Hay fever vaccines entering new season of innovation

Analysis

Today’s positive phase II data for private company Circassia for its ragweed allergy vaccine is just the latest in string of clinical advances in field that could be set to revolutionise the multi-billion dollar hay fever and allergy market. The news from Circassia comes hot on the heels of positive phase III data from Alk Abello and Merck & Co’s SCH-039641/MK3641 ragweed vaccine, which has prompted the group to predict a filing of the drug early next year.

If successful it could potentially join three other hay fever vaccines due to come to market in 2013, including the group’s own grass pollen treatment SCH697243/MK-7243 and Allergy Therapeutic’s Pollinex Quattro Ragweed vaccine (see table below). More immediately, Allergy Therapeutics is also gearing up to have its grass vaccine Pollinex Quattro Grass approved in Europe by the end of the summer.

Currently the most widely available treatments for hay fever are coriticosteroids and anti-histamines. The drugs, however, do not treat the underlying causes of hay fever, which is estimated to effect 150m in Europe and the US. The market is also largely generic dominated by over the counter treatments that usually have the side effects of causing drowsiness.

Need for new treatments

While generally considered a minor disorder, hay fever is thought to be increasing in incidence by 5% a year in Europe and the US, it can progress to the more life-threatening allergic asthma. Developers of hay fever vaccines have argued that vaccination stops this progression and therefore should be more widely available.

Hay fever vaccines work on the principle of allergen specific de-sensitisation by damping down the over-active immune response to grass, tree and ragweed pollen. This approach also means that the effects of vaccines can be longer lasting, and some studies have shown benefits stretching out to three years post initial treatment.

There are currently several older hay fever vaccines on the market including Stallergene’s Staloral and ALK-Abelló’s Grazax, but given their age these drugs tend not to have the ability to either hit as many antigens as the newer drugs in development or generate as strong an immune response. The treatment schedule too is often less convenient, with patients needing to take both Grazax and Staloral many months before the start of the allergy season.

Next in line

But the next allergy vaccine waiting for approval, Allergy Therapeutic’s Pollinex Quattro Grass is also a relatively old technology. The drug, which is expected to find out if it has gained approval in Germany by autumn, has suffered a big setback in the US where it is still on a clinical hold.

However, there could be some regulatory progress in the US this year. The FDA has completed a review of the adjuvant used in the vaccine and has agreed to remove the hold once it has agreed clinical trial protocols with Allergy, which were submitted in November. But even if the FDA does agree them Allergy is unlike to continue clinical work in the US until it finds a development partner. The US hold has also affected the group’s phase III ragweed vaccine.

Pollinex Quattro Grass could, however, face one big stumbling block when it hits the market in Germany and if it does eventually get approval in the US: The drug is an injected medicine. The majority of treatments currently in phase III trials are transmucosal tablet, which are dissolved in the mouth and taken daily for a period of months.

Technology advances

Both of Merck’s phase III allergy vaccines, originally developed by Schering Plough, are tablets. In data shown at the American Academy of Allergy, Asthma & Immunology, the group presented data showing that its ragweed vaccine significantly reduced nasal and eye symptoms in a trial involving 565 patients. Merck is now planning to file both the ragweed and grass vaccine in early 2013; analysts are expecting a launch by the end of the year for both medicines. 

The advances in technology in the allergy vaccines space have been demonstrated by not only by the route of administration but the developments in the allergens themselves.

Although clinical progress of Biomay, Paladin Labs and Stallergenes’ STALAIR rBetV1 appears to have slowed, the tablet is the first to use a recombinant allergen as an active substance.

T-cell approach

But perhaps one of the most advanced and interesting new allergy vaccine products is Circassia’s ToleroMune Ragweed Allergy Vaccine. The product has been generated using the company’s proprietary ToleroMune platform technology, which identifies short peptide sequences called epitopes, typically 10 to 20 amino acids long, from the allergen proteins that are responsible for causing allergic reactions.

When injected, these epitopes mobilise regulatory T-cells, which downregulate components of the allergic response to the allergens. In this way, a sufferer develops tolerance of the antigen, in this case ragweed. The product also does not require adjuvants or other immune stimulators.

But while the results from the new crop of allergy vaccines are promising, and the convenience of the products increasing as they move away from injections, if hay fever vaccines are truly to come into their own and grow market share they need to not only demonstrate better efficacy than the cheap generic alternatives in the market, but also benefits in longer-term symptom control.

Allergic rhinitis vaccine late stage pipeline
Market status Allergy Product Company Routes of Admin. Treatment Regimen Trial IDs
Filed Grass Pollinex Quattro Grass Takeda/GlaxoSmithKline/
Allergy Therapeutics
Injection 4 injections administered ahead of the peak allergy season NCT00414141
Phase III Grass SCH 697243/ MK-7243 Merck & Co Transmucosal 1 dissolving tablet sublingually once daily NCT00550550,
NCT00562159,
NCT01385371
Wild-Type Grass Allergy Therapy Biomay/AllergoPharma Transmucosal Daily NCT00264459,
NCT00623701,
NCT00841256
Ragweed SCH 039641/ MK-3641 Merck & Co/ALK-Abelló Transmucosal 1 rapidly dissolving tablet, sublingually, once daily prior to and throughout the ragweed pollen season NCT00783198,
NCT00770315
Pollinex Quattro Ragweed Takeda/GlaxoSmithKline/
Allergy Therapeutics
Injection 4 injections administered ahead of the peak allergy season NCT00423787
Tree STALAIR rBetV1 Paladin Labs/Stallergenes/
Biomay
Transmucosal Daily, during approximately 5.5 months NCT00901914
Phase II Grass ToleroMune Grass Allergy Vaccine Adiga Life Sciences/Circassia Injection 1x4 administrations 4 weeks apart NCT01166061
BM32 Biomay Injection Every 4 weeks for a total of 3 injections NCT01445002,
NCT01538979
Ragweed ToleroMune Ragweed Allergy Vaccine Adiga Life Sciences/Circassia Injection 1x4 administrations 2 weeks apart NCT00878774,
NCT01448603
Tree Pollinex Quattro Tree Takeda/Allergy Therapeutics Injection Injected weekly  NCT00118625,
NCT00113750,
NCT00118612
SLITonePLUS Birch ALK-Abelló Transmucosal - NCT01191359 
AL0801rB Merck KGaA Injection - NCT00841516
AllerT birch pollen Anergis Injection Five subcutaneous injections over 2 months -

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