Patent and Marketing Exclusivities 101 for Drug Developers.

Despite an ever-increasing need for newer, safer, more effective, and more affordable therapies to treat a multitude of diseases and conditions, drug development takes too long, costs too much, and is too uncertain to be undertaken without the conferment of exclusionary rights or entry barriers to motivate and sustain investment in it. These entry barriers take the form of patents that protect intellectual property and marketing exclusivity provisions that are provided by statute. This review focuses on the basic ins and outs of regulatory and patent exclusivities for which new chemical entities (NCEs), referring to never-before approved drugs with an entirely new active ingredient, are eligible and uses RRx-001, a small molecule aerospace-derived NCE in development for the treatment of cancer, radiation toxicity, and diseases of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, as a "real world" example. This is intended as a '101-type' of primer; its aim is to help developers of original pharmaceuticals navigate the maze of patents, other IP regulations, and statutory exclusivities in major markets so that they can make proper use of them.

Subset analysis of safety and efficacy in asian patients treated with RRx-001 across three clinical trials.

RRx-001, a CD47 antagonist via its inhibition of MYC and the γ-subtype of the peroxisome proliferator-activated receptor (PPAR) has been associated to date with minimal toxicity. The aim of this post-hoc analysis was to evaluate the toxicity and efficacy of RRx-001 in Asian patients since RRx-001, in the context of multiple Phase 3 studies, will be administered in China and Chinese territories as well as potentially throughout the rest of Asia. Patients received 4 mg of RRx-001 in three different antitumor clinical trials with chemotherapy and/or radiation and a retrospective subset efficacy and toxicity analysis was conducted for patients with Asian ancestry in comparison to patients with other ethnic backgrounds. The toxicity and efficacy data from these studies were similar between Asians and the rest of the treated patients. While the sample sizes are too small to draw definitive conclusions, at a dose of 4 mg, when RRx-001 is combined with chemotherapy, no apparent differences in terms of safety and efficacy are observed in cancer patients with Asian ancestry.

Just eat it: A review of CD47 and SIRP-α antagonism.

The mammalian immune system consists of two distinct arms, nonspecific innate and more specific adaptive, with the innate immune response as the first line of defense and protection, which primes and amplifies subsequent adaptive responses. On the basis of this binary immune interplay, stimulation of T cells through checkpoint inhibitors (CIs), which bypasses innate involvement, seems likely to engender suboptimal or incomplete anticancer immunity, given that the successful induction of effect or responses depends on two-way innate/adaptive coordination. Indeed, the majority of patients-70%-80%, do not respond to CIs, which is potentially problematic if access to more optimal standard therapies is withheld or delayed in favor of ineffective or only marginally effective anti-PD-1/PD-L1 treatment. Therefore, stimulation of the innate immune response in combination with CIs (or other inducers of T cell cytotoxicity) has the potential to make the immune system "whole" and thereby to enhance and broaden the anti-tumor activity of PD-1/PD-L1 inhibitors for example, in relatively nonimmunogenic or "cold" tumor types. A critical innate macrophage immune checkpoint and druggable target is the antiphagocytic and "marker of self" CD47-SIRPα pathway, which is co-opted by cancer cells to mediate escape from immune-mediated clearance and checkpoint inhibition. This review summarizes the status of key CD47 antagonists in clinical trials, including the biologics, Hu5F9-G4 (5F9), TTI-621, and ALX148, as well as the small molecule, RRx-001, now in a Phase 3 clinical trial, which has not been previously included in CD47-SIRPα reviews focused on biologics. Hu5F9-G4 (5F9), TTI-621, ALX148, and RRx-001 are chosen as compounds with potentially promising data that have advanced the farthest in clinical development.