AstraZeneca 3 drugs approved in Japan on the same day

On August 25, AstraZeneca announced the approval of three drugs in Japan, all for new indications, including olaparib (Lynparza) approved as adjuvant therapy for patients with early-stage breast cancer carrying a BRCA mutation and at high risk of recurrence who are HER2 negative; oseltinib (Tagrisso) for the adjuvant treatment of patients with non-small cell lung cancer (NSCLC) carrying an EGFR mutation ; Ultomiris (ravulizumab), a long-acting complement C5 inhibitor, for the treatment of adults with generalized myasthenia gravis (gMG).

The PARP and BRCA1/2 genes are responsible for both DNA repair pathways, and if a mutation in the BRCA1/2 gene is present in a cancer cell and a PARP inhibitor such as olaparib is used to block the other DNA repair pathway, both DNA repair pathways are blocked and the DNA repair pathway is not affected. Both DNA repair pathways are blocked, DNA cannot be repaired in time, and apoptosis will occur in cancer cells. Normal cells, on the other hand, can still repair DNA normally and maintain stability even when they encounter PARP inhibitors because the BRCA protein is still present.

In March this year, olaparib has been approved by the FDA for the treatment of high-risk early-stage breast cancer carrying germline BRCA mutations and HER2-negative, and in August it was approved by the EU for the same indication.

This indication approval was based primarily on the Phase III OlympiA study, which showed a statistically significant and clinically meaningful improvement in invasive disease-free survival in the Lynparza group compared with the placebo group, and a 42% reduction in the risk of invasive breast cancer recurrence, new cancer, or death in the olaparib group (HR=0.58; [99.5% CI, 0.41-0.82]; p< 0.0001). The safety and tolerability of olaparib were consistent with previous trials, with the most common adverse reactions containing nausea (57%), fatigue (42%), and anemia (24%).

Ocitinib is a third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and is the only EGFR-targeted agent approved in Japan for the adjuvant treatment of postoperative early-stage lung cancer.

In the ADAURA study, oxitinib demonstrated statistically significant and clinically meaningful improvements in disease-free survival (DFS) in patients with stage II and stage IIIA NSCLC carrying EGFR mutations. The study is still ongoing and final DFS and overall survival data will be presented at the European Society of Medical Oncology (ESMO) Congress in September of this year.

Ultomiris is the first and only approved long-acting C5 complement inhibitor with immediate, complete and sustained complement inhibition and the potential to reduce patient treatment burden through once-every-8-week dosing. It works by inhibiting the C5 protein at the end of the complement cascade, which is part of the body's immune system. When the C5 protein is activated in an uncontrolled manner, the complement cascade system overreacts, causing the body to attack its own healthy cells.

In April of this year, the FDA approved Ultomiris for the treatment of adult patients with AChR antibody-positive gMG.

Results from the CHAMPION-MG study showed that MG-ADL scores in patients treated with Ultomiris showed significant improvement from baseline levels at week 26, and the study met its primary endpoint. In addition, clinical benefit from Ultomiris was consistently observed over 60 weeks in the open-label extended long-term follow-up results.