Health and Prostate

The ultimate goal of treatment of benign prostatic hyperplasia and its associated comorbidities is to alleviate clinical symptoms that affect quality of life, eliminate the need for surgery, and prevent chronic and acute urinary retention. The challenge to drug developers is to create agents that have an acceptable onset of action, show a measurable level of efficacy, and induce no significant adverse events.

The pipeline of agents in development for treatment of benign prostatic hyperplasia is relatively sparse. Most of the drugs currently under investigation are in early-stage development. Because benign prostatic hyperplasia is not a life-threatening disease, safety is a primary area of product improvement for new therapies. Physicians are not willing to accept drugs with frequent or significant side effects because benign prostatic hyperplasia is not life-threatening.

Currently, the majority of pharmaceutical research for benign prostatic hyperplasia is focused on hormone therapy, as opposed to the established alpha-blocker and 5-alpha-reductase inhibitor (5-ARI) classes. The new gonadotropin modulators claim to have fewer adverse effects. If this claim is upheld, then the originator companies will most likely partner with overseas companies to comarket their new drugs in other regions. Because Japan is the only country where physicians and patients accept the use of gonadotropin modulators, uptake of some emerging therapies is expected to be higher in this region.

TABLE :Emerging Therapies in Development for Benign Prostatic Hyperplasia

In most clinical trials of agents that target benign prostatic hyperplasia, the primary end points are urinary symptom scores, average peak urinary flow rate (Qmax), and the percentage of patients who experience a clinically meaningful improvement in these two measures. These patients are also identified as “clinical responders”; they are able to achieve at least a 25% reduction in International Prostate Symptom Score (International Prostate Symptom Scores) or the American Urological Association’s Symptom Index (AUASI) and at least a 30% increase in Qmax. Some drug classes, such as the 5-ARIs and the gonadotropin modulators, because they act by reducing prostate hyperplasia, have the additional end point of reducing prostate volume.

Tadalafil, a phosphodiesterase 5 inhibitor, reduces lower urinary tract symptoms  by relaxing smooth muscle in the prostate. It does so by a different mechanism of action than alpha blockers and therefore does not involve side effects such as orthostatic hypotension and retrograde ejaculation. Tadalafil will fulfill a role as supplemental therapy for symptoms of dynamic benign prostatic hyperplasia, a niche not occupied by any other agent. Without competing drugs, tadalafil is expected to achieve strong commercial success.

The vitamin D3 analogue BXL-628 has shown efficacy similar to that of finasteride and dutasteride, and it has demonstrated an improved side-effect profile. If BXL-628 continues to show favorable, robust clinical trial results, it could replace 5-ARIs.