National Institute for Health and Clinical Excellence (NICE) Releases Appraisal Consultation Document on Treatment of Pulmonary Arterial Hypertension in Adults

NEWBURY, England, March 3/PRNewswire/ -- The National Institute for Clinical Excellence (NICE) has today published
on its website the preliminary recommendations of its Appraisal Committee on
the use of epoprostenol, iloprost, bosentan, sitaxentan and sildenafil for
the treatment of pulmonary hypertension in adults.

This document is for consultation only and does not constitute the
Institute's final guidance to the National Health Service (NHS). However, if
implemented without any revisions, these proposals will significantly limit
the prescribing options for pulmonary hypertension. This will be of
particular concern to those patients in the more advanced stages of primary
pulmonary hypertension (PPH), which is a very rare, incurable and
relentlessly progressive disease. In the event that their disease progresses
to the point where oral therapy can no longer control symptoms or cannot be
tolerated, patients with PPH would have no alternative disease-specific drug
treatment available to them on the NHS.

Primary pulmonary hypertension is defined by NICE as an ultra-orphan
disease (i.e. very rare, occurring in less than 1,000 people in the UK)(i)
and before the advent of targeted therapies for PPH, when only symptomatic
treatments were available, the median survival after diagnosis was only 2.8
years.

In UK clinical practice, patients with PPH normally begin with
symptomatic treatment alone. As the disease progresses, the patient will
require disease-specific oral therapies and will eventually need a prostanoid
in order to control the advancement of the disease and maintain quality of
life. Prostanoids can be inhaled or given by intravenous infusion. The
appraisal consultation document from NICE proposes that patients are to be
denied access to prostanoid therapy and that other therapeutic choices are
limited to one first line oral therapy (sildenafil) and two alternative oral
therapies (bosentan and sitaxentan), for patients in whom sildenafil is
contraindicated or poorly tolerated.

Ventavis(R) (inhaled iloprost) has a vital role in bridging the gap
between oral therapy alone and the need for continuous IV prostanoids (e.g.
epoprostenol). It is not intended as a replacement for oral therapies.
Ventavis(R) offers advantages over IV therapy in respect to convenience and
tolerability and avoids both tachyphylaxis (large increases in dose,
therefore cost, over time) and the risks associated with the IV route of
administration.

The appraisal of Ventavis(R) by NICE omits two important considerations:

1. It does not evaluate the subgroup in which Ventavis(R) is actually
used in current UK clinical practice (i.e. in patients who have failed oral
agents and otherwise require IV epoprostenol).

2. It does not take into account either the ultra-orphan status of PPH or
the ultra-orphan drug status of Ventavis(R) (by EMEA criteria(ii)), even
though a draft discussion paper produced by NICE in 2006(i) suggests there is
a case for not applying the normal cost-effectiveness thresholds in the
appraisal of ultra-orphan diseases and specifically references iloprost in
PPH as an example.

About Pulmonary Hypertension

Pulmonary hypertension is a rare, long-term disease that affects people
of all ages and races. The cause of it is unknown and there is no cure.
However, there are several treatments which may help and information is
provided on these later.

"Pulmonary" means the disease is in the lungs. "Hypertension" is another
word for high blood pressure. In pulmonary hypertension it is harder for
blood to flow to the lungs and pressure builds up in the pulmonary artery.

Pressure is measured in millimetres of mercury or mm Hg. In healthy
people who are resting, the pressure in the pulmonary artery is about 14 mm
Hg. In pulmonary hypertension, pressure in the pulmonary artery rises above
25 mm Hg. This means the heart has to work harder and pump faster than normal
to get blood to the lungs and the rest of the body.

The heart muscle and right ventricle may get bigger than normal, to cope
with the extra work. With time the right ventricle may become weak and unable
to pump enough blood. Eventually the heart may fail completely.

Pulmonary hypertension can make the patient feel tired. Although, many
patients ignore the tiredness at first because they think it is a result of
not being particularly fit. They are likely to have difficulty in breathing
or feel like they are not getting enough air. This is called dyspnoea or
shortness of breath. The patient may experience dizzy spells and fainting,
which is called syncope. The lips and skin may appear bluer than normal
(cyanosis) and sometimes the patient will experience pain in their chest
(angina).

