Chronic viral hepatitis: B is for billions
SummaryDespite recent advances in the treatment and management of hepatitis B, the market is still relatively immature, with several key unmet needs. Current pipeline products are expected to account for 89% of total market sales by 2015, however other developmental antivirals are also expected to contribute significantly to future market growth, potentially resulting in new treatment paradigms.
The hepatitis B market is best characterized by its overall immaturity, despite an estimated two billion persons worldwide having been exposed to the hepatitis B (HBV) virus and almost 400 million thought to be chronically infected. Historically there has been limited development of specific antiviral therapies. Indeed, the first therapy to be approved for chronic HBV (CHB) infection was interferon alfa, a non-specific immunomodulator. However, the development of the first two antivirals, GSK's Zeffix (lamivudine) and Gilead's Hepsera (adefovir dipivoxil) has led to considerable growth in the market, with these two drugs experiencing a compound annual growth rate (CAGR) of 80-90% between 1999 and 2004.
The majority of drugs undergoing clinical development belong to the nucleoside or nucleotide reverse transcriptase inhibitor (Ns/tRTI) class. Future growth is expected to be derived mainly from this class, sales of which are expected to double between 2004 and 2007. The hepatitis B market is expected to reach $1billion in sales value by 2010, and to grow at a CAGR of 8.8% to 2015.
Despite advances in therapy, unmet needs abound
HBV is a chronic disease which cannot currently be cured. As such, the major goal of therapy is the long-term suppression of viral replication, as this is associated with a reduced risk for the development of advanced liver disease including liver cirrhosis and cancer. HBV suppression is a slow process requiring long-term therapy. However, prolonged treatment with NRTIs inevitably reduces and eventually abolishes the antiviral activity requiring a switch to a different drug. Lamivudine resistance develops in approximately 24% of patients after one year and up to 67% after four years.
Until recently, the only option for patients with lamivudine resistant viral strains was therapy with adefovir, but once this option is exhausted there are no further alternatives. In addition to the requirement for drugs with activity against resistant strains, there is clearly an opportunity for drugs with delayed resistance development.
Ultimately CHB can only be fully cured through HBV eradication. This cannot be achieved with current and developmental antiviral classes and would therefore represent a major breakthrough in HBV therapy.
Baraclude and Pegasys - new kids on the block increase options for physicians
This year has seen two new drug approvals: BMS's Baraclude (entecavir) gained approval in March 2005 and Roche's Pegasys (peginterferon alfa-2a) was approved in the EU and the in early 2005, after first being approved in in late 2004. However both of these drugs offer incremental therapeutic improvements rather than revolutionary changes. In terms of efficacy and dosing regime, Pegasys is superior to the standard interferon already available for HBV therapy.
As such, physicians are expected to switch from the unmodified interferons to the pegylated version. However the target patient groups for interferon therapy are well-defined and, therefore, it is unlikely that Pegasys will capture market share from the antivirals. Nevertheless, there is scope for additional sales either as part of combination therapy with an antiviral or as successive therapy prior to or following antiviral therapy.
Similarly, Baraclude does not offer a paradigm change compared to Zeffix or Hepsera, the current antiviral standards of care, but does have superior potency and an improved resistance profile. Datamonitor's physician research found that most expect Baraclude to gradually replace Zeffix for first-line HBV therapy. Suppressive HBV therapy is necessarily a long-term process: the lower the risk for drug resistance development the longer the drug remains active, hence the higher the likelihood of achieving a durable antiviral response.
It is mainly due to its better resistance profile combined with the higher potency that Baraclude will gradually establish itself as the antiviral agent of choice for first-line HBV therapy.
Datamonitor estimates Baraclude sales to peak at just over $300 million in 2009 in the seven major markets, a year before the drug's expected patent expiry. This estimate is lower than others, which are as high as $500 million. The underlying reasons for this are that HBV incidence has been decreasing, primarily due to prophylactic vaccination, and part of the patient potential cannot be realized because not all chronically infected patients require treatment. In addition, previous Datamonitor research found that for HBV, cost is a crucial factor affecting product prescription. As such, the future uptake of Baraclude will be heavily dependent on the price attained for the drug, particularly in the cost constrained EU markets such as the and .
Baraclude and Pegasys drive early market growth
The initial value upswing following the launch of Pegasys and Baraclude is expected to be maintained by the potential launches of telbivudine and clevudine in 2007. However the HBV market is not expected to witness any further drug launches until 2009/2010 and several drugs (including Zeffix and Baraclude) will be subject to generic competition by this time. Consequently, a transient downturn in the HBV market is expected around 2011.
Datamonitor research has found that in addition to a cluster of new drug launches in 2010/11, it is expected that combination therapy will gather momentum. Regimes of NsRTI plus NtRTI, or immunomodulator, NsRTI plus NtRTI are being assessed, and have met with positive opinions from some physicians.
"I strongly believe patients should be treated with combination therapy, which all hepatologists do not believe yet because they have not seen the data," said one French key opinion leader.
Meanwhile, another based in the commented: "I think, frankly, if I had HBV now, what I would do is take Pegasys for three months and then add two highly active nucleosides; the most potent ones are probably tenofovir and entecavir."
As more companies increase their exposure to the HBV market, there will be far more opportunities for combination therapy. Investing in combination therapy, either through alliances or development of new drugs will be key to protecting product sales. However alternative strategies, such as aggressive expansion into under-served regions such as or significant increments in potency, will be vital to ensure continued growth in the HBV market for the long-term future.