Welcome to your weekly digest of approaching regulatory and clinical readouts. By the end of the year an interim analysis is expected from Sophiris Bio’s benign prostatic hyperplasia project PRX302. The market is dominated by oral therapies and, with generics entering shortly, injectable PRX302 needs to demonstrate its advantages clearly.
Meanwhile, FDA approval of Bristol-Myers Squibb’s Daklinza is expected by November 30. This drug is already on the market in Europe, and approval would make it the company’s first hepatitis C treatment in the US.
Sophiris Bio: PRX302
The phase III Plus-1 study enrolled 440 men aged 50 and older with lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH), a condition in which an enlarged prostate gland often results in a constricted or partially blocked urethra that can lead to pain, discomfort and other complications when urinating.
The primary endpoint is the change in International Prostate Symptom Score (assessing urinary symptoms) from baseline over 52 weeks. A three-month analysis is expected by the end of the year, with 12-month data in the second half of next year.
PRX302 is delivered directly into the prostate via localised injection. It has been engineered to be selectively activated by prostate specific antigen that is present only in prostate tissue. A single injection was given to the Plus-1 patients.
According to EvaluatePharma the only other injectable treatment in phase III is Nymox’s NX-1207. Earlier this month two US trials failed to meet their primary efficacy endpoints, and the company said the failures were due to a larger than expected placebo effect. Nymox shares plummeted 82%.
Although this may have dented confidence in PRX302, if its phase III is successful Sophiris will have the first injectable treatment available for BPH. The day after Nymox’s share crash Sophiris shares were up 25%.
Still, Sophiris has not completely evaded the placebo effect. In the phase II Triumph trial in a pre-specified efficacy-evaluable subgroup, PRX-302 demonstrated a statistically significant benefit over placebo. However, when the intent-to-treat analysis was performed the placebo-adjusted effect was smaller and not statistically significant. Sophiris will be hoping this is not repeated in phase III.
Route of admin
The BPH market is dominated by oral therapies. Glaxo’s once-daily Avodart is set to continue to lead the market by 2020 with sales of $615m, according to consensus forecasts from EvaluatePharma. Revenues were $1.3bn last year, but the patent is set to expire in 2015.
Stifel analysts expect PRX302 to gain market traction between oral therapies and currently available surgical procedures. They note that injectable therapies appear more effective than orals and less invasive than surgical options.
Leerink models a 25% probability of success, with a gross market opportunity of around $600m in 2027, so $150m adjusted for risk.
As a one-product company with only $25m in the bank, Sophiris needs its one-shot bet with PRX302 to succeed.
Bristol-Myers Squibb: Daklinza
Daklinza, known generically as daclatasvir, is an NS5A inhibitor already on the market in Europe and Japan; US approval would likely drive the majority of sales.
Approval in the US is expected, and Daklinza has breakthrough therapy designation as part of a triple combination with asunaprevir and beclabuvir (BMS-791325). With Gilead’s dominance of the one and two-drug hepatitis C space Bristol recently withdrew its US application for the dual regimen of Daklinza with asunaprevir (Harvoni OK triggers rush to three-drug hep C combos, October 13, 2014).
In Europe Daklinza is approved for use alongside Sovaldi. The combination achieved SVR12 in 99% of treatment-naïve genotype 1 patients, 100% of patients who failed treatment with telaprevir or boceprevir, 96% of those with genotype 2, and 89% of those with genotype 3.
It is Bristol’s fourth-biggest growth driver, and 2020 sales are forecast to reach $929m, after peaking at $1.1bn in 2017, according to consensus from EvaluatePharma. This makes it a valuable asset in a new therapy area for Bristol.