, in combination with lenalidomide and dexamethasone, following final draft NICE guidance, which means "fewer hospital trips for vulnerable patients", said NICE.
Ixazomib citrate (Ninlaro, Takeda) is a proteasome inhibitor and has been recommended, in combination, for people who have already had two or three treatments. NICE pointed out that the new combined treatment regimen will be the "only oral triple therapy for people at this stage of the treatment pathway".
Treating Multiple Myeloma Becomes 'More and More Challenging' with Each Relapse
NICE explained that treating multiple myeloma becomes "more and more challenging" with each relapse, and treatment side effects and frequent hospital visits can have a major impact on people. "Oral treatment regimens reduce pressure on hospital outpatient units and chemotherapy day units, compared with intravenous options, and are very important to people with multiple myeloma," it said. In addition, fewer hospital visits also reduce the risk of acquiring infections.
"Scientific evidence suggests that people with multiple myeloma who have this treatment live longer before their disease gets worse, compared with people who have the standard treatment of lenalidomide and dexamethasone," said NICE.
The NICE committee concluded that ixazomib combination is a cost effective treatment for people with relapsed or refractory multiple myeloma and so it is "recommended for routine use in the NHS", it said, provided that the company provides ixazomib according to the commercial arrangement.
Shelagh McKinlay, Myeloma UK's director of research and advocacy, said that the treatment combination was a "game-changer" and that the charity was "absolutely delighted" with NICE's decision. "It gives patients something they could only have dreamed of just a few years ago," she said, "a life that doesn’t revolve around weekly hospital appointments".
Prof Graham Jackson, consultant haematologist at Newcastle Hospitals NHS Foundation Trust and professor of clinical haematology at Newcastle University, said that it was "fantastic news" for myeloma patients.
He expressed it was an important "triplet therapy" that gave an average of 6 months longer in remission and was effective in both low- and higher-risk disease. "It is the only triplet therapy that is all oral, meaning patients have to spend less time in hospital receiving treatment," he reiterated.
Rare Inherited Liver Condition Treatment More Cost-Effective
NICE has also issued final draft guidance which recommends vutrisiran (Amvuttra, Alnylam Pharmaceuticals) as an option for some adults with hereditary transthyretin-related amyloidosis (hATTR).
hATTR is estimated to affect around 150 people in the UK, and is a progressive condition that causes the liver to produce abnormal transthyretin protein. Deposits of transthyretin form in the tissues of the body (amyloidosis) and these can disrupt the structure and damage the function of the affected tissues.
Over time, these deposits can cause symptoms of polyneuropathy and of cardiomyopathy. In some cases, the autonomic nervous system may also be affected by amyloidosis.
Vutrisiran is an RNA interference (RNAi) therapeutic that inhibits the production of disease-causing transthyretin (TTR) protein by the liver, leading to a reduction in the level of TTR in the blood. It is administered by subcutaneous injection every 3 months.
NICE already recommends patisiran and inotersen as treatment options for stage 1 and stage 2 polyneuropathy. NICE explained that the benefits and costs of vutrisiran were compared with those of patisiran, and that analyses suggested vutrisiran works as well as patisiran. In addition, because it is administered every 3 months, compared with patisiran’s administration by infusion every 3 weeks, it costs "significantly less per patient".
Vutrisiran costs £95,862.36 per injection, and at the recommended dose the estimated annual cost per patient is £383,449.44. The company has a confidential commercial that makes vutrisiran available to the NHS with a discount.
NICE said that vutrisiran is recommended as an option for treating hereditary transthyretin-related amyloidosis in adults with stage 1 or stage 2 polyneuropathy, so long as the company provides the drug according to the commercial arrangement.
'Nonsense Mutation' Bypassed
Duchenne muscular dystrophy gene therapy ataluren (Translarna, PCT Therapeutics) has been recommended by NICE for routine NHS funding in final draft guidance.
Usually affecting only boys, Duchenne muscular dystrophy results from a lack of the protein dystrophin. There are between 60 and 70 children born with the condition in England each year, and in around 1 in 8 (13%) children it is caused by a 'nonsense mutation', explained NICE.
Current treatment options for patients with Duchenne muscular dystrophy in England are "limited" and aim to alleviate symptoms and manage complications. The standard treatment is corticosteroids, which NICE pointed out can delay deterioration but can cause unwanted effects such as growth retardation, bone thinning, mood swings, and weight gain.
Ataluren is the first licensed treatment for Duchenne muscular dystrophy that addresses the loss of the protein dystrophin and works by allowing the body to "read over" the nonsense mutation in the DNA and continue to produce the protein.
NICE said that scientific evidence, and feedback from clinicians and patients, suggested that ataluren is likely to "slow down disease progression" and delay the time at which the ability to walk is lost. They added that ataluren may also improve outcomes - such as preventing scoliosis and maintaining upper body strength - once the ability to walk has been lost.
However, they warned that evidence for improvements in later stages of the disease and improved survival with ataluren is "limited and highly uncertain".
The list price for the therapy is around £220,000 per patient per year.
NICE said that having considered the evidence, and together with an improved commercial arrangement agreed with the company, it felt the cost-effectiveness estimates for ataluren were "within the range" it usually considers acceptable for highly specialised technologies.
Therefore, it recommended ataluren, within its marketing authorisation, as an option for treating Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene in people 2 years and over who can walk.
Muscular Dystrophy UK said that the decision will be "warmly welcomed by all who have been involved", and reassured that the decision by NICE would mean that "new patients will now be able to receive the treatment, as well as those already receiving it".