Corporate Banner
Satellite Banner
Pharma Outsourcing
Scientific Community
Become a Member | Sign in
Home>News>This Article

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 2,800+ scientific posters on ePosters
  • More than 4,000+ 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 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

Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
Tuesday, November 10, 2015
Ebola Vaccine Trial Begins in Senegal
A clinical trial to evaluate an Ebola vaccine has begun in Dakar, Senegal, after initial research started at the Jenner Institute, Oxford University.
Thursday, July 16, 2015
Oxford Vaccine Group Begins First Trial of New Ebola Vaccine
Oxford University doctors and scientists are starting the first safety trial of an experimental preventative Ebola vaccine regimen being developed by the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen).
Wednesday, January 07, 2015
New Vaccine Generates Strong Immune Response Against Hepatitis C
A new hepatitis C vaccine has shown promising results in an early clinical trial at Oxford University, generating strong and broad immune responses against the virus causing the disease.
Friday, November 07, 2014
New Trial of Personalized Cancer Treatment Begins in Oxford
Phase I trial in Oxford will investigate a new drug, called CXD101.
Tuesday, March 18, 2014
UK Scientists to Begin Trial of Potential HIV Cure
Scientists and clinicians from five leading UK universities will begin a groundbreaking clinical trial next year to test a possible cure for HIV infection.
Tuesday, November 26, 2013
Double Dose of Tamiflu Offers No Added Benefit in Severe Flu
Early treatment with Tamiflu is beneficial for patients with uncomplicated flu infection.
Tuesday, June 04, 2013
Oxford's Role in New Meningitis Vaccine
EMA recommends Novartis' Bexero (MenB) vaccine to protect children against meningitis B.
Thursday, November 22, 2012
First Trial of a New Hepatitis C Vaccine Shows Promise
A new vaccine against the chronic liver disease hepatitis C has shown promising results in a first clinical trial in humans, Oxford University researchers report.
Thursday, January 05, 2012
TB Vaccine Enters new Clinical Trials Health
The MVA85A vaccine, developed at the University of Oxford, is to enter Phase IIb proof-of-concept clinical trials.
Thursday, April 23, 2009
Scientific News
Promising Drug Combination for Advanced Prostate Cancer
A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.
Lucentis Effective for Proliferative Diabetic Retinopathy
NIH-funded clinical trial marks first major advance in therapy in 40 years.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.
First Therapy Appearing to Reverse Decline in Parkinson’s
An FDA-approved drug for leukemia improved cognition, motor skills and non-motor function in patients with Parkinson’s disease and Lewy body dementia in a small clinical trial, say researchers at Georgetown University Medical Center (GUMC).
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Treatment for Rare Bleeding Disorder is Effective
Researchers in Manchester have demonstrated for the first time the relative safety and effectiveness of treatment, eltrombopag, in children with persistent or chronic immune thrombocytopenia (ITP), as part of an international duo of studies.
HIV Vaccine Human Trials Begin
Baltimore-based Institute has begun enrolling volunteers for initial phase 1 clinical trials.
New Therapy Reduces Symptoms of Inherited Enzyme Deficiency
A phase three clinical trial of a new enzyme replacement medication, sebelipase alfa, showed a reduction in multiple disease-related symptoms in children and adults with lysosomal acid lipase deficiency, an inherited enzyme deficiency that can result in scarring of the liver and high cholesterol.
Fixing Holes in the Heart Without Invasive Surgery
UV-light enabled catheter is a medical device which represents a major shift in how cardiac defects are repaired.
Atriva Therapeutics GmbH Develops Innovative Flu Drug
Highly effective against seasonal and pandemic influenza.
Scroll Up
Scroll Down

SELECTBIO Market Reports
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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos