Tesamorelin (TH9507) reduces abdominal fat in patients with HIV-related lipodystrophy: 52 week results

2 December 2007. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, EACS 11 Madrid 2007.

Simon Collins, HIV i-Base

In another late breaker at the meeting, Steve Grinspoon from Massachusetts Medical School, presented 52-week results from the use of the investigational growth hormone releasing factor (GHRF) tesamorelin (2mg/day) to reduce visceral adipose tissue (VAT). [1]

At the Retrovirus conference in February this year, 26 week results were presented from 412 patients randomised to either GHRF or placebo, that showed an approximate reduction in VAT of 20% in the GHRF arm with little negative impact on limb fat. The beneficial lipids profile included reductions in TG, TC and TC:HDL ratio and an increase in HDL. [2]

In the extended study, patients who completed the initial study and had been randomised to the GHRF arm (n=211), were re-randomised to either continue using the active compound (TT, n=154) or switch to placebo (TP, n=50). Patients who completed the original study who had received placebo were switched to GHRF for the following 26 weeks (PT, n=111).

Baseline characteristics in these three group were similar and included 12% women. 90% patients had either undetectable or low level viral load <400 copies/mL. Entry criteria selected patients with high waist circumference (~ 105 +10cm), with waist:hip ratio 1.1 ­+0.1 and BMI ~ 30 + 4.5. visceral fat was increased at ~ 180 + 80 cm2.

At week 52, patients who continued on GHRF (TT) maintained the benefits seen at week 26, but did not see any additional change. Patients who received GHRF from week 26 (PT) showed a similar response by week 52 seen in the TT group. Patients who switched from GHRF to placebo (TP) lost the benefits seen at week 26 and returned close to baseline. Changes in VAT using GHRF compared to baseline were statistically significant (p < 0.001) as were changes in waist circumference (p<0.05), which approximated to reduction by 3-4 cms.

Safety data was generally good and not significantly different to placebo, and are summarised in Tables 1 and 2.

Table 1: Summary of adverse events

Table 2: Selected adverse events in >5% patients

There were no significant differences between groups or compared to baseline in glucose parameters or immune responses.

IGF levels increased in response to GHRF treatment and dropped if discontinued, explaining the increase in VAT seen in the TP group.

Approximately 50% of patients exposed to GHRF developed antibodies to tesamorelin which was not unexpected but this was not related to the treatment response.

Comment

These results are very encouraging. Central fat accumulation is not only a distressing side effect, but is an independent predictor of coronary artery disease. GHRF is more tolerable than recombinant HGH, which, apart from diet and exercise, is the only other treatment that has convincingly reduced VAT.

The disappointing aspect of these results is that GHRF appears to require maintenance treatment.

The study prompted many questions, including interest in using GHRF together with treatment switching to newer ARVs (integrase inhibitors and entry inhibitors) together with diet and exercise, cost, and to identify a suitable maintenance dose.

References:

1. Grinspoon S et al. Long-term safety and efficacy of tesamorelin (TH9507), a Growth Hormone-Releasing Factor (GRF) Analogue, in HIV-infected patients with abdominal fat accumulation. Late breaker abstract LBPS7/3.
2. See HTB March/April 2007
   http://www.i-base.info/htb/v8/htb8-3-4/Growth.html