Health Check: Paradigm receives FDA guidance on proposed trial for dodgy knees

Paradigm Biopharmaceuticals says the FDA has endorsed key elements of its proposed phase III knee osteoarthritis trial.

Pic via Getty Images

Health Check (briefly called Alive and Kicking before we grew tired of the Simple Minds tune running through our noggins) is renowned biotech journo Tim Boreham’s NEW daily wrap covering morning movers and shakers of note in the ASX Healthcare sector, Monday through Thursday.

• Paradigm says the US drug regulator has approved the proposed dosing regimen in its proposed phase III knee osteoarthritis pivotal trial 
• Actinogen Medical launches $11.1 million raising to fund Alzheimer’s trial
• Invion reports positive data from a third-party prostate cancer trial using its phototherapy platform

Paradigm Biopharmaceuticals (ASX:PAR) Biopharmaceuticals says it has received clarity from the US Food & Drug Administration (FDA) on the design of its proposed phase III study for knee osteoarthritis.

The company hopes the trial will pave the way for approval of its drug candidate pentosan polysulfate sodium (Zilosul), which has been used as a veterinary osteo-arthritis drug and to treat a human bladder condition and deep-vein thrombosis.

“The response from the FDA a detailed set of comments that provides a pathway for progression of the company’s phase III clinical program,” Paradigm says.

Crucially, the agency has confirmed that the proposed dosing regimen of two milligrams per kilogram body weight, administered twice weekly, is the right way to go.

“In addition to feedback on the dosing regimen, the FDA provided feedback on amendments to the monitoring and mitigation plan and statistical guidance,” the company says.

Armed with this feedback, Paradigm intends to submit an updated protocol on its open Investigational New Drug (IND) application – in effect a request for permission to carry out the trial - in place with the FDA.

Paradigm expects to begin pre-screening and enrolment activities for following a mandatory 30-day review period, with preparations already underway at trial sites in the US and here.

Investors have been concerned about the progress and funding of the trial, with Paradigm shares losing two-thirds of their value over the past 12 months.

The shares this morning were 2% lower at 26 cents.

Paradigm has screeds of ‘real world’ evidence, in that hundreds of patients – notably Australian Rules footballers and Australian basketballers – have been treated under the local Therapeutic Goods Admisitraion’s special access scheme.

Last October, Paradigm also reported promising  results of a 61-patient phase II study, exploring Zilosul’s effect on knee pain and function as well as its disease-modifying characteristics via biomarker analysis of synovial fluids and MRI imaging.

While Zilosul has fast-track stats with the FDA, the agency wants a bigger trial if it is to consider approving the drug.

Paradigm had envisaged enrolment of 500 patients, but now believes it could get away with fewer and still achieve statistical significance.

Knee osteoarthritis, the most common musculoskeletal disorder that affects more than half a billion people aged over 45 globally - yet it is poorly treated.

Actinogen goes to the well for $11.1 million

Actinogen Medical (ASX:ACW) is doing the rounds for $11.1 million of funds to support and expedite its phase 2b/3 Alzheimer’s disease trial.

The raising consists of a completed $8.1 million share placement and $3 million share purchase plan, with CEO Dr Steve Gourlay subscribing for $1 million of the former.

The offer is struck at 3 cents, a 14% discount to last Friday’s close (pre trading halt). The price includes attached options on a three-for-four basis.

The moolah will be used to accelerate the full enrolment of 220 patients with biomarker-positive Alzheimer’s disease, in the 36-week placebo-controlled dubbed Xanamia.

“The funds will also allow the trial to be administered according to statistical and quality standards required to achieve pivotal status as one of two potential trials required for marketing approval in the US and globally,” the company says.

Actinogen’s drug candidate Xananem is a brain tissue cortisol synthesis inhibitor,  which inhibits production of cortisol by synthesising an enzyme called 11 beta HSD1. 

We all need a little bit of cortisol, a stress hormone, but elevated levels over a long period are thought to contribute to both Alzheimer’s and mild cognitive impairment.

Other Alzheimer’s drugs work by inhibiting amyloid proteins, which form as plaques and are thought to be a key contributor to the disease. 

The trouble is, these drugs are not overly effective.

Actinogen is running two phase II trials, with the first one assessing the  ability of Xanamem to improve cognitive dysfunction (difficulty thinking, remembering and solving problems) associated with major depression. 

On August 12 Actinogen shares tumbled as much as 67% after the company said its depression trial missed the primary endpoint of superiority over placebo, as measured by three Cogstate tests.

The trouble is, there was an “unexpectedly large improvement” in the placebo group.

But the drug fared better on the key secondary endpoint of measurement against the commonly used MontgomeryAsberg Depression Rating Scale, with the mild depression patients recording the best effects.

Anyhoo, the Alzheimer’s leg of the trial is now well funded and forging ahead, with interim results (covering the first 100 patients) expected in mid-2025 and final results in 2026.

Invion reports “promising efficacy signals” in prostate cancer trial

This one's all very apt given September is Prostate Awareness Month.

Cancer photodynamic therapy house Invion (ASX:IVX) says a recently-completed, investigator-lead  phase II trial has shown “promising efficacy” signals in prostate cancer patients.

By combining oxygen and light, photodynamic therapies are known to kill malignant cells and shut down tumors, with evidence they also stimulate the immune system. 

The results showed that 40%of  patients (four out of ten) administered with Invion’s drug candidate INV-043 sublingually showed a “positive response”, while one of them had a complete response (the tumor cleared up entirely).

Three months post-treatment, 44% (seven out of 16 patients) had negative Prostate Specific Membrane Antigen (PSMA) results as measured by positron emission tomography (having been positive previously).

“No serious adverse events were experienced and all side effects reported were mild,” the company adds.

The positive results support the potential for treating prostate cancer without the serious side effects associated with conventional remedies.

The open-label trial was carried out by the licensor of the underlying Photosoft platform, RMW Cho Group Limited and sponsored by the National Institute of Integrative Medicine.

Invion shares were steady at 0.2 cents.

 At Stockhead we tell it like it is. While Paradigm Biopharmaceuticals is a Stockhead advertiser at the time of writing, it did not sponsor this article. 

Originally published as Health Check: Paradigm receives FDA guidance on proposed trial for dodgy knees