FDA still needs convincing that patients need HyQvia

Baxter International and Halozyme’s immune-deficiency drug HyQvia was backed almost unanimously by an FDA panel yesterday, but investors chose to muzzle their enthusiasm. It is not hard to see why.

The FDA’s briefing documents released before the hearing contained a clear critique of the product’s potential safety implications which, coming after years of regulatory heel-dragging on the technology, makes approval far from certain. The companies have to hope that their risk-mitigation plan and the expert's comments that the risks remain hypothetical are enough to convince regulators that patients, already well served in this market, need this product.

Temporary access

HyQvia is a combination of Baxter’s intravenous immunoglobulin Gammagard and Halozyme’s rHuPH20, a recombinant version of the enzyme hyaluronidase. It temporarily degrades hyaluronan, a structural component of the skin, allowing injectable biologicals such as monoclonal antibodies and other large therapeutic molecules to pass through.

In clinical testing of HyQvia almost a fifth of patients developed antibodies against rHuPH20, and the FDA has harboured concerns for some time that this could cause long-term health problems, mainly around male fertility, but also including inflammation of the bowel or brain. In staunchly sceptical briefing documents the regulator basically said that, because rHuPH20 was not therapeutically essential, it made HyQvia an unnecessarily risky proposition for patients who would be taking it throughout their lives.

The panel was far more open-minded, however, and was more focused on the fact that no adverse clinical events related to immunogenicity had been observed. It voted 15-1 in favour of HyQvia’s risk-benefit profile, and was of mixed opinion about whether the label should restrict certain patients more likely to be affected by the raised antibodies. Antibody monitoring was not advocated.

This divergence of opinion means that the FDA’s final decision, expected in the third quarter, is hard to call.

HyQvia’s main selling point would be its once-monthly subcutaneous dosing, but there are already weekly or biweekly subcutaneous formulations available and multiple IV formulations, so the regulator will not be swayed by the convenience argument.

For a product to which there are many viable and effective alternatives available, a hypothetical risk might be all the regulator needs to say no.

US access

HyQvia was first filed in 2011, and the protracted US approval process means hopes for its commercial potential have long dimmed, but a second refusal would be a big disappointment for both Halozyme and Baxter (Halozyme hurting as Baxter delay prompts wider concerns, April 17, 2012).

Baxter analysts do not split out sales forecasts from the broader Gammagard product, but UBS analysts who cover Halozyme – and recommend that investors buy the stock – reckon it could take 42% of the market for Baxter’s $2bn immunoglobulin products. An arch-rival in this space, CSL, already has a subcutaneous product on the market, called Hizentra, and HyQvia would allow Baxter to catch up.

Still, this is a particularly bullish stance; others believe that the risks to male fertility will limit HyQvia’s potential.

For Halozyme, attention has already shifted to the takeup of three approved products in Europe. Regulators there surprisingly approved HyQvia in March 2013, and have sanctioned the sale of subcutaneous versions of Roche’s Herceptin and MabThera that use Halozyme's rHuPH20.

The Roche antibodies are seen as much more important royalty streams for Halozyme, although the group will have to rely on demand from outside of the US. Owing to the launch of the pharma giant’s next-generation antibodies – Kadcyla and Gazyva – it seems a strategic decision has been taken not to launch the subcutaneous versions of the incumbents in America.

Halozyme thus needs the FDA to alter its position on HyQvia radically if it is to have a partnered product being sold in the world’s biggest drugs market. Shares in the company edged up 5.5% to $9.74 yesterday, in the wake of the advisory committee, suggesting that few investors are willing to bet on this outcome.

Halozyme sales and royalty forecasts
Sales ($m)
Product 2014e 2020e Comment Status
Hylenex 15 70 In-house sales Marketed
PEGPH20 80 Alliance revenue from Baxter option Phase II
Herceptin SC  9 75 Royalties from Roche Marketed
MabThera SC  3 32 Royalties from Roche Marketed
HyQvia (10% HyQ)  0 11 Royalties from Baxter Marketed
Halozyme/Pfizer Enhanze Project 6 Royalties from Pfizer Pre-clinical
Total 27 274

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @AmyEPVantage on Twitter

Share This Article