Vasopharm seeks brain injury drug partner on positive Phase II
This article was originally published in Scrip
German firm, Vasopharm, said it is seeking a strategic partner to accelerate the further development of VAS203 for traumatic brain injury (TBI), after reporting that Phase IIa results for the drug candidate had 'exceeded expectations'.
The privately-held, Würzburg-based company said that the explorative NOSTRA trial in TBI patients met all clinical endpoints for safety "and in addition demonstrated strong evidence of clinical benefit in patients". It added that with the aid of data from the NOSTRA trial, Vasopharm is currently designing a registration study.
The firm told Scrip it was "open" in terms of the kind of deal structure sought but noted that it holds worldwide patents covering the use and structure of the drug. "We are in discussions with a number of pharmaceutical companies that are interested in VAS203," it stated.
On the market potential if the drug were to be successfully approved, Vasopharm said: "Currently we consider 500, 000 patients per year in the developed world."
With respect to Phase III development, "We still have compound on stock. The results from this trial have given us a good indication of what will be needed for the next stage of development. In the light of the unexpectedly positive outcome of the Nostra trial the company is now evaluating a range of options to take this programme forward. These include out-licensing or partnering the programme, co-development or continuing the programme in-house. We envisaged the next trial will be a Phase III study in Europe."
VAS203 is a novel allosteric NO-synthase antagonist which interrupts the inducible nitric oxide process involved in brain swelling and is the first in a new class of NOS modulators targeting cerebral vessels and cerebral tissue. It also has orphan drug designation for the treatment of moderate and severe TBI in Europe.
"It was developed in order to inhibit the inducible NO (iNOS) synthase in situ," Vasopharm explained. "The iNOS is just activated at places where the blood brain barrier opens. At these places proteins and other constituents of the blood can enter the brain tissue and thereby elicit activation of iNOS and consequently initiate severe inflammation. This is prevented because VAS203 enters the brain tissue exactly at the same time when the other 'foreigners' enter the brain parenchyma. Prerequisite for that inhibitory pharmacology is that the drug is constantly circulating in the systemic blood stream. This is why there drug is to be infused continuously of about two or more days."
NOSTRA trial details
The NOSTRA (NO-Synthase inhibition in TRAumatic brain injury) trial was a European, multicentre, placebo-controlled, double blind study with safety and tolerability as primary endpoints. The study employed in vivo microdialysis to monitor pharmacodynamic and pharmacokinetic properties of VAS203. The drug was administered in addition to standard of care treatment.
In total, 32 patients with moderate to severe traumatic brain injury were enrolled in three cohorts in six study centres in Spain, England, Austria, France and Switzerland. All study centres used continuous microdialysis to monitor cerebral energy household, NO metabolism and concentration of the drug in the brain tissue.
The company said that the trial was specifically designed to answer "crucial" questions about VAS203 and its potential to treat patients with traumatic brain injury. "We wanted to know whether the drug was safe; if it reached the site of injury in a dose dependent way; and whether it stayed there for any length of time," it stated.
Vasopharm announced that final analysis of the data showed that all clinical endpoints were achieved: the drug demonstrated good safety and tolerability and reached the brain tissues in pharmacologically relevant amounts. Furthermore, mortality was 12.5% in the placebo group versus no deaths in the drug group, it said.
"VAS203 did not have any negative effect on the cerebral perfusion pressure. The Therapy Intensity Level (TIL) – a marker evaluating concomitant therapy and intervention by the physicians as a measure for control of intracranial pressure (ICP) – demonstrated a substantial reduction in VAS203 treated patients compared to placebo. Interpretation of data on ICP – often used as a surrogate endpoint in TBI clinical trials – is impractical without reference to the intensity of therapy directed at controlling ICP."
The company added that the extended Glasgow Outcome Scale (eGOS) was used off protocol to assess the level of achieved neurological recovery six months post-injury. In comparison to the placebo group, the eGOS determined at six months post-injury, was significantly increased demonstrating a substantially improved recovery in patients receiving VAS203 (p = 0.006).
Vasopharm noted that eight patients had received placebo while another eight were treated with 15mg/kg total dose, a further eight received 20mg/kg total dose and the final eight patients were treated with 30mg/kg total dose. (The dose was adjusted by the length of the infusion time (10mg/kg/24h)).
This meant that only one patient died in the placebo arm. On why this result exceeded expectation, the company said: "The mortality of patients with such severe TBI is normally around 20% when patients are treated in well experienced trauma centres. It is therefore very surprising that none of the 24 VAS203 treated patients was lost over the entire trial period. All of them are alive and recovered significantly better than the control patients who only received standard of care. Since the trial was designed as an exploratory trial and no statistical evaluation was planned it is really exceeding our expectations, particularly because the difference in Glasgow Outcome Scale between placebo and all the patients from all dosing groups is that substantial (eGOS delta of 2)."
TBI
TBI is caused when an external force impacts the head and although it is a condition with high unmet medical need there are currently no drugs available to treat this condition. The company pointed out that around 1.7 million Americans suffer some degree of traumatic brain injury per year, resulting in 52,000 deaths, 275,000 hospitalisations, and 80,000 cases of long-term disability.
According to Vasopharm, only physical approaches can help in the treatment of TBI and the most important of these are: deep sedation (to lower brain metabolism, and thereby energy demands), lowering body temperature (also done to lower metabolism), application of osmotics to withdraw water from the brain, drainage of cerebrospinal fluid (CSF), head elevation, increased oxygenation, hyperventilation, surgery for mass lesion, control of cerebral perfusion, decompressive craniotomy, and such like.
"VAS203 can be given on top of all the standard of care activities as was the case in the NOSTRA Phase IIa trial. However, its infusion should be started not later than 18 hours after the insult," the company said.
Vasopharm
A spin-off from the University of Würzburg Medical School, Vasopharm said it is actively seeking complementary opportunities in the area of acute cardiovascular or CNS diseases preferably in late preclinical or early clinical state of development.
In addition to VAS203, Its pipeline includes VAS2870 is a NAD(P)H oxidase (NOX) modulator identified for the treatment of peripheral arterial occlusive diseases (PAOD). VAS2870 is one of several NOX modulators under evaluation at Vasopharm. Compounds of this class – which are able to increase biologically available NO in progressive and chronic diseases – have potential in the treatment of the underlying causes of several cardiovascular diseases, the company believes. However, "All our resources were focused on the development of VAS203. That's why VAS2870 and analogues are still in early stage development. A lead optimisation has still to be done," the company told Scrip.
Since it was founded in 1998, the company has secured funding of €23.0 million in four rounds of financing. Its investors are venture capital companies, silent partners as well as private investors and include Bayern Kapital Risikokapitalbeteiligungs (Landshut, Germany), EMBL Technology Fund (Heidelberg, Germany), EF Investments (Luxembourg), Future Capital (Frankfurt, Germany), HeidelbergCapital Private Equity Fund I, KfW (Frankfurt, Germany) and tbg Technologie-Beteiligungs-Gesellschaft (Bonn, Germany).