Commentary by Dr. Donald Greig
Osteoarthritis is a debilitating joint condition that affects hundreds of millions of people worldwide. Current treatments often provide only temporary relief or fail to address the underlying causes of the disease. However, a new drug called LEVI-04, developed by the pharmaceutical company Levicept, holds the potential to revolutionize the way we approach osteoarthritis management.
LEVI-04's unique mechanism of action sets it apart from traditional osteoarthritis therapies which involve the use of anti-inflammatories such as COX II inhibitors such as arcoxia and celebrex, proprionic acid derivatives such as ibuprofen, and voltaren. The drug candidate is based on a molecule originally discovered during research at Pfizer. This molecule is able to block a compound that supports the nerve cells responsible for transmitting pain signals to the brain. By disrupting this pain pathway, LEVI-04 can provide significant and long-lasting relief for osteoarthritis sufferers.
But LEVI-04's benefits extend beyond just pain management. The drug has also demonstrated the ability to restore protective processes within affected joints and enable the regeneration of healthy, functional tissues. This dual-action approach directly addresses the underlying degenerative nature of osteoarthritis, offering the potential to not only alleviate symptoms but also slow or potentially reverse the progression of the disease.
Importantly, LEVI-04 can be delivered through a simple once-monthly EpiPen-style injection, making it a convenient and patient-friendly treatment option. This delivery method could significantly improve treatment adherence and accessibility for the estimated 600 million people worldwide who suffer from osteoarthritis.
As the global population continues to age and the prevalence of osteoarthritis rises, the development of LEVI-04 could not have come at a more crucial time. If the drug's promising results in clinical trials are borne out, it could represent a major breakthrough in the management of this debilitating condition, offering hope to millions of patients and transforming the standard of care for osteoarthritis.
Article: Glen Keogh
An estimated 600 million patients suffer from osteoarthritis worldwide and so could benefit from a new treatment
When Simon Westbrook was made redundant by Pfizer in 2011, it would have been simpler to seek lucrative employment overseas and forget all about an “idea on a piece of paper” that he had been developing. Except he believed that that idea could lead to “one of the most important drugs ever”. “Being the maverick I was, I said to my wife, ‘Shall we just start our own biotech company?’ ” he recalled. With the support of Dominique, who also worked for the pharmaceutical giant and was made redundant at the same time, Westbrook set out alone on his creation. It was not easy. He burnt through the couple’s savings, struggled to pay the mortgage and slept in his 1972 VW orange camper van to save money while attending biotech conferences at which he was trying to attract investors. Finally in March, after a 14-year mission to develop a game-changing drug to treat osteoarthritis, Westbrook, now 54, was sitting in the courtyard of a church in the village of Colorno, Italy, when he received the news he had long been waiting for. The effectiveness of his medication had exceeded all expectations. “We saw the data [from human trials on osteoarthritic patients] and thought, ‘Oh my gosh, it’s actually worked’,” he said. “We did have a bit of a bender for a few days to celebrate. How many people can say they have actually discovered something?” Westbrook, who moved from Melbourne to study for a postdoctorate in physiology endocrinology at Cambridge University aged 26, is behind the drug known as LEVI-04, produced by his company, Levicept, which could revolutionise the treatment of osteoarthritis for the estimated 600 million sufferers worldwide.  Dominique and SimonWestbrook were made redundant afrom the pharmaceutical giant Pfizer at the sametime and decided to pool their payout to set up their own biotech company |
The drug is based on a molecule he discovered while working at Pfizer, and can be delivered via a once-a-month EpiPen-style injection, where it restores protective processes to diseased joints and enables the regeneration of affected tissues. It works by blocking a compound that supports the nerve cells involved in transmitting pain signals to the brain.
It will also be an improvement on current treatments, such as multiple anti-inflammatory pills taken daily, which can cause painful gastrointestinal side-effects and increase the risk of heart attack or stroke, or powerful opioids which can be highly addictive.
The recently completed phase-two trial of 510 patients showed sufferers reporting huge reductions in pain, increased mobility and better mental health, as they found themselves unencumbered by their illness for the first time in years.
“There was one patient who said they couldn’t wait to get back to the clinic to get their jab,” he added. “They were saying, ‘Give me more of that LEVI magic.’ We had patients who were able to take up exercise again. We had one patient who said they had taken up boxing for the first time in 15 years.
