Paclitaxel Injection for nandispersion (PICN)

Taxanes are the most successful drug class for solid tumors, and molecules like Paclitaxel and Docetaxel are used owing to significantly higher response rates and survival advantages in wide range of solid tumors.

Paclitaxel, an anticancer is the established standard of care for advanced cancers such as those of the breast, lung, ovary, prostate, cervix, esophagus and stomach, urinary tract and bladder, as well as head & neck.

Despite its success, Paclitaxel has some limitations. There is a very high incidence and severity of toxicities associated with its use, especially hypersensitivity reactions, neutropenia and peripheral neuropathies.There is also a high incidence of hypersensitivity reactions because of the use of excipients used to dissolve the anticancer drug.

Abraxane®the world’s first reformulated Paclitaxel product available internationally, tries to circumvent this issue of toxicity.

Abraxane® has several advantages- pre-medication with high dose corticosteroids and antihistamines is not required, a higher dose of paclitaxel can be delivered .As a result, Abraxane® commands a significant premium to generic Paclitaxel.

However, Abraxane® uses solvent processed human serum albumin. The use of albumin poses risk of immunogenicity and viral infection, specially in a patient with lowered immunity. Dosing and administration are complex and time consuming.

Abraxane® was also found to be linked to higher incidence of side effects like neuropathy compared to conventional Paclitaxel.

Our product, PICN is a novel formulation of Paclitaxel using SPARC’s proprietary nano particle platform technology. The drug achieves 30% higher concentration in tumour tissues compared to conventional paclitaxel. For PICN, the patient does not need to be prepared by giving high doses of steroids, antihistamines and antiemetics. No inline filters and special infusion sets are required. The medication also shows a linear, predictable response even at higher doses.Unlike Abraxane® quick and easy “one step” dilution and infusion preparation is offered, with a shorter infusion time. Our product offers a superior safety profile compared to Abraxane ®observed in Phase I clinical study in India.

Preclinical studies were satisfactory.

After extensive preclinical studies, Phase I clinical trials were completed in 36 patients with metastatic breast cancer, where our product showed significantly lower neutropenia and neuropathy, and a superior safety profile compared to reported data for Abraxane®.

PICN shows linear pharmacokinetics over the dose range of 135 -295 mg/ sq mt. Further, the maximum tolerated dose was 295 mg/ sq m, which was higher than the commonly used dose of Abraxane® of 260 mg/ sq mt. Which means probably a higher dose can be given in therapy. Objective response rate was observed in 10 of 25 (40%) PICN treated subjects evaluable for efficacy. There was no hypersensitivity reaction in patients treated with PICN despite the lack of pre-medication.

Phase II/ III studies, PICN has been evaluated at two doses, 260 mg/ sq mt and 295 mg/ sq mt. This is a study in180 patients with metastatic breast cancer, and the higher dose appears to be well tolerated in the patient groups being tested, with higher objective response rate. The trend of superior efficacy in Phase II trials continues to be in favor of our PICN, with greater percent reduction in tumor size from baseline.

For the US, we plan to use the 505(b)(2) route to register this product, an IND has been filed and ethics committee approval received.

We have proposed PICN as combination therapy with a platinum compound with a higher dose and a weekly dosing study with a lower dose.