RAVULIZUMAB FOR aHUS

Ravulizumab has not featured in an aHUS alliance news item heading before. Ravulizumab has been watched by the alliance from its appearance firstly as ALXN1210. It has been a promising development for a number of years now.

Ravulizumab is another “mab” – a monoclonal antibody- which is humanised -“zu”- and applies to the  immune system “li”. The “ravu” is just to distinguish it from other “lizumabs”. Who or what ravu was may be never known. It may  have been the next on a “lizumab” list, just like hurricanes get names. Or maybe even Esperanto !!?

More importantly Ravulizumab has the ingredient which is so effective for controlling the out of control Complement system which is so damaging for aHUS sufferers. It blocks C5 and stops the membrane attack complex action in its tracks.

Ravulizumab’s brand name is “Ultomiris” , as “Soliris” is for eculizumab. It is a Complement inhibitor too. In December 2018 it was given an early approval ( Alexion playing  a “rare disease priority review voucher”) by the USA’s Food and Drug Agency ,FDA, for use on adults with Paroxysmal Nocternal Heamoglobinuria, or PNH. Its marketing authorisation for PNH is still under review in Europe and Japan. (EMA since given positive opinion in April 2019, and Japan approved a licence in June 2019).

The trial of the dosing levels and safety began in December 2016 with over 240 PNH patients included. It is still an active trial but  with no further recruitment just a two year extension for participants following the initial 26 week study. More information about that trial can be read at ClinicalTrials.Gov

There are five other PNH related  Ravulizumab studies which started a few months later than the above trial, including one for children with PNH .

As with eculizumab PNH is the lead indication. What happens to those people is important to the aHUS community, particularly how it fares with health policy decisions.

For PNH trial patients ravulizumab was found “not to be inferior” to eculizumab in all the key measures compared. The difference is that only 7 or 8 treatments per annum are needed, rather than 26 eculizumab treatments. At each Ravulizumab treatment a different number of vials are infused , determined by differential weight steps above the 40kg level which had been the highest weight step. Instead of 3 vials maintenance dose infused every two weeks in the case of eculizumab, there will be 8 vials between 40 k and 60kg , 10  vials for those weighing between 60 kg and 100 kg  and 11 vials for those over 100 kg but at 8 week  intervals. Compared to eculizumab , fewer 300ml/30mg vials of Ravulizumab will be needed.

There are aHUS patients, somewhere in the world  in hospitals in Australia, Austria, Belgium, Canada,  France, Germany, Italy, Japan, Republic of Korea, Russia , Spain , Taiwan,  UK and USA (see city  locations below) , who have been  receiving Ravulizumab. Around 56 adult and adolescent ( 12 years and over) aHUS patients  and 23 children have been involved in trials since November 2016 and August 2017 respectively. Although the former trial started slightly earlier than PNH   no results have been posted at the time of writing.  The children study is still recruiting. Although underway ,no decisions have been announced yet about Ravulizumab for aHUS  by the FDA , EMA or the Japanese equivalent.  ( FDA approval  now expected by mid October 2019 see Alexion news releases here) .

It is likely going to take up to three years from now for Ravulizumab to be available for aHUS whether in countries where eculizumab  is already accessible  or hopefully in new countries too, to benefit those who need it for as long as they need it.

Just when it will be available to current , as well as for new patients ,depends on the private and public  health  insurance policy pathways in each country. The aHUS patient voice may have to play its part too.

For those benefiting from a 7 or 8 treatment a year regime  right now it is to be expected  that a more  positive message about “treatment burden” will be forthcoming. Though they will have not experienced eculizumab’s 26 treatments per annum protocol ,  or endured the extreme burden of dialysis and/or plasma therapy , they still may feel hard done by.

aHUS brings with it anxiety and self esteem issues as well as  comorbidities and treatment side effects. Issues which matter to aHUS patients