Replies to post #2416 on GTC Biotherapeutics (fka GTCB)

[Lewis R Goudy]

>rFVIIa is expensive as hell<

No kidding. Care to conjecture what they might ask for it?
Between that error bar and that of the price elasticity of
demand it seems like estimating its potential market would
be pretty tough, even for you. Would they price it purely
on revenue maximization vs the clear indications, or cheaper
to try to expand its scope of application?

[xrymd]

I spoke to a trauma surgeon a few weeks ago and he would love to use factor 7 in acute trauma but is unable due to the high cost. His words "it would bankrupt the hospital". This is a market that seems to be extremely price sensisitve and a great spot for GTCB to go after.

I am 2/3 of the way to establishing my full position. I have rolled most of my NFLD ashes into GTCB.

[DewDiligence]

Effect of rFVIIa for Treatment of ICH on Health Plan Budgets

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Select+from+History&query_key=1&WebEnv=0Y7...

>>
Manag Care Interface. 2006 Nov;19(11):39-45.

Earnshaw SR, Wilson MR, Joshi AV.

RTI Health Solutions, Research Triangle Park, North Carolina 27709, USA.

Treating patients with intracerebral hemorrhage (ICH) using recombinant activated factor VII (rFVIla) has been found to improve survival and functional outcome. To examine how the introduction of rFVIla 80 mcg/kg as a treatment for ICH affects the budget of a health plan, a decision-analysis model was developed which considered both short-term hospitalization costs and long-term management of disability.

Assuming a health plan enrollment of 1 million members and initial rFVIla uptake of 50% in appropriate patients, the annual health plan cost may be expected to increase by $64,781 ($0.005 per member per month). With a 5% increase in uptake each year, the annual health plan's cost may decrease compared with the current budget within three years.

The implications for this sample health plan's budget are modest in the first year, and a reduction in costs is expected within three years owing to improved functional outcomes of patients.
<<

[DewDiligence]

FVIIa for the Prevention and Treatment of
Bleeding in Patients Without Haemophilia

[This is a meta-analysis of 13 studies. Please see #msg-16164190 for a voluminous discussion of how FVIIa is used in practice, both on- and off-label.]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Select+from+History&query_key=1&WebEnv=0zz...

>>
Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005011.

Stanworth S, Birchall J, Doree C, Hyde C.

BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory allo-antibodies. It is also increasingly being used for off-license indications to prevent bleeding in operations where blood loss is likely to be high, and/or to stop bleeding that is proving difficult to control by other means.

OBJECTIVES: To assess the effectiveness of rFVIIa when used therapeutically to control active bleeding, or prophylactically to prevent (excessive) bleeding in patients without haemophilia.

SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, EMBASE and other specialised databases up to March 2006. We also searched reference lists of articles and contacted experts in the field.

SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any patient population with the exception of those with haemophilia. There was no restriction by outcomes examined, but this review focuses on mortality, blood loss or control of bleeding, red cell transfusion requirements, number of patients transfused and thromboembolic adverse events.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed potentially relevant studies for inclusion. Data were extracted and methodological quality was examined. Studies using rFVIIa prophylactically and those using rFVIIa therapeutically have been considered separately. Data were pooled using fixed and random effects models, but random effects models were preferred because of the variability in clinical features of the included studies.

MAIN RESULTS: Thirteen trials met the inclusion criteria; all were placebo-controlled double-blind RCTs. Six trials involving 724 participants examined the prophylactic use of rFVIIa; 379 received rFVIIa. There were no outcomes by which any observed advantage, or disadvantage, of rFVIIa over placebo could not have been observed by chance alone. There were trends in favour of rFVIIa for a number of outcomes, particularly the number of participants transfused, pooled RR 0.85 (95% CI 0.72 to 1.01) but this was balanced by a trend against rFVIIa with respect to thromboembolic adverse events, pooled RR 1.25 (95% CI 0.76 to 2.07).

Seven trials involving 1214 participants examined the therapeutic use of rFVIIa; 687 received rFVIIa. There were no outcomes where any observed advantage, or disadvantage, of rFVIIa over placebo could not have been observed by chance alone. There was a trend in favour of rFVIIa for reducing mortality, RR 0.82 (95% CI 0.64 to 1.04), although no other clear trends in favour of rFVIIa were noted for other desired outcomes. Interpretation of these results must take into account one study which could not be included in the quantitative summary but which showed results strongly in favour of rFVIIa for the treatment of intra-cerebral haemorrhage. There was a trend against rFVIIa with respect to thromboembolic adverse events; the RR 1.50 (95% CI 0.86 to 2.62).

AUTHORS' CONCLUSIONS: Although rFVIIa has a role in the management of patients with haemophilia, its effectiveness as a more general haemostatic drug, either prophylactically or therapeutically, remains uncertain. Its effectiveness as a therapeutic agent, particularly for intra-cerebral haemorrhage, looks more encouraging than prophylactic use. The use of rFVIIa outside its current licensed indications should be very limited and its wider use await the results of ongoing and possibly newly commissioned RCTs. In the interim, rFVIIa use should be restricted to clinical trials.
<<

[DewDiligence]

The Role of rFVIIa in Neurosurgery: Hope or Hype?

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&l...

>>
J Neurosurg. 2006 Dec;105(6):859-68.

Hawryluk GW, Cusimano MD.

Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Ontario, Canada.

