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Genetic medicine ($2.5m./injection) rewrites the fate of a 5-month-old baby!
Genetic medicine ($2.5m./injection) rewrites the fate of a 5-month-old baby! No longer “no medicines available”, but “some medicines are not available”
Arthur Morgan, who was only 5 months old, was named “No. 1” by many British media: Britain’s first baby to receive a “highly-priced drug” for spinal muscular atrophy (SMA).
Caption: Arthur Morgan/BBC
On the eve of “International Children’s Day” on June 1, news came from the Evelina Children’s Hospital in London, England. A week ago, Arthur injected the gene drug savaprevir intravenously in the hospital and is in good condition.
Sovaprevir is known as “the most expensive drug in the history of pharmaceuticals”. The price of each in the UK is 1.79 million pounds, about 2.5 million US dollar.
In March 2021, the drug was approved to be included in the UK’s National Health Service (NHS), paid by medical insurance, and used for SMA patients under 1 year old with a mutation in the motor neuron survival gene 1 (SMN1). The NHS said it reached a “milestone agreement discount” with drug manufacturer Novartis. The specific amount has not been announced, but it is “a fair price to taxpayers.”
“The doctor said that he has suffered some permanent neuronal damage. We don’t know what will happen in the future, but we will do our best to provide him with everything.” Arthur’s father Reece Morgan told the BBC.
Photo caption: Arthur Morgan and his father Reece Morgan (Reece Morgan, right). /BBC
SMA Type 1: Without treatment, you will not live to be two years old
Arthur was born in December 2020, a premature baby. During the parenting process, the parents found that their arms and legs were weak and unable to move independently. In early May 2021, Arthur was diagnosed with SMA type 1.
The “Clinical Practice Guidelines for Spinal Muscular Atrophy” shows that SMA is one of the most common lethal autosomal recessive diseases in infants and young children. It is caused by SMN1 mutations. The clinical manifestations are progressive, symmetrical, and proximal to the limbs. Mainly muscle weakness and muscle atrophy.
According to the time of onset and clinical phenotype, SMA is divided into 4 subtypes. Among them, SMA type 1, which develops within 6 months after birth, is the most common and most severe type. Children usually die within two years after birth. The cause of death is respiratory failure.
Type 2 onset occurs 6-18 months after birth and is a common cause of death during adolescence.
Type 3 develops after 18 months of birth. Children can walk independently in the early stages of onset, but they may experience repeated falls and difficulty going up and down stairs. With age, you will gradually lose the ability to walk.
Type 4 is an adult type, which usually develops after the age of 20 or 30. The patient has only slight movement disorders and the respiratory system is not affected. The life expectancy of type 3 and type 4 patients is normal.
The neonatal incidence of SMA is 1/10000-1/6000. “International Rare Disease Day” lists it as a kind of rare disease. There are data estimates that the population carrying rate of SMN1 mutant genes is about 1/72-1/47, which is racially different. If both husband and wife carry them, the probability of their children becoming carriers is 1/2, and the probability of illness is 1/4. If one spouse is a carrier, there is a 50% chance that the child will also become a carrier.
“It is a terrible thing to be diagnosed with SMA in infancy. Untreated children have a very short life. Once they become ill, they will gradually become unable to raise their heads, sit up or roll, and have difficulty swallowing and breathing. They need 24-hour care. “Jerry Mandel said. He is the principal investigator of the Gene Therapy Center at the Abigail Wexner Institute at the National Children’s Hospital in Ohio, USA. The center has participated in the clinical research of Sovaprevir.
Two kinds of medicines, they are both “much expensive.”
There are 4 NHS-affiliated medical centers in England and the United Kingdom, providing savaprevir treatment. Evelina Children’s Hospital in London, where Arthur is located, is one of them.
Elizabeth Reig, a consultant in pediatric neurology at the hospital, told the BBC that the earlier the SMA treatment intervention is initiated, the better the effect. But in the past few decades, hospitals have “no medicines available”, and the life expectancy of children with SMA is very short. “Now, many children are treated to sit, roll, crawl, and play on their own. Some children can even walk.”
Data show that Sovaprevir is the world’s first gene therapy to treat SMA. It carries a functional copy of the human SMN1 gene into an adenovirus vector, enters the human body through intravenous injection, and delivers it to the motor neuron cells in a targeted manner, so that the SMN protein is expressed in children’s motor neurons, thereby improving muscle movement and function, and prolonging Lifetime. The medicine only needs to be injected once.
On April 16, 2019, the Phase 3 clinical data of Sovaprevir was released. As of September 7, 2018, 21 test children survived without incident; of the 7 drug patients, 6 of them reached the age of 10.5 months or older. “Event” means death, or ventilatory support for at least 16 hours a day for 14 consecutive days. Moving forward, in 2017, the New England Journal of Medicine published an article stating that all 15 children who participated in the Phase 1 clinical trial had survived two years of age.
