Not to be sneezed at: profit versus peril in race for allergy vaccines

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The first experimental allergy vaccine was injected into patients by two English doctors in 1911. Since then, mankind has fought two world wars, rocketed into space, developed ground-breaking cancer treatments, delved into the world of nano-science and invented the internet. Yet, on the allergy front, not much has changed.

In many respects, the sector remains extraordinarily backwards, particularly in the US, where the market is largely unregulated because of a loophole in the system.

There, vaccines against things such as pollen and dust mite are still unregistered and often administered in what can only be described as unorthodox ways: you will find doctors mashing up extracts bought from different manufacturers in their back rooms and pouring them into syringes to give to patients as “personalised” treatments to try to de-sensitise them from their allergy.

There are no standards, there is no quality control and no clinical evidence to show how effective these methods are. The situation was largely the same in Europe, until the EU started to crack down on the market in 2008 and forced companies to go through proper registration processes.

This goes some way to explain why allergy immunotherapy is such an unloved area in the pharmaceuticals market. There are fewer than 10 companies in the world focused solely on the business. A historical lack of credibility, coupled with some high-profile patient deaths from anaphylaxis as they were administered treatment, has put off doctors, businesses and investors.

Manuel Llobet, chief executive of Allergy Therapeutics
Manuel Llobet, chief executive of Allergy Therapeutics

Manuel Llobet, chief executive of Allergy Therapeutics, a publicly listed British company that develops allergy vaccines, says: “The problem with vaccines is they used to be dangerous because if you de-sensitise an allergic patient to grass and don’t know exactly the right dosage, you can trigger anaphylaxis and that is what happened in the past.

“What you find now is a mix of registered and unregistered treatments. In Europe, all vaccines now have good standards of quality and have to be made in certified manufacturing facilities. But what we don’t know yet is what kind of efficacy they are delivering, because not everyone has finished clinical trials. So there are still products in the market in both the US and Europe with no clear evidence that they work.”

Regulators on both sides of the Atlantic are, however, pushing for evidence-based medicine and tightening the rules. In a decade, Llobet reckons, all vaccines on the market will have proper data to stand them up.

This, along with a number of other factors, is leading to a step-change in a sector worth just $1bn a year, small fry in the world of pharma.

The science behind allergy vaccinations is very tricky
The science behind allergy vaccinations is very tricky

Llobet believes the industry could be worth $4bn to $5bn in five years’ time, as companies such as Allergy Therapeutics, Stallergenes and ALK-Abello, a Danish company, bring a new generation of products to market, that are safe, easy to use and effective. He thinks the allergy immunotherapy market will grow in the double digits for the next seven years.

Llobet also believes more people in the world’s emerging economies will start to suffer from allergies as their nations grow richer and more developed.

Dr Mike Mitchell, an analyst at Panmure Gordon, agrees. “I think the advent of new technological approaches is likely to generate more interest in the area,” he says. “We are seeing a real change in terms of efficacy of treatment.”

For immunologists the holy grail in allergy is to switch on and off the immune response to one specific stimulus. I think progress is being made, and while we are years away, it is not that many yearsJohn Shields, Abingworth

Modern technologies and a greater understanding of the underlying causes of allergy are spurring development of this new generation of drugs.

John Shields, an adviser at Abingworth, a private equity house that specialises in life sciences, says: “We have a better understanding of the immune system and how it is controlled.

“For immunologists the holy grail in allergy is to switch on and off the immune response to one specific stimulus. I think progress is being made, and while we are years away, it is not that many years.”

The creation of special additives that allow scientists to make vaccines with much lower levels of antigens, which are the triggers for an allergic reaction, has also helped bring down the time it takes to administer a course of treatment, making immunotherapy more palatable for patients.

A girl in a field blowing her nose
Ahhh-choo! Many people suffer from seasonal allergies

Allergy Therapeutics has developed a range of vaccines against allergens such as pollen that have gone through clinical trials and are sold in the European market which are ultra-short courses of four to six injections.

