A growing trend of SC injections heats up competition

to change anticancer drug formulations

Subcutaneous injectable formulations are under development for targeted anticancer agents and ADC, in addition to immunotherapy for cancer

Administration time can be significantly shortened to within 10 minutes…competitions to secure administration convenience have started

Pharmaceutical and biotech companies in Korea and worldwide focus on developing formulation modifications for anticancer agents.

 

Following 'Tecentriq (atezolizumab)' SC (subcutaneous injection obtaining marketing authorization from the European Medicines Agency (EMA) in January, the R&D of 'Opdivo (nivolumab)' and 'Rybrevant (amivantamab)' is nearing the end.

 

The industry attributes the recent booming development of SC formulations to their advantages over IV (intravenous) formulations, such as shortened administration time, improved convenience of administration, and reduced injection-related side-effects.

 

According to the industry sources on June 11th, Bristol Myers Squibb (BMS)·ONO Pharmaceutical and Janssen disclosed the research outcomes of their SC formulations products, Opdivo and Rybrevant, respectively.

 

Opdivo, an immunotherapy for cancer

Opdivo, developed by BMS and ONO Pharmaceutical, is a PD-1-targeting immunotherapy for cancer.

 

BMS conducted a clinical trial involving patients with renal cell carcinoma to change the Opdivo IV formulation to an SC formulation, and they obtained successful outcomes.

 

The Phase 3 CheckMate-67T trial enrolled 495 patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received prior therapy.

 

For safety profile, the percentage of patients with topical adverse reactions of all grades in the Opdivo SC group was 8.1%, and in the IV group, it was 2.0%.

 

Among the patients who were anti-drug antibodies (ADA)-positive, 15.2% of the patients in the SC group experienced mild topical adverse reactions of Grade 1-2, which resolved without the need of treatment.

 

SC formulation of Rybrevant, a targeted therapy for cancer, has also shown effects in a clinical trial.

 

Rybrevant, developed by Janssen, is a treatment for patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.

 

A recently disclosed Phase 3 PALOMA-3 study demonstrated the non-inferiority of SC formulation Leclaza plus Rybrevant therapy to IV formulation Leclaza plus Rybrevant therapy.

 

At a median follow-up of 7 months, SC formulation of Leclaza plus Rybrevant therapy was non-inferior to IV formulation Leclaza plus Rybrevant therapy.

 

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SC formulation of Leclaza plus Rybrevant therapy had an ORR of 30.1% compared to 32.5% in IV formulation Leclaza plus Rybrevant therapy, meeting the standard for non-inferiority.

 

For injection-related reactions (IRR), SC formulation of Leclaza plus Rybrevant therapy showed 13% IRR, which was significantly lower than 66% in IV formulation Leclaza plus Rybrevant therapy.

 

The analysis suggests that improving Rybrevant’s administration will lead to greater synergy when combined with Leclaza.

 

One of the concerns about combining oral Leclaza with IV formulation Rybrevant is that it may be less convenient due to the increased number of hospital visits.

 

Since oral formulations for targeted therapy for lung cancer, such as Tagrisso (osimertinib) and Giotrif (afatinib), have been approved, Rybrevenat’s injectable formulation poses a weakness.

 

Therefore, whether SC formulation of Rybrevant would be commercialized is attracting attention.

 

Latecomers have started developing SC formulations Latecomers to developing anticancer agents are working to change formulations to reduce the administration time.

 

Roche has succeeded in developing SC formulation of Tecentriq, an immunotherapy for cancer, and MSD is conducting a phase 3 clinical trial of SC formulation of Keytruda.

 

Alteogen, which has a SC formulation modification technology, plans to develop technology for ADC SC platform.

 

Alteogen expects the SC formulation of ADC to reduce adverse reactions.

 

The company aims to launch the SC formulation of ADC into the market by 2028.

 

The Korean pharmaceutical biotech industry is working on developing potential SC formulations of anticancer candidates.

 

GI Innovation is developing a SC formulation of GI-102, a candidate immunotherapy for cancer.

 

According to GI Innovation, the SC formulation of GI-102 has a bioavailability (BA) of up to 60% compared to an IV formulation.

 

A clinical trial for the SC formulation of GI-102 will be conducted by confirming an appropriate dose in patients with various solid cancers.

 

Once a proper dose of the SC formulation of GI-102 is determined, GI Innovation plans to conduct a clinical trial for an incremental dose in patients with solid cancer who have failed systemic therapies.

 

Additionally, several companies are working on a new formulation modification other than IV to SC.

 

Daehwa Pharmaceutical is developing an oral paclitaxel formulation, Liporaxel Sol.

 

In a phase 3 clinical trial conducted by Daehwa Pharmaceutical’s partnering company in China, Haihe Biopharma, the efficacy and safety of Liporaxel have been confirmed to be non-inferior to paclitaxel injection.