One injection of $2.1 million, those things about Zolgensma, novartis' most expensive drug with tacit approval from Chinese clinics

Text/Forbes China

Image source: Novartis China official website

On January 20, news spread rapidly about Novartis' sky-high drug Zolgensma being clinically licensed in China. "13 million a shot, the most expensive drug in history" attracts countless eyes.

In fact, as early as January 7, the Information Disclosure Center of the Drug Evaluation Center (CDE) of the State Food and Drug Administration of China showed on its official website that Novartis's AAV gene therapy drug Zolgensma (OAV101 injection) submitted a clinical trial application in China for the treatment of spinal muscular atrophy (Spinal Muscular Atrophy, SMA) has obtained implied clinical trial licenses. Previously, on October 21, 2021, the clinical trial application submitted by the drug was accepted.

According to Novartis, Zolgensma is a gene therapy based on adeno-associated viral vectors for the treatment of children under 2 years of age with spinal muscular atrophy (SMA) and bialelectrole mutations in the survival motor neuron 1 (SMN1) gene, which can prevent disease progression by continuously expressing the SMN protein by a single intravenous (IV) injection.

Zolgensma, whose intellectual property is originally owned by AveXis, in April 2018, pharmaceutical giant Novartis announced that it had acquired AveXis, a U.S. gene therapy company, for $8.7 billion in cash, bringing Zolgensma under its wing.

In May 2019, Zolgensma was approved by the FDA for marketing, which was the first and only gene therapy approved by the FDA at that time to treat SMA (spinal muscular atrophy), which is a gene therapy drug based on AAV vectors. Its approval accelerated the development of AAV technology.

Because Zolgensma is the world's first SMA disposable gene therapy, priced at $2.125 million, it has been called "the most expensive drug ever."

According to Novartis' financial report, Zolgensma's sales reached $920 million in 2020, an increase of 151% year-on-year, and sales in the first half of 2021 were $634 million, an increase of 69% year-on-year, according to this increase, Zolgensma is expected to enter the "$1 billion club".

In November 2020, the official website of Nature Biotechnology found that a study of adeno-associated virus (AAV) gene therapy published on November 16 found genomic changes that may increase the risk of liver cancer.

The findings have once again sparked controversy over gene therapies. Gene therapy is one of the most sought-after innovative treatment platforms in the industry, and viral vectors are currently the most popular delivery methods for gene therapy trials. Among them, AAV gene therapy vectors have been widely used in a number of basic studies and clinical trials because of their safety and efficacy.

After Zolgensma went public, it was not all smooth sailing. Just two months after Zolgensma was approved for marketing, in July 2019, the U.S. FDA accused Novartis of manipulating preclinical data that backed up its initial application. Subsequently, Novartis issued a statement saying it was "fully confident in the safety, quality and efficacy of Zolgensma."

In the end, the U.S. FDA did not sanction Novartis or revoke Zolgensma's listing qualifications, but the controversy led novartis to fire 5 top scientists within the team. A number of insurance companies in the United States refused to provide relevant insurance services for SMA patients aged 2 years and under according to the indication coverage of the drug, and instead limited the age coverage to infants under 6 months of age.

But Zolgensma's clinical approval is still exciting news, and if it is finally listed, it will benefit patients.

Spinal muscular atrophy (SMA) is a rare autosomal recessive hereditary neuromuscular disorder manifested as debilitating muscle atrophy and weakness. Children with SMA are predominantly infants and may present with hypotonia, poor head control, "frog leg" posture, dyspnea, developmental delay, scoliosis, or joint contractures. As the disease progresses, motor function gradually decreases.

SMA is the leading genetic factor in the death of infants under two years of age, severely affecting the quality of life of patients and caregivers, and patients have previously faced the dilemma of not having access to drugs.

According to the rare disease-related research report released by IQVIA, as of October 2020, there are still 16 drugs that have been listed in the mainland for the treatment of 14 rare diseases, which have not yet been included in the national medical insurance list, including 5 special drugs that cost more than one million yuan a year, and SMA treatment drugs are among them.

At present, 3 SMA therapies have been approved worldwide, all of which have been approved in China. They are Zolgensma, Spinraza by Kubojian, and Evrysdi by Roche.

Spinraza (Northinacine sodium injection) was approved by the State Food and Drug Administration in February 2019 for the treatment of 5q spinal muscular atrophy (accounting for about 95% of all SMA cases), which is also the first drug approved to treat SMA in China.

Previously, Spinraza was priced at nearly 700,000 bottles in China, requiring repeated injections every year and being a completely self-funded drug.

In the past decade, the exploration mode of medical protection for rare diseases at the local level in the mainland, whether it is major illness insurance, special funds or commercial supplementary insurance, has rarely included the medication of SMA patients in the protection of rare diseases. But that is gradually changing.

In December last year, at the China Rare Disease Conference, it was revealed that more than 60 rare disease drugs in China were approved for marketing, of which more than 40 have been included in the national medical insurance drug list, involving 25 diseases, including frostbite, hemophilia and so on.

According to the statistics of the Pain Challenge Foundation, as of December 3, 2021, based on the national "First Rare Disease Catalogue", there are 87 kinds of drugs for rare disease indications clearly registered in the mainland, involving 46 rare diseases; as of 2021, after the national medical insurance negotiations, 58 drugs with 28 rare diseases have been included in the national medical insurance list.

In 2021, a new round of medical insurance catalogue adjustment included more rare disease drugs, and a total of 7 rare disease drugs were successfully negotiated, with an average price reduction of 65%.

At present, the drug research and development of rare diseases has received attention, and more and more global multi-center clinical phase III drug trials have landed in China, and more drugs have been used for the treatment of rare diseases.

Healthy China, no one can be less.