Biogen's Spinraza, Fosun Kite's Yescarta and a controversial Alzheimer's drug: All you need to know about China's new state coverage

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Now, after a third year without a deal, China’s national reimbursement drug list path seems to be a dead end for foreign PD-1/L1 inhibitors such as Merck’s Keytruda, Bristol Myers Squibb’s Opdivo and AstraZeneca’s Imfinzi. (Getty Images)

It’s that time of year again when biopharma companies cut the price of their drugs to win national coverage in China.

Sixty-seven novel therapies entered China’s national reimbursement drug list (NRDL) for the first time and offered an average 61.7% discount through negotiations with the government, the country’s National Healthcare Security Administration unveiled (Chinese) Friday.

Biogen’s spinal muscular atrophy therapy Spinraza and Pfizer’s heart drug Vyndamax are among pricey rare disease drugs that are included for coverage starting next year. By comparison, Fosun Kite’s newly approved CAR-T therapy Yescarta as well as PD-1/L1 inhibitors by Merck & Co., Bristol Myers Squibb and AstraZeneca all failed to secure a place on the updated list. Here, we compile some of the most notable movements from this round of NRDL.

Rare disease drugs make history

Before the NRDL negotiations kicked off last month, Biogen’s Spinraza had found itself at the center of the public spotlight in China thanks to a widely reported medical bill linking the spinal muscular atrophy infusion to over 550,000 yuan (about $86,000) in total hospitalization cost during a four-day stay for a 1-year-old child.

Spinraza entered China in 2017 at about 700,000 yuan per injection. The drug is given three times a year after the initial loading doses. Since its launch, though, patient assistance programs in place for Spinraza have meant the price can be lowered to about 550,000 yuan per year, according to local media reports.

Chinese authorities haven’t disclosed the exact reimbursement prices of the drugs on the latest NRDL, but a video clip of the negotiation process by state-run China Central Television showed Biogen lowered its price to at least 34,020 yuan per injection, while a government representative counteroffered 33,000 yuan.

RELATED: Roche's low-price Evrysdi will take 'meaningful' SMA share from Biogen's Spinraza: analyst

Spinraza now boasts the distinction of being the first high-value rare disease drug included in NRDL, Biogen said on its official social media account. The Big Biotech has more reason to get Spinraza onto the NRDL this year considering that Roche broke Biogen's monopoly with a Chinese nod in June for its oral spinal muscular atrophy drug, Evrysdi. The Roche med wasn’t included in the new NRDL.

Besides Spinraza, Biogen also won coverage for multiple sclerosis drug Fampyra, for which it licensed ex-U.S. rights from Acorda Therapeutics.

Other rare disease therapies that earned their places on NRDL include Pfizer’s expected blockbuster Vyndamax (Vyndaqel) for a heart condition caused by transthyretin-mediated amyloidosis and Takeda’s Fabry’s disease treatment Replagal and hereditary angioedema therapy Firazyr, among others.

Foreign-made cancer immunotherapies miss the boat

Another closely watched negotiation centers on CD19-targeted CAR-T therapy Yescarta, marketed in China by a joint venture between Gilead Sciences’ Kite Pharma and domestic player Fosun Pharma. The drug was eligible for negotiation thanks to a June approval in third-line large B-cell lymphoma.

As the first CAR-T to enter China, Yescarta didn’t get onto the NRDL this time. The complex T-cell one-time therapy reportedly carries a sticker price of 1.2 million yuan ($188,000).

During a press conference Friday, Jie Zheng, the leader of a cost evaluation team for this round of negotiation, indicated that 300,000 yuan ($47,000) is the maximum annual cost for any drug that China’s national insurance scheme would cover, Yicai reported.

RELATED: With approval for China's 2nd CAR-T therapy, Juno, WuXi joint venture goes up against Gilead and Fosun's Yescarta

Also in the cancer immunotherapy field, once again, none of the Western-made checkpoint inhibitors made it onto the NRDL this time. Now, after a third year, without a deal, the NRDL path seems to be a dead end for foreign PD-1/L1 inhibitors such as Merck’s Keytruda, BMS’ Opdivo and AZ’s Imfinzi.

In contrast, Chinese PD-1/L1 players are busy building new indications into their offerings’ coverage scope. BeiGene, for example, added front-line non-small cell lung cancer and second-line liver cancer to tislelizumab’s reimbursed indications. Innovent Biologics and partner Eli Lilly earned Tyvyt two front-line NSCLC uses and a front-line liver cancer indication. It’s not clear how much—if any—additional discounts the companies offered to expand their drugs’ coverage.

China’s PD-1/L1 market is getting increasingly crowded with a growing list of domestic players. In August, China’s National Medical Products Administration approved two PD-1 inhibitors—Akesobio’s penpulimab and Gloria Biosciences and WuXi Biologics’ zimberelimab—both for previously treated classic Hodgkin lymphoma. Just a few days ago, envafolimab, which is jointly developed by 3D Medicines, Alphamab Oncology and Simcere Pharmaceutical, picked up an approval in China and became the world’s first subcutaneous PD-L1 antibody to be cleared anywhere.

A controversial homemade Alzheimer's drug gets a spot

Just like the U.S. has Biogen’s Aduhelm, China has its own controversial Alzheimer’s disease drug: oligomannate, or GV-971, by Chinese firm Shanghai Green Valley Pharmaceuticals.

The Chinese drug got a conditional nod in the country in 2019 based on data from a 818-patient phase 3 trial showing the drug triggered a better score on the ADAS-Cog cognitive function scale over placebo. At that time, critics pointed out the drug didn’t show a clear efficacy on other measurements of disease severity. Plus, some questioned an unusual sudden worsening of disease in the placebo group toward the end of the study.

RELATED: Biogen's Aduhelm 'likely' linked to Alzheimer's patient's death, RBC analyst says

To win coverage on NRDL, Green Valley cut GV-971’s price by 60% to 296 yuan per box, the company said Friday on its social media account. A typical patient takes about four boxes a month.

To prove its efficacy and potentially expand to markets outside China, Green Valley last year launched a global phase 3 trial. Dubbed GREEN MEMORY, the ongoing study aims to enroll more than 2,000 patients with mild to moderate Alzheimer’s disease. It will measure patients’ changes from baseline on two clinical scales, ADAS-Cog and ADCS-CGIC, as the two co-primary endpoints.

Competition heats up in several therapeutic areas

Getting onto the NRDL means wider patient reach and hence larger volume, so companies in China and abroad all consider a listing as a win, and that’s intensifying the competition.

After seeing Novartis’ blockbuster inflammation drug Cosentyx celebrate an inclusion last year, Lilly followed suit this year with rival IL-17A psoriasis med Taltz, and Johnson & Johnson did the same with IL-12/23 inhibitor Stelara.

Meanwhile, Lilly’s breast cancer drug Verzenio became the first CDK4/6 inhibitor to get onto the NRDL. Also in the cancer space, AZ’s Tagrisso is going to face more pressure, as Allist Pharmaceuticals’ third-generation EGFR inhibitor furmonertinib won national coverage.

RemeGen’s HER2-targeted antibody-drug conjugate disitamab vedotin, which was recently out-licensed to Seagen for most markets outside China, got coverage in third-line stomach cancer. By comparison, Roche’s Kadcyla didn’t enter the negotiation phase.