Sanofi's Rare Disease Drug Laronidase Nears China Approval After 11-Month Review Under Expedited Pathway

Recently, the NMPA official website showed that Sanofi’s application for market approval of the imported therapeutic biological product laronidase concentrated solution for injection has entered the review stage and is expected to be approved for marketing in China soon, becoming another drug granted marketing authorization without clinical trials based on urgent clinical needs.

Source: NMPA

Exogenous Enzyme Replacement Drugs

Mucopolysaccharidosis storage disorders are caused by a deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs). Among these, Mucopolysaccharidosis type I (MPS I) is characterized by a deficiency of α-L-iduronidase, a lysosomal hydrolase that catalyzes the hydrolysis of terminal α-L-iduronic acid residues.

As a hydrolytic lysosomal enzyme specific for glycosaminoglycans (GAGs), laronidase is an enzyme replacement therapy for the treatment of Mucopolysaccharidosis Type I (MPS I). It is derived from in vitro cell culture and administered as an exogenous enzyme to patients with MPS I.

The fundamental mechanism of action of this therapeutic agent involves the provision of exogenous enzymes for lysosomal uptake and the enhancement of glycosaminoglycan (GAG) catabolism. It catalyzes the hydrolysis of terminal α-L-iduronic acid residues in chondroitin sulfate and heparan sulfate, thereby alleviating multi-organ dysfunction caused by polysaccharide accumulation.

Therapeutic Agents for Mucopolysaccharidosis Type I

Laronidase was initially developed by BioMarin for the treatment of patients with Mucopolysaccharidosis Type I, a company dedicated to the development of drugs for rare diseases.

In 2003, laronidase was approved by the FDA for marketing in the United States, becoming the first therapeutic agent worldwide for the rare genetic disorder mucopolysaccharidosis type I (MPS I). It is indicated for patients with Hurler and Hurler-Scheie forms of MPS I, as well as for patients with the Scheie form who exhibit moderate to severe symptoms. Conditions covered include Hurler syndrome, mucolipidosis type I, and lipochondrodystrophy.

Following Sanofi’s acquisition of BioMarin, the latter gained access to the former’s rare disease drug pipeline. To date, laronidase has received marketing authorization in multiple countries worldwide, including those in Europe and Japan.

Varieties Exempt from Clinical Trials for Market Approval Based on the List of Overseas New Drugs in Urgent Clinical Need

On November 1, 2018, the Center for Drug Evaluation (CDE) of the National Medical Products Administration issued the "Notice on Publishing the First Batch of List of Overseas New Drugs in Urgent Clinical Need," and attached the first batch of list of overseas new drugs in urgent clinical need.

The document explicitly states that drugs included in the List of Overseas New Drugs Urgently Needed for Clinical Use may submit relevant materials in accordance with the "Review and Approval Procedures for Overseas New Drugs Urgently Needed for Clinical Use," directly apply for domestic marketing approval without requiring domestic clinical trials, and the Center for Drug Evaluation (CDE) has established a dedicated pathway to expedite the review of such drugs. For drugs treating rare diseases and other medications, the CDE has set different review timelines respectively.

List of Overseas New Drugs in Urgent Clinical Need

The domestic review took 11 months.

In March 2019, the Center for Drug Evaluation of the National Medical Products Administration released the second batch of the “List of Clinically Urgent Overseas New Drugs,” publicizing a list of 30 overseas-marketed drugs in urgent clinical need, primarily rare disease treatments, which included Sanofi’s laronidase concentrate for injection.

In June 2019, Sanofi submitted a marketing application in China for laronidase concentrated solution for injection. The review process lasted 11 months, and the product is now on the verge of receiving domestic approval, becoming another drug exempt from clinical trials approved for market entry under the List of Overseas New Drugs in Urgent Clinical Need. In fact, the imported therapeutic biological product, laronidase concentrated solution for injection, submitted by Sanofi falls under the category of rare disease treatments. According to the specialized channel previously established by the Center for Drug Evaluation (CDE), the review speed could have been faster; the 11-month duration this time was likely influenced by the pandemic.

In addition, in June 2019, Vizimim, another rare disease treatment drug under BioMarin, received marketing approval from the National Medical Products Administration for the treatment of patients with mucopolysaccharidosis type IVA. This drug is the first domestically approved medication for mucopolysaccharidosis and is also one of the drugs listed in China’s first batch of the "List of Urgently Needed Overseas New Drugs for Clinical Use." It was similarly granted market authorization without requiring clinical trials.