MHRA Approves DepoDur™ For Pain Following Surgery, SkyePharma

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MHRA Approves DepoDur™ For Pain Following Surgery, SkyePharma

http://www.medicalnewstoday.com/medicalnews.php?newsid=42480

MHRA approves DepoDur™ for pain following surgery, SkyePharma

SkyePharma PLC (LSE: SKP, Nasdaq: SKYE)) announces today that the UK

Medicines and Healthcare products Regulatory Agency ( " MHRA " ) has

approved SkyePharma's DepoDur for the treatment of pain following

major surgery. Previously referred to as DepoMorphine, DepoDur

is a novel single dose sustained-release injectable formulation

of morphine.

Condella, Chief Executive of SkyePharma, said: " We are

delighted with the approval of DepoDur in the UK and are

confident that this will lead to additional approvals in other

European markets under the Mutual Recognition Process DepoDur

represents another successful outcome resulting from the major

commitment SkyePharma has made to product development, including

funding the product through Phase III trials and building and on-

going funding of a purpose-built manufacturing plant in San Diego,

USA. Our clinical trial programme for DepoDur involved over 1000

patients in four different pain models and demonstrated the great

potential of the product to improve the control of post-operative

pain.

" DepoDur was developed and is manufactured by SkyePharma Inc. the

San Diego based injectable business, which SkyePharma has announced

is in the process of being divested, " This approval, along with the

availability of EU rights for DepoDur, provides further value to

our injectable business. "

DepoDur was licensed to Zeneus for distribution in the EU.

Recently, SkyePharma bought back the rights to the product. DepoDur

is licensed to Endo Pharmaceuticals for sale in the USA.

About SkyePharma

SkyePharma PLC develops pharmaceutical products benefiting from world-

leading drug delivery technologies that provide easier-to-use and

more effective drug formulations. There are now twelve approved

products incorporating SkyePharma's technologies in the areas of

oral, injectable, inhaled and topical delivery, supported by advanced

solubilisation capabilities. For more information, visit

http://www.skyepharma.com.

About DepoDur

DepoDur is a single dose extended-release injectable formulation

of morphine sulphate. DepoDur employs SkyePharma's proprietary

DepoFoam technology and is supplied as a ready-to-use suspension.

It is given as a single epidural injection before or during surgery

and provides pain relief for up to 48 hours following surgery. There

is no need for an in-dwelling catheter for continuous infusion,

thereby overcoming a major drawback to the otherwise theoretically

desirable epidural route of administration for opioid analgesics.

DepoDur is designed for the control of pain after major surgery.

SkyePharma expects that its main use will be in control of post-

operative pain in hospitalised patients undergoing major surgical

procedures requiring general or regional anaesthesia such as major

abdominal surgery, orthopaedic surgery and caesarean section.

Currently there are an estimated 6 million such procedures every year

in the USA and 5 million in Europe.

DepoDur is supplied in a 2 ml vial containing a 10 mg/ml

suspension in sterile saline and is administered as a single dose

epidural injection at the lumbar level prior to surgery (or after

clamping of the umbilical cord during caesarean section). The

recommended dose is 10 mg for caesarean section, 10-15 mg for lower

abdominal surgery and 15 mg for major orthopaedic surgery of the

lower extremities. Some patients may benefit from a dose of 20 mg. It

should be appreciated that as with all opioids the incidence of

serious adverse respiratory events is dose-related.

Respiratory depression is the chief hazard of all opioid preparations

and occurs more frequently in elderly or debilitated patients. For

elderly patients (age >65 years), the low end of the dosing range for

DepoDur is recommended together with vigilant peri- operative

monitoring.

On 20 November 2003 SkyePharma submitted an application for DepoDur

to the UK Medicines and Healthcare products Regulatory Agency

( " MHRA " ).

Following national approval in the UK, SkyePharma now intends to seek

approval in other European Union countries under the Mutual

Recognition procedure. SkyePharma has licensed DepoDur to Endo

for North America and is now seeking a partner for the product in the

EU.

SkyePharma has completed seven clinical trials of DepoDur. The

Phase IIb and Phase III clinical development programme for DepoDur

involved four separate pain models and included more than 1000

patients. In the two Phase III trials, in hip surgery and lower

abdominal surgery, DepoDur demonstrated extended dose-related

analgesia and achieved its primary endpoint (superiority over study

comparators in terms of total demand for opioid analgesics after

surgery) with a high degree of statistical significance (p<0.0001 and

p=0.0003, respectively). DepoDur also achieved statistical

significance on several secondary endpoints.

Importantly, statistical significance was achieved for the current

pain intensity scores at rest and with activity over a 48 hour period

and for the ratings of overall pain control.

In two related Phase IIb trials, DepoDur was significantly better

than study comparators in the caesarean section study (p=0.0209) and

approached statistical significance in the knee arthroplasty study

(p=0.0902), which used a novel endpoint: time-weighted pain intensity

recall score over 48 hours. DepoDur achieved a high degree of

statistical significance in total demand for opioid analgesics after

surgery (p=0.001), a secondary endpoint in this trial but the primary

endpoint in the three other studies.

In all four of these studies the safety profile of DepoDur was

typical for an epidural opioid agent. As with all opioid

preparations, respiratory depression is the chief hazard associated

with DepoDur. The most common adverse events reported during

clinical trials were decreased oxygen saturation, hypotension,

urinary retention, vomiting, constipation, nausea, pruritus, pyrexia,

anemia, headache and dizziness.

About DepoFoam

DepoFoam is SkyePharma's proprietary extended-release injectable

delivery technology. This is fully commercialised and approved by

regulatory agencies in both the USA and Europe. DepoFoam consists

of lipid-based particles containing discrete water-filled chambers

dispersed through the lipid matrix. The particles are 10-30 microns

in diameter and are suspended in saline. The suspension resembles

skimmed milk and can be injected through a fine needle. The water-

filled chambers containing active drug account for most of the weight

of the particles. The lipids are naturally occurring substances (or

close analogues) such as phospholipids and triglycerides. The small

amount of lipid is cleared rapidly in the body as the particles

deliver their drug payload over a period that can be modified from 1

to 30 days.

About post-operative pain

After a major surgical operation, the level of pain is usually very

high for the first one to two days but the intensity of pain

gradually subsides and by the end of the second day pain can normally

be satisfactorily controlled with oral analgesics. For the immediate

post-operative period, opioid analgesics like morphine (used alone or

in combination with other non-opioid analgesics) are likely to remain

the " gold standard " for relief of severe acute pain. However the

relatively short duration of pain relief with opioids means that they

require either continuous infusion or patient-controlled analgesia

( " PCA " ) in which a pump delivers a series of doses of a short-acting

opioid analgesic in response to the patient pressing a button (under

computer control to prevent over-dosing). Both of these approaches

require the patient to have an in-dwelling epidural or intravenous

catheter. Such catheters can fall out or interfere with patient

mobility and are a potential source of infections. Epidural catheters

are also contra-indicated with concomitant use of anticoagulants

because of the risk of bleeding in the spinal column that can

potentially result in paralysis. There is a growing trend toward

routine use of anticoagulants in patients undergoing orthopaedic

surgery in order to prevent the formation of blood clots.