These are all common symptoms of pulmonary hypertension that happen
because there is not enough blood going to the lungs collecting oxygen for
the rest of the body. Also, ankles or legs may swell (oedema) because blood
is not being pumped around the body properly, so fluid collects in the legs
and ankles, especially if the patient stays on their feet for a long time.

NYHA Class

The doctor will decide how severe the disease is by using one of four
classes to describe it. These classes are from the New York Heart Association
(NYHA) and this is the NYHA classification.

What is Ventavis(R) (iloprost trometamol)?

Iloprost trometamol is a liquid containing a drug called iloprost.
Iloprost acts in the same way as a natural chemical in the body called
prostacyclin. Prostacyclin relaxes blood vessels, which helps to stop them
becoming narrow or blocked. Prostacyclin also makes blood less sticky so
clots are a little less likely to develop. Iloprost trometamol is used to
treat some, but not all cases of moderate pulmonary hypertension.

How iloprost trometamol works

By acting like prostacyclin, iloprost trometamol helps more blood get to
the lungs and collect oxygen. This tends to lower blood pressure in the
pulmonary artery and will hopefully mean less strain on the heart.

Iloprost is needed in the lungs but not in the rest of the body. For this
reason iloprost trometamol is inhaled or breathed in. This means the iloprost
trometamol liquid has to be changed into a fine spray or mist by a device
called a nebuliser. The nebuliser is then used to breathe iloprost trometamol
into the lungs.

About the NICE appraisal

NICE is appraising epoprostenol, iloprost, bosentan, sitaxentan and
sildenafil for the treatment of pulmonary arterial hypertension in adults.

The process the Institute will follow after the consultation period is
summarised below. For further details, see the 'Guide to the technology
appraisal process' (this document is available on the Institute's website;
http://www.nice.org.uk).

- The Appraisal Committee will meet again to consider the
original evidence and this appraisal consultation document in the light
of the views of the formal consultees.

- At that meeting, the Committee will also consider comments made
on the document by people who are not formal consultees in the appraisal
process.

- After considering feedback from the consultation process, the
Committee will prepare the final appraisal determination (FAD) and submit
it to the Institute.

- Subject to any appeal by consultees, the FAD may be used as the
basis for the Institute's guidance on the use of the appraised technology
in the NHS in England and Wales.

Closing date for comments: 25 March 2008

Second Appraisal Committee meeting: 3 April 2008

About Bayer Schering Pharma

Bayer Schering Pharma is a leading, worldwide speciality pharmaceutical
company. Its research and business activities are focused on the fields of
oncology, haematology & cardiology, diagnostic imaging, primary care,
specialised therapeutics and women's healthcare. With innovative products and
using new ideas, Bayer Schering Pharma aims to make a contribution to medical
progress and strives to improve the quality of patients' lives.

For more information, please visit http://www.bayerscheringpharma.co.uk

References:

(i) Appraising Orphan Drugs, National Institute for Health and Clinical
Excellence, 16 March 2006.
http://www.nice.org.uk/aboutnice/whoweare/seniormanagementteam/seniormanagementteammeetings/2005/12july2005/appraising_orphan_drugs.jsp

(ii) COMP Report to the Commission in relation to Article 10 of
Regulation 141/2000 on orphan medicinal products, European Medicines Agency
(EMEA), http://www.emea.europa.eu/pdfs/human/comp/3521805en.pdf

Press Contacts:

Sophia Cadman
Communications & PR Manager
Bayer Schering Pharma
T: +44(0)1635-563235
M: +44(0)7908-486844
sophia.cadman@bayerhealthcare.com

Steve Painter
Head of Communications
Bayer Plc
T: +44(0)1635-563524
M: +44(0)7768-467096
steve.painter.sp@bayer.co.uk

Source: Bayer Schering Pharma

Press Contacts: Sophia Cadman, Communications & PR Manager, Bayer Schering Pharma, T: +44(0)1635-563235, M: +44(0)7908-486844, sophia.cadman@bayerhealthcare.com; Steve Painter, Head of Communications, Bayer Plc, T: +44(0)1635-563524, M: +44(0)7768-467096, steve.painter.sp@bayer.co.uk

2008-03-02 20:01:54 0302189 PRNEWSWIRE