That is a far cry from existing treatments, which involve patients enduring 100 or more injections a year over three years in the hope of de-sensitising their immune systems.

The US drugs giant Merck teamed up with ALK-Abello in 2007 to launch an oral pollen vaccine in the US that had gone through clinical trials and gained regulatory approval. The trouble was, patients had to take a daily tablet for months on end, so they did not stick to the regime.

Doctors were unwilling to shift away from existing remedies, sales were low and the new treatment was a commercial disaster. In July last year, Merck returned the rights to three anti-allergy treatments to ALK-Abello partway through a clinical trial and regulatory approval process in the US, leaving ALK-Abello without a partner in the US, causing an 18pc drop in its share price.

Shields says better understanding of the allergy process means  some big pharmaceutical companies are becoming interested. Even so, it is a tricky area of science to get right. Clinical trials are based on patient reporting, and measuring allergy suffering is incredibly subjective and takes years.

Circassia, a UK pharmaceuticals company, is a good example of how easy it is to fail. It burst onto the scene with promising new treatments for cat, dust mite, ragweed and grass allergies using a new immunotherapy process called Synthetic Peptide Immuno-Regulatory Epitopes (Spires), originally developed by researchers at Imperial College.

A cat
Circassia’s treatment for cat allergy failed spectacularly

The most advanced of these immunotherapy medications was the cat allergy treatment. Clinical trials had shown hugely promising results and the company’s share price soared. This bubble burst, however, when Circassia’s last hurdle, phase three trials, did not just fail, but failed spectacularly, with an unprecedented placebo effect that had not occurred in earlier studies. The company’s shares crashed 64pc in one day.

Manufacturing is another issue: it is very labour-intensive, and therefore expensive. Dr Mitchell at Panmure Gordon explains: “What you are doing is extracting an identified allergen, modifying it and working it up into a deliverable therapeutic.

“That means the whole process of vaccine development in the allergy space is very hard to industrialise, very hard to automate. There is a lot of manual work that goes into the process.

“I watched individuals remove the venom sacks from wasps to get the venom extracted for the vaccine they were developing at Allergy Therapeutics and you need five varieties. This is cutting edge but takes a lot of manpower and is difficult to replicate.”

Despite its forecast growth, the commercial opportunity in the sector will remain small and will not, realistically, get anywhere near the much sexier areas of pharma, like immuno-oncology, Shields says.

Peanut allergies kill 300 children a year in the US and last year 200,000 emergency room visits were down to anaphylactic shock due to peanuts. Patients who have this allergy are paranoid, so there is a huge unmet need for a vaccineManuel Llobet, CEO of Allergy Therapeutics

“The market is limited. It is not going to a be a multi-billion dollar blockbuster sector. The other issue is that allergy vaccines don’t command the sorts of prices you get elsewhere in the industry, as in most cases, it’s not life-threatening.”

Still, Allergy Therapeutic’s Llobet is optimistic: “We don’t see a reason why doctors in the US and elsewhere won’t follow the European evidence-based approach,” he says.

His company is developing a vaccine for peanut allergy, which is perhaps the next big breakthrough for Allergy Therapeutics, as it is an allergy that can actually result in people dying.

“Peanut allergies kill 300 children a year in the US and last year 200,000 emergency room visits were down to anaphylactic shock due to peanuts. Patients who have this allergy are paranoid, so there is a huge unmet need for a vaccine,” he says.

Allergy Therapeutics has only just completed a proof of concept study, and a treatment will take seven to eight years to develop further. Two other companies are working on the same sort of vaccine, one in France and one in California, although neither of these are jabs, but taken orally. If Allergy Therapeutics succeeds, it would be the first injectable peanut allergy vaccine.

“Not many companies doing what we are doing. We are very happy and excited as we feel we are fulfilling a meaningful need to thousands of patients,” Llobet says.

Credit:The Telegraph-Julia Bradshaw