(Health Times reporter Tan Qixin)
On January 20, the news that "the world's first spinal muscular atrophy (SMA) disposable gene therapy Zolgensma was tacitly approved by the Drug Evaluation Center of the State Food and Drug Administration" attracted attention, which also means that this "world's most expensive therapy" may land in China. However, the sky-high price of 13.48 million yuan makes patients unable to use it directly.
Healthcare workers treat SMA patients. Xinhua News Agency reporter Guo Xulei/Photo
The breakthrough therapy that patients desperately need is at least about 3 years away from being approved for marketing
Yang Guang is the father of a child with spinal muscular atrophy (SMA). Since october 21 last year, Zolgensma submitted a clinical trial application was accepted by the Drug Evaluation Center of the State Food and Drug Administration, Yang Guang has been paying attention to the progress in real time, "Not only me, many patients are paying attention, I don't want to help my child apply to participate in clinical trials for the first time." Yang Guang told the Health Times reporter.
According to the rare disease group data of the Science Branch of the Chinese Medical Association, SMA is a rare autosomal recessive neurodegenerative disease, which is divided into four types according to the degree of deterioration of motor ability: type 1 (infant type), type 2 (intermediate type), type 3 (adolescent type) and type 4 (adult type). In the absence of medical intervention, some critically ill patients can't survive their 2nd birthday.
According to the data of the Chinese journal of prenatal diagnosis, "Advances in molecular diagnosis and screening of carriers of spinal muscular atrophy", the incidence of SMA in newborns is about 1/6000 to 1/10000, which is equivalent to one in every 10,000 newborns affected by this.
Up to now, a total of three SMA therapeutic drugs have been approved for marketing worldwide, namely Novartis Zolgensma, Bojian's Neucinasin sodium injection and Roche's Risdiplam oral solution, of which the latter two have been approved for mainland listing.
Yang Guang's child is the most serious and common type I SMA, but the family has always been reluctant to give up, through the fight for assistance and medicine, has been injected into the child with 7 injections of Nosinasin sodium injection, according to the plan, 3 injections per year in the future.
"Zolgensma only needs one injection to take effect." My child is still so young, there is still so much in my life, what parent does not want the child to have a one-time cure? Yang Guang told the Health Times reporter.
According to Novartis' official website, Zolgensma is a gene therapy based on adeno-associated virus vectors, which is suitable for the treatment of children under 2 years of age with spinal muscle atrophy and survival motor neuron 1 gene bialelectrole mutations, and continuous SMN protein expression through a single intravenous injection can prevent the progression of the disease and thus solve the genetic root of SMA.
Data released at the 7th European Congress of Neurology in 2021 show that Zolgensma treatment data contrast significantly with the natural history of type 1 SMA disease, which, if left untreated, usually dies or undergoes permanent ventilation at age 2. New data from the Zolgensma3 SPR1NT clinical trial show that 100% of pre-treated SMA children achieved event-free survival, were independent of respiratory and nutritional support, achieved a primary endpoint of sitting alone for ≥30 seconds, and did not have serious treatment-related adverse events.
"At present, Zolgensma has only entered the stage of implied permission for clinical trials in the mainland, according to the normal procedure, from the recruitment of local participants to the end of the Phase 3 clinical trial, there are still many uncertainties, whether it can be approved for listing, depends on whether the final pharmaceutical company can hand over a clinical trial answer sheet that can prove the safety, quality and efficacy of the drug, according to the normal procedure inference, even if everything goes well, it will take at least about 3 years from being approved for listing." A senior drug developer, who did not want to be named, told reporters.
The world's most expensive drug, many countries explore innovative payment methods
In fact, the three SMA drugs currently approved for marketing are very expensive, in addition to Zolgensma, Northinasin sodium injection and Risdiplam oral solution were also regarded as "sky-high drugs" at a price of hundreds of thousands of dollars at the beginning of the market.
Officially approved for listing in the United States in May 2019, Zolgensma was priced at $2.125 million, dubbed the "world's most expensive drug" as soon as it was launched. Neucinasin Sodium Injection, which was approved for marketing as early as December 2016, is the world's first precision targeted SMA therapy drug, priced at $750,000 in the first year and $375,000 per year thereafter; Risdiplam oral solution is the world's first oral SMA treatment drug, according to the daily frequency, patients need to pay up to $340,000 per year.
However, in the 2021 medical insurance negotiations, Nocinasin sodium injection has taken the lead in entering the mainland national medical insurance directory through a sharp price reduction, from 700,000 a shot to 33,000 a shot, and finally the patient pays about 10,000 yuan / needle, achieving a breakthrough of zero of "sky-high drug into medical insurance".
According to Novartis official sources, Zolgensma has been approved in nearly 40 countries and regions around the world. At present, there are many innovative payment mechanisms for such innovative medical technologies or pharmaceutical products in the world, such as advanced therapies such as cell therapy and gene therapy that need to pay a high fee at one time, often using the "annuity system" method of installment payment, in the United States, Novartis and related insurance companies, the patient's family does not need to pay zolgensma in one lump sum, but can pay the cost in installments for 5 years, an average of 425,000 US dollars per year; another such as the "risk sharing" payment mechanism, under this mechanism, If the clinical efficacy does not achieve the expected effect, the pharmaceutical company needs to bear part of the drug cost.
Whether it can eventually be included in mainland medical insurance is still unknown
At present, many countries have also included Zolgensma in health insurance. For example, Zolgensma was included in Japan for public health insurance in May 2020, and patients only need to pay 30% of the fee; in November 2020, Italy decided to include Zolgensma in the list of drugs allocated by the National Health Service, and patients can be reimbursed through the Italian social security SSN; in March 2021, Zolgensma was included in the national health service system in the United Kingdom.
On the mainland, Zolgensma is actually too early to enter medical insurance. The above-mentioned senior drug developers, who did not want to be named, told reporters that for a drug to enter medical insurance, it must further collect "real-world evidence" in the clinical application process after being approved for listing, and submit it to the medical insurance department.
Xuan Jianwei, director of the Institute of Medicine of Sun Yat-sen University, believes that emerging cell therapy/gene therapy is generally more expensive, and even if such a sky-high drug lands, whether it can eventually be included in mainland medical insurance is still a huge unknown. "I think it is more appropriate to regard the results of the successful negotiation of rare diseases in last year's medical insurance negotiations after a sharp price reduction, and the final successful negotiation is regarded as a case, which means that there will be innovative drugs of the same price that will be included in the medical insurance in the future." Because in the case of rare disease drugs or innovative drugs that have just been launched, can manufacturers withstand the same reduction as Northina sodium injection? It still takes time to prove. ”
"For emerging treatment methods such as cell therapy/gene therapy, I am more inclined to encourage them to explore suitable and innovative payment methods for their own positioning and characteristics, rather than just crossing the one-way bridge of medical insurance." Xuan Jianwei said.