Trial Results Bode Well for Human Genome Sciences

The high hopes that both the market and sufferers from lupus hold for Human Genome Sciences' (HGSI) lead drug, Benlysta, showed no signs of being dashed Monday after the group and partner GlaxoSmithKline (GSK) released the hotly awaited 52-week data from their Bliss-76 trial.

While the data was not as strong as the original Bliss-52 trial, it still leaves Benlysta as the only drug in almost 50 years to show a statistical benefit in this hard to treat disorder in not one but two phase III trials. HGS’s Bliss studies have been the biggest clinical trials ever conducted in lupus and the 819 patient Bliss-76 trial showed that the drug improved symptoms at the highest 10mg/kg dose.

At the highest dose, 43% of patients with systemic lupus erythematosus (SLE), one of the more common forms of lupus, showed a significant reduction in symptoms. This compared with 40.6% on the lower dose, making the results not significantly different. In the Bliss 52 trial, however, both the higher and lower doses showed meaningful improvements. Additionally, the Bliss 76 trial failed to hit any of the secondary endpoints such as improvement in quality of life, a test that the 52 trial passed.

More to come

But weaker data or not, at the end of the day what will count is that the primary endpoint was met in both trials at the higher dose, so with these two tranches of positive data HGS and Glaxo now intend to file the drug for approval in the first half of the year. The question is now whether they will file the higher or lower dose. The higher dose is a more likely candidate given its superior performance in both trials, it would also mean that the group will be able to charge more for the drug; there had been suggestions that doctors would plump for the lower dose in an effort to keep costs down.

Given that there are no appropriate treatments other than steroids and transplant immunosuppressant drugs, both of which have major safety issues and serious drawbacks, Benlysta could realistically be on the market in the US by the second half of the year. This positions Benlysta well ahead of the competition, with the next nearest candidates in the running, including Immunomedics' (IMMU) epratuzumab and ImmunoPharma’s Lupuzor both in phase IIb trials (ACR preview – Benlysta and R788 in the spotlight, October 15, 2009).

Difference in populations

If there are any concerns about the seeming fall off in efficacy in the two trials, it could be viewed as a very good demonstration of the difficulty in treating a disease such as lupus, where symptoms not only vary greatly between patients, but can also vary from day to day in the same patient.

What might have also played a part were the differences in the trial populations between the 52 and 76 studies. The Bliss 76 trial centers were mainly based in the US and Europe, whereas Bliss 52 was conducted in Asia, South America and Eastern Europe where standards of medical care may have been lower leading to greater difference between the treatment arm and placebo.

However, this is the first part of the data, because as the name suggests the trial is due to run another 24 weeks until 76 weeks worth of data have been accumulated, even though the primary end point was 52 weeks. The continuation of the trial through an extra six months, however, could play well with the regulator who might want to see a durability of response to the drug. Running the trial for longer could also enhance the benefit produced by the drug.

By choosing a 52-week end point for this 76-week trial also means that HGS and Glaxo can get cracking with the filing of the drug, and their haste is not surprising, given the impressive sales that many believe Benlysta will achieve. According to consensus forecasts from EvaluatePharma, the drug is set to achieve sales of $1.34 billion, not bad for a product many had never expected to succeed.

The last laugh

The previously low expectations for Benlysta are reflected in the archived forecasts which were just $48 million worth of sales in 2012 in October 2008 for HGS, which is eligible to receive 50% of sales in the US. This jumped massively to $633 million this October following the Bliss 52 trial in July (Positive Benlysta data leaves Human Genome with new bulls, July 20, 2009).

What has also jumped massively is HGS' share price, which was Monday up 38% to $25.79, its highest point since February 2002. This represents a phenomenal rise since the start of the year when the shares were trading at just $2.08. If the Benlysta continues to live up to its promise and gets an easy ride at the regulator, which is not guaranteed given the drug’s novelty, then there could be more to come, making the new price targets of $30-$40 a share by some analysts seem almost believable.