Sun Pharma's SMO inhibitor Sonidegib at $175m about to be granted in China

On July 13th, the status of Class 5.1 import application for "Sonidegib Phosphate Capsules" by Sun Pharmaceuticals/Jemincare (the relevant acceptance number is JXHS2100023) progressed to "under review" at the NMPA, and it is foreseen that it will be duly approved soon. The approved indications include: adult patients with locally advanced basal cell carcinoma (BCC) that recur after surgery or radiotherapy, or patients whom surgery or radiotherapy is not suitable for. 

BCC is known to be as one of the most common skin cancers, accounting for more than 80% of non-melanoma skin cancers. It is typically seen in the head and neck, particularly the nose. Locally advanced BCC refers to the spread of BCC from the initial site to nearby tissues, representing about 1-10% of all BCC cases. BCC can in general be diagnosed and treated at an early stage, while about 3% of BCC patients will relapse after 5 years of treatment. Aging of the population and increased UV exposure, etc. lead to a higher incidence of BCC by about 10% every year, and its global incidence is estimated to be 0.003%-0.55%. 

Sonidegib (Odomzo) is an oral selective Smoothened (SMO) inhibitor developed by Novartis. In July 2015, the drug was endorsed by the FDA for the treatment of locally advanced BCC adult patients who are not advised to receive surgery or radiation therapy. In December 2016, Sun Pharma grabbed global interests of the medical supplies products from Novartis at 175 million US dollars. 

Yet, Odomzo is not the only SMO inhibitor that has been approved to treat BCC. In February 2012, Roche/Genentech's SMO inhibitor Erivedge (vismodegib) was granted by the FDA for treating adult patients with symptomatic metastatic BCC or locally advanced BCC that should not be treated with surgery or radiotherapy. 

The approval for Odomzo is based on an international multi-center, randomized, double-blind Phase 2 study called BOLT. The study was carried out in adult patients with locally advanced or metastatic BCC to evaluate the efficacy and safety of 200mg and 800mg doses of Odomzo. The results reveal that: The objective response rate (ORR) of the 200mg dose group was 58%, including a complete response rate (CR) of 5%, and a partial response rate (PR) of 53%; 81% of patients with objective remission continued to have remission during a follow-up period of at least 1.9 months to 18.6 months. So far, the median duration of remission fails to be met. Moreover, no evidence has proven that the ORR data in the 800mg dose group outperforms the 200mg dose group. 

Sonidegib has been admitted to the List of the First Batch of New Drugs Urgently Needed in Clinics in China. In February 2021, Sonidegib's domestic marketing application was accepted by CDE and subsequently registered in the priority approval process. This approval will make available a new option for patients with locally advanced or metastatic BCC in China. 

It is further notable that a BCC immunotherapy was certified globally this year, namely Sanofi/Regeneron's Libtayo (cemiplimab). Libtayo, a PD-1 monoclonal antibody, was approved as a monotherapy in the United States in February 2021 for adult patients who receive a Hedgehog pathway inhibitor (HHI) treatment but the disease progresses or those with locally advanced or metastatic BCC who are intolerant to the drug. 

SMO is a 7-pass transmembrane protein and a key protein in the Hedgehog (Hh) signaling pathway. It has been reported in studies that the Hh signaling pathway is closely associated with the occurrence and development of sorts of cancers, in which the Hh signaling pathway is overactive. Besides the two approved SMO inhibitors above, another SMO inhibitor, Pfizer's Glasdegib (Daurismo), has been approved as well. Glasdegib was licensed by the FDA in November 2018. It was combined with low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) patients who are at least 75 years old or are not suitable for high-intensity chemotherapy on account of physical reasons. 

Based on incomplete statistics, an array of SMO inhibitors are currently under development, such as Taladegib, BMS-833923, LY2940680, Saridegib, TAK-441, GT1708F.