On May 24, 2019, Sovaprevir was approved by the U.S. Food and Drug Administration (FDA) for the treatment of SMA patients under 2 years of age with biallelic SMN1 mutations.
Ned Sharpless, then the director of the FDA, said that this breaks the “only drug” situation for SMA treatment and is another milestone in the transformation of gene and cell therapy.
As early as December 2016, the FDA approved the world’s first SMA treatment drug Noxinarine Sodium to be marketed. This puts an end to the plight of no medicine for SMA. In February 2019, Nocinasheng Sodium was approved to be listed in China. Its manufacturer, Biogen, said that the drug was approved by the National Medical Products Administration. It is based on data from more than 300 clinical studies involving infant-onset and late-onset SMA patients for the treatment of 5q spinal muscular atrophy (5q- SMA).
Novartis’ 2020 financial report stated that savaprevir has been approved in 37 countries to treat more than 800 children. 2020 is the first full financial year after its listing, achieving sales revenue of US$920 million, an increase of 150%.
As of December 31, 2018, there are more than 6,600 SMA patients in the world who have been treated with Noxinassen Sodium. Its sales in 2019 increased to 2.1 billion U.S. dollars.
In March 2021, GoodRx, a US drug price tracking website, announced a list of the top ten most expensive drugs. Sovarrevir topped the list with US$2.125 million each.
When Nosinagen Sodium was marketed in the United States, it was also known as the “sky price”: each injection costs approximately US$125,000. According to the instructions, the drug needs to be administered by intrathecal injection. Start treatment with 4 doses, where the first 3 doses need to be used every 14 days, and the fourth dose is used 30 days after the third dose. Thereafter, a maintenance dose was injected every 4 months. This means that the drug costs about 750,000 US dollars in the first year and about 375,000 US dollars per year thereafter.
“Orphan drugs” are generally expensive?
Taking stock of the “World’s Most Expensive Drug List” in recent years, it will be found that the related lists have been dominated by rare disease drugs and supplemented by new anti-cancer drugs over the years.
An orphan drug business model research report released by a British consulting company in 2019 mentioned: “The global orphan drug market is growing by about 8% (from $79 billion to $114 billion) each year, mainly due to the prognosis of serious or life-threatening diseases. The demand for drugs is huge, and the lack of competition has led to high prices. “Orphan drugs” refer to drugs used for the prevention, treatment and diagnosis of rare diseases.
Regarding the pricing strategy of savaprevir, “intellectuals” quoted Novartis’s official website to explain that it is about 50% of the total cost of SMA standard treatment for 10 years of 4.5 million US dollars.
“For patients and the entire medical system, the current pricing is more consistent with the interests of these children and their families. This is a positive result.” Steven Pearson, president of the Boston Institute of Clinical and Economic Review, in a statement Means in.
The price of a single injection of Nosinagen Sodium in the Chinese market is 699,700 RMB, which has dropped a lot compared to the first US market.
However, these two drugs are among the top pricing in the world and have been questioned by many parties. They are accused of far exceeding the financial affordability of ordinary families, and they are also huge economic pressures on medical insurance or government agencies.
“Intellectuals” issued a paper in 2019 pointing out that the above two drugs are “orphan drugs.” This market is small, and pharmaceutical companies are generally unwilling to invest resources in research and development, making the treatment of related diseases difficult.
In 1983, the U.S. Congress passed the Orphan Drug Act, giving R&D pharmaceutical companies many preferential policies, including free pricing power. This has greatly promoted the research and development of orphan drugs, and its pricing has reached an unprecedented “high”. For example, Myalept, developed by Aegerion, is an orphan drug used to treat systemic lipodystrophy. The patient uses about 10 doses per month, and each dose is priced at US$4,632, which means that the monthly treatment cost is US$46,320. The Cuprimine capsule for hepatolenticular degeneration is priced at more than US$260 per capsule and needs to be taken for life.
In addition, most drugs will usher in a large number of imitations after the patent expires, causing the drug price to drop sharply. However, the user population of orphan drugs is too narrow, and there are limited imitation manufacturers, and few manufacturers are even willing to imitate them. This also keeps prices high.
In order to improve the affordability and accessibility of savaprevir, pharmaceutical companies and governments are thinking of ways.
Novartis has launched an “installation payment” strategy that allows patients’ families to pay off the drug in five years. In addition, the payment is based on the results of the treatment, if there is no effect, the fee can be reduced.
Some countries include it in medical insurance. In addition to the United Kingdom, on May 13, 2020, the Ministry of Health, Labour and Welfare of Japan listed savaprevir as the applicable object of public medical insurance. It is suitable for SMA patients under 2 years old, and the price is 167.07 million yen (approximately RMB 11.02 million) . This is the highest price of medicines covered by medical insurance in Japan.
Bloomberg columnist Max Nissen commented that gene therapy is on the eve of the outbreak, and dozens of gene therapies that will be on the market are likely to use savaprevir as a reference to set prices. This may be a new challenge for the struggling medical insurance system of various countries.
(source:internet, reference only)