Recombinant activated factor VII (rFVIIa) is a relatively new pharmaceutical agent developed for use in patients with hemophilia in whom inhibitors to clotting factors VIII or IX have developed. Use of this drug has become common in recent years because of its efficacy and safety in patients with coagulation disorders as well as in patients who are at high risk for thromboembolism, even when other means of establishing hemostasis have failed.

The use of rFVIIa in neurosurgery has lagged behind its use in other fields, although there is a growing body of literature on such uses. In this article the authors review the history and science of rFVIIa as well as dosing and safety information. Various uses pertinent to the neurosurgeon are reviewed, including the treatment of patients with coagulation disorders, those suffering trauma, and those with perioperative hemorrhage, intracerebral hemorrhage, or subarachnoid hemorrhage.

Based on their review of the uses of rFVIIa, the authors conclude that rFVIIa is a safe and effective agent with the potential to revolutionize the treatment of neurosurgical patients with hemorrhage. Cost is a major impediment to the widespread use of rFVIIa [something that GTC and LFB hope to change], and there is some evidence that its use in the neurosurgical population may be subject to higher risk than in other populations studied thus far. Although further study is needed to better delineate the safety and efficacy of the drug in many nonlicensed uses, it is clear that rFVIIa is an agent with tremendous promise.
<<

[DewDiligence]

rFVIIa Role as a Hemostatic Agent

http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=HistorySearch&query_key=1&WebEnv=0v1Xas2KeHdE_N...

>>
Neuroradiology. 2007 Jul 26

Hedner U, Brun NC.

University of Lund, Lund, Sweden.

Recombinant activated coagulation factor VII (rFVIIa) was developed for the treatment of patients with hemophilia who have developed inhibitors against the factor they are missing. Hemophilia is a serious bleeding disorder and patients with hemophilia develop repeated spontaneous CNS, joint and muscle bleeding. Any trauma, even mild events, may cause life-threatening bleeding, and without treatment, these patients have a life expectancy of about 16 years. Thus, hemophilia can be regarded as a model of severe bleeding, and an agent capable of inducing hemostasis in severe hemophilia independent of the hemophilia proteins (FVIII or FIX) may also be effective in patients without hemophilia who experience serious bleeds.

The availability of rFVIIa stimulated research on the role of FVII and tissue factor (TF) in the hemostatic process. As a result, a picture partly different from the one suggested by previous models has emerged. These previous models basically neglected the role of cells and cell membranes. The importance of platelets and platelet membrane phospholipids in hemostasis has been demonstrated, and the new concept of the hemostatic process, focusing on cell surfaces, has been outlined.
<<

[DewDiligence]

A Pharmacoeconomic Review of rFVIIa in
Haemophilia With Inhibitors to FVIII or FIX

[This is an important study insofar as the impetus for GTC’s FVIIa program is economic; i.e. lower-cost (transgenic) production will enable a lower product price that will expand usage. Please see #msg-16164190 for info on FVIIa usage and costs in real-world settings.]

http://tinyurl.com/ys72mb

>>
Pharmacoeconomics. 2007;25(12):1007-29.

Lyseng-Williamson KA, Plosker GL.

Wolters Kluwer Health | Adis, Auckland, New Zealand.

Recombinant factor VIIa (NovoSeven) is indicated as an intravenous haemostatic agent in haemophilia patients with inhibitors to clotting factors VIII or IX. In non-comparative trials in haemophilia patients with inhibitors, on-demand home treatment with recombinant factor VIIa was effective in controlling episodes of mild to moderate bleeding and well tolerated, with early treatment being associated with a greater rate of success and the need for fewer doses than delayed treatment.

Prophylactic treatment with rFVIIa was also effective in maintaining haemostasis in patients with this indication undergoing surgery. Relative to prior treatment with plasma-derived agents, treatment with recombinant factor VIIa was associated with improvements in health-related quality of life in a cost-utility study in haemophilia patients with inhibitors in Australia.

In well designed decision-model cost analyses conducted from a healthcare payer perspective in several countries, on-demand treatment with recombinant factor VIIa to control mild to moderate bleeding episodes in this patient population was predicted to be cost saving or cost neutral relative to on-demand treatment with intravenous activated prothrombin complex concentrate (aPCC). Although the acquisition cost of recombinant factor VIIa was greater than that of aPCC in some studies, the greater initial efficacy of recombinant factor VIIa than aPCC resulted in lower predicted total medical costs. Results were generally robust to plausible changes in key parameters.

Orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors was generally predicted to be cost saving, relative to not having surgery, over the medium to long term in modelled cost analyses from a healthcare payer perspective in the UK and US. The initial cost of surgery was high, but the difference in costs between patients undergoing or not undergoing surgery was predicted to decline over time, as savings were realised from the decrease in the number of bleeding episodes requiring treatment in patients who underwent surgery.

Conclusions: In haemophilia patients with inhibitors, recombinant factor VIIa is clinically effective in controlling mild to moderate bleeds, and in maintaining haemostasis in patients undergoing orthopaedic surgery. Available pharmacoeconomic data from several countries, despite inherent limitations, support the use of recombinant factor VIIa as a treatment option that is at least cost neutral relative to aPCC in treating mild to moderate bleeds in this patient population. In addition, orthopaedic surgery with recombinant factor VIIa to maintain haemostasis in haemophilia patients with inhibitors is generally cost saving relative to not having surgery over the medium to long term, as the acquisition costs of recombinant factor VIIa are offset by cost savings resulting from the decrease in the number of joint-related bleeds.
<<