“I think it’s going to be one of the most important drugs ever. I know that sounds silly to say. But the population is getting older, it’s getting heavier. And if you can get people able to move for the first time in ten years, they’ll be able to improve their life as well.
“I think it’s going to be a ground-breaking medicine. There’s no point living to your Nineties if your life is decrepit. You’ve got to have quality of life.”
Westbrook discovered aprotein molecule that led to the new drug
More than ten million people in the UK suffer from osteoarthritis, the most common type of arthritis in the country. Symptoms include pain and stiffness, and it most commonly affects the knees, hips and the small joints of the hands. It is hoped the drug — which is not a cure but will make the condition much less painful for sufferers — could also be used to treat rheumatoid arthritis and chemotherapy-induced pain in the future. The successful phase-two trials were a welcome vindication for Westbrook’s sacrifices, after losing his job in Pfizer’s research and development facility in Sandwich, Kent, alongside 2,000 colleagues, when it was closed 13 years ago. Westbrook, who describes himself as a “drug discovery guy”, had worked in research across cardiovascular ailments, urology and obesity for 17 years at the company. He discovered the protein which would lead to LEVI-04 during his time working on pain alleviation “on my own in the corner of the lab”. “It was just an idea on a piece of paper when I was working there,” he said. “No more than that. And they [Pfizer] weren’t interested.” On leaving the company, he acquired the intellectual property [IP] rights from his former employer, best known for its accidental discovery of Viagra, and embarked on a fundraising campaign to develop the medicine. It was far from easy. During the first 18 months, he said: “We went through our savings to the point we couldn’t make mortgage payments. I remember well, my wife and I were walking down Oxford Street [in London] from one pitch to another, and she broke down saying, ‘We can’t do this any more’.” An hour later, Westbrook was told he would be receiving an initial £500,000 investment from Kevin Johnson, an entrepreneur and biotech investor, who would work alongside him for the next decade.  Westbrook describes himself as a "drug discovery guy" |
Describing anotherfundraising round, Westbrook added: “One conference was at Sandown racecourse[in Esher, Surrey] and I camped the night before in my orange VW camper vannearby, before driving to the racecourse in the morning and parking alongsidethe Mercedes-Benz and BMW cars. The camper stuck out like a sore thumb.
“Kevin [Johnson] wasat the conference and was asking who had brought the VW. When he found out itwas mine, he said he had to invest because only a true entrepreneur or a madmanwould be camping in order to raise funds.”
Johnson confirmed thestory. “I thought, ‘What crazy sod brings a camper van to a conference?’” hesaid. “It turns out it was this silly bugger who was running out of cash andtrying to eke it out as long as he could. That was the moment I decided we weregoing to back this guy.”
To complicate matters,the first time Westbrook tried to create the molecule needed for the drug atscale, it “fell apart. You need to ferment my molecule, it’s a protein. So,basically, it’s like making beer. But it didn’t work and I wasted a ton ofmoney. That was a pretty low point. But we worked out what was wrong and thenmade another batch and made the drug.”
 Westbrook used Tubeadverts to ask for clinical trial volunteers |
Since seeking initial funding for the idea, Westbrook and his team have accrued £45 million of investment from a number of firms, including Pfizer, which has a small stake taken when they negotiated the IP deal with him.
Levicept’s next problem, however, was finding human “guinea pigs” to take part in clinical trials.
As osteoarthritis sufferers tend to be older, and the trials involved patients staying in hospital for four days for tests, volunteers were few and far between.
At one point, Westbrook even placed advertisements on Tube trains asking for volunteers “interested in being paid to help with medical research” to come forward, as well as leaving leaflets in pharmacies.
He was even “on the verge of recruiting off the street”. “When I saw someone hobbling over, I wanted to say, ‘Will you do my trial?’ But that was verging on ‘mad scientist’ territory,’” he added.
Professor Philip Conaghan of Leeds University led the recent clinical trial, which was conducted at sites across Europe and Hong Kong. He called the results “truly exceptional and clinically meaningful”.
A larger clinical trial is now planned which will treat patients in the UK and US. If successful, the treatment could be available in the UK, prescribed on the NHS, within three to four years.
Westbrook added: “It’s been a long and at times tortuous journey, and I want to thank everyone who has taken part in trials, believed in this project and supported us along the way.”
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