Corporate Banner
Satellite Banner
Biomolecular Screening
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Accelerating Drug Development

Published: Tuesday, March 12, 2013
Last Updated: Tuesday, March 12, 2013
Bookmark and Share
Professor Adrian Harris is currently leading a new type of trial to accelerate multi-agent drug development.

All human clinical trials of new treatments begin with phase I, where drugs are tested in isolation to confirm their safety.

Yet most effective cancer treatments use a combination of drugs, so-called 'multi-agent ' treatments.

After phase I trials are completed, it can sometimes take up to two years before multi-agent trials are approved, never mind conducting the lengthy phase II and III trials necessary before a new drug finally reaches the market.

Professor Adrian Harris at the University of Oxford is currently leading a new type of trial which aims to significantly accelerate multi-agent drug development.

Working with the Cancer Research UK Drug Development Office (DDO) and AstraZeneca, Professor Harris' team are now running phase I trials of a new cancer drug, AZD0424.

The big difference with this trial is that researchers and patients will not need to spend years waiting for approval after phase I is complete.

Since the trial was awarded flexible approval right from the start, researchers will be able to move straight to multi-agent trials to begin testing the new drug in three different 'arms'.

Each treatment arm will pair AZD0424 with a pre-approved cancer drug from a shortlist of 5.

All drugs on the shortlist have been approved for use in the trial, and the final three partner drugs will be chosen based on experiments in mice currently being undertaken at the Edinburgh and Belfast Cancer Research UK Centres.

Refining the choice of partner drugs while phase I trials are underway in Oxford adds a further time saving to the development process, and is possible thanks to the advanced approval process.

'Although the drug may be effective on its own, we expect substantial synergy in combinations,' says Professor Harris. 'So the strength of this trial is that we are able to pair it with other drugs without having to wait for further approval between stages.'

AZD0424 works by partially blocking two proteins, Src and ABL1, which are abundant in cancerous tissue. These proteins are important for cell growth, metastasis (the spread of cancer) and blood vessel development, so blocking them helps to halt the growth of cancer cells and shuts off their blood supply.

Researchers have selected a list of drugs whose effects are expected to complement AZD0424, and the results from Edinburgh and Belfast will help decide which ones to use.

'By pairing this drug with others, we can block multiple signalling pathways to improve the overall treatment,' explains Professor Harris. 'We hope that they will have additive or synergistic effects which could reduce or inhibit tumour growth.'

When the overall effect of multiple drugs is equal to adding up their individual effects, this is known as additive.

Synergistic effects are when drugs interact such that the result is greater than the sum of their individual effects.

The partner drugs have already been shown to work individually, but this trial is about finding their combined effects in humans.

'With conventional trial structures, it's unlikely that we would be investigating this drug in a multi-agent trial,' says Professor Harris. 'The flexibility to adapt the treatments used in the multi-agent stage will allow us to match specific patient groups and cancer types to the most promising drug pairs for their circumstances. By removing the considerable cost and delay of waiting for approval between stages, we can widen the pool of viable treatments and accelerate drug development.'

Yet doesn't removing this stage compromise the safety of the trials? Not according to Professor Harris.

'The approval granted before phase I was no less rigorous than it would have been if it was given between phases,' he explains. 'All of the drugs used in the trial have been tested for safety. One of the reasons for choosing AZD0424 is that similar drugs have minimal side effects, so it's a relatively low-risk compound to begin with. We will also reduce the dosage when we begin the multi-agent phase.'

Of course, this multi-arm trial design isn't suitable for all drugs. It does take a little longer to get advanced approval in the first place, delaying the start of phase I.

The design is well suited to a drug like AZD0424, which is expected to be most effective when used with other drugs. It is also important that patients in the trial receive good clinical care at all times.

'Professor Mark Middleton leads the clinical side,' says Professor Harris. 'He's currently running the phase I clinic, and every day he provides the highest quality of care to all patients in the trial. It's important that patients are treated holistically in the clinic.'

If the trial proves successful, Professor Harris hopes that the drug could be licensed for use with partner drugs within 4-5 years. 'It's worth remembering that by using combined approaches, including radiotherapy and surgery, half of common cancers are now curable,' he adds.

'A lot of people don't realize how far we've come in recent years. While there is still much work to be done, existing treatments for many cancers are highly effective. People often forget that, and it's important to focus on the positive sometimes.'


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

First IVF Baby with New Embryo Screening Technique
The method uses the latest DNA sequencing techniques and aims to increase IVF success rates while being more affordable.
Tuesday, July 09, 2013
Key Molecule Could Reveal Many Cancers Early On
A technique for monitoring high levels of a protein found in many pre-cancerous cell types – including breast, lung and skin cancer – could be used to detect cancer early.
Wednesday, November 07, 2012
Scientific News
Promising Class of New Cancer Drugs Cause Memory Loss in Mice
New findings from The Rockefeller University suggest that the original version of BET inhibitors causes molecular changes in mouse neurons, and can lead to memory loss in mice that receive it.
Electrical Control of Cancer Cells
Research led by scientists at The University of Texas Health Science Center at Houston (UTHealth) has revealed a new electrical mechanism that can control these switches.
Signature of Microbiomes Linked to Schizophrenia
Studying microbiomes in throat may help identify causes and treatments of brain disorder.
Inflammation Linked to Colon Cancer Metastasis
A new Arizona State University research study led by Biodesign Institute executive director Raymond DuBois has identified for the first time the details of how inflammation triggers colon cancer cells to spread to other organs, or metastasize.
Structural Discoveries Could Aid in Better Drug Design
Scientists have uncovered the structural details of how some proteins interact to turn two different signals into a single integrated output.
Determining the Age of Fingerprints
Watch the imprint of a tire track in soft mud, and it will slowly blur, the ridges of the pattern gradually flowing into the valleys. Researchers have tested the theory that a similar effect could be used to give forensic scientists a way to date fingerprints.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Researchers Publish Landmark “Basket Study”
Researchers from Memorial Sloan Kettering Cancer Center (MSK) have announced results from the first published basket study, a new form of clinical trial design that explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!