Pfizer's ($PFE) partnership with German counterpart Merck KGaA for $850 million upfront, plus as much as $2 billion in milestones, improves the prospects of PD-L1 and PD-1 checkpoint inhibitors in the oncology space, to the excitement of developers of combination therapies to the class of medicines, which feature both biological and mechanical delivery mechanisms.
For, as PD-1 and PD-L1s inhibitors come to market, demand should increase for combination therapies to increase those medications' response rate, assuming such a product is approved by the FDA.
Amgen ($AMGN) could be among the beneficiaries. It is testing its investigational talimogene laherparepvec (T-Vec) alone and in combination with Merck's ($MRK) FDA-approved PD-1 cancer therapy Keytruda (pembrolizumab). T-Vec is injected directly into the tumor, where it replicates and causes the cells to die. Once the tumor ruptures, tumor-derived antigens are released, hopefully stimulating a systemic and targeted immune response, the company explains.
"It's a competitive landscape out there in PD-1. Now you see a collaboration between two powerhouses and a willingness to work together to accelerate the development effort," Punit Dhillon, CEO of San Diego's OncoSec Medical, said in an interview with FierceMedicalDevices.
|OncoSec CEO Punit Dhillon|
San Diego's OncoSec is developing the intratumoral combination therapy ImmunoPulse to increase the response rate of anti-PD1 medications, which stands at 20% to 40% for melanoma patients and is lower for other cancers. It is delivered across the cell membrane via electroporation. "We're not using a biologic delivery, we're using electrical stimulation to briefly open the cell membrane wall and then close the cells as soon as electroporation is stopped," Dhillon said.
The delivery device is a syringe-like applicator with needles, Dhillon said.
The candidate contains a DNA plasmid encoded for production of the cytokine IL-12 in a bid to increase presence of tumor infiltrating lymphocytes (TIL) in the immune system. "If you have a high TIL (phenotype) then you're more likely to be a PD1 responder," the CEO explained.
Since the Pfizer-Merck KGaA alliance, OncoSec has announced collaborations with the Daiichi Sankyo Group, the University of Washington and the University of California, San Francisco.
The candidate is currently in Phase IIA and Dhillon says a Phase IIB trial will be announced by the end of the year, and he ultimately hopes to receive an accelerated approval pathway from the FDA.
Currently, Merck's Keytruda is the only FDA-approved PD-1 inhibitor in the U.S. Dhillon is surprised that it was approved as a second-line therapy, behind Bristol Meyer Squibb's ($BMS) anti-CTLA-4 checkpoint inhibitor Yervoy (ipilimumab), saying that the Merck product has a higher response rate than the current first-line medication.
- the release about OncoSec's partnership with Daiichi Sankyo | the University of Washington | and UC San Francisco
Editors Note: This article previously said the nonresponse rate was 20% to 40% instead of the response rate. We regret the error.