FDA approves ibalizumab in the US to treat multidrug HIV resistance

14 March 2018. Related: Antiretrovirals.

Simon Collins, HIV i-Base

On 6 March 2018, the US FDA approved ibalizumab as a treatment for HIV positive people with multidrug resistance who are currently on failing ART.

Ibalizumab is a monoclonal antibody that works by interfering with post-attachment steps for HIV to infect a CD4 cell. It is given by intravenous infusion every two weeks and needs to be used in combination with other active HIV drugs. Ibalizumab needs an initial loading dose of 2,000 mg followed by a maintenance dose of 800 mg every two weeks.

Approval is based on results from combined results in only 292 people during the long clinical development phase, which has been ongoing for at least a decade. The most recent TMB-301 study was in 40 highly treatment experienced participants with drug resistance to at least three classes and who were on currently failing ART. Ibalizumab was either added to current failing ART or used as monotherapy for the first week, which led to a 0.5 log reduction in viral load in 80% of participants.

Background ART was optimised to the best available combination based on resistance test results and previous treatment history.

At baseline, median viral load and CD4 cell counts were 35,350 copies/mL and 73 cells/mm³, respectively. After 24 weeks of use in combination with other drugs, viral load was reduced by a median of 1.6 log and 43% of participants achieved undetectable viral load.

The most common side effects are diarrhoea, dizziness, nausea and rash. Severe side effects include rash and immune reconstitution syndrome.

An analysis of drug susceptibility in this study was also presented at CROI 2018. [2]

For full details please see the US prescribing information. [3]

Ibalizumab was developed by TaiMed Biologics with the trade name Trogarzo. It is marketed in the US and Canada by Theratechnologies.

comment

Approval of this compound (which contributes median 1.1 log drop as monotherapy [4]) will be a life-saving drug for people with multidrug resistance. 

The US list price for ibalizumab is US $ 118,000 (WAC/Wholesale Acquisition Cost), which doesn’t include costs for providing the infusions (the product is not self-administered). Easier to use formulations are also being studied.

The company is actively engaged with the EMA to pursue the regulatory pathway for ibalizumab in the EU. [5]

Although this development took many years – with Phase 1b efficacy results first reported in 2008 – it is a considerable achievement for any compound to be the first drug approved in a new class. [6]

References

1. FDA press release. FDA approves new HIV treatment for patients who have limited treatment options. (06 March 2018).
   https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm599657.htm?
2. Weinheimer S et al. Ibalizumab susceptibility in patient HIV isolates resistant to antiretrovirals. 25th CROI, 4–7 March 2018, Boston. Poster abstract 561.
   http://www.croiconference.org/sessions/ibalizumab-susceptibility-patient-hiv-isolates-resistant-antiretrovirals (abstract and poster)
3. Ibalizumab: full prescribing information and patient leaflet.
   https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761065lbl.pdf (PDF)
4. Lalezari J et al. Primary efficacy endpoint and safety results of ibalizumab (IBA) in a phase 3 study of heavily treatment-experienced patients with multi-drugs resistant (MDR) HIV-1 infection. ID Week, 26-30 October 2016. Late breaker oral abstract LB-6.
   http://www.idweek.org
   http://www.natap.org/2016/IDSA/IDSA_06.htm
5. Personal communication, Theratechnologies.
6. Jacobson JM et al. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009; 53:450-7.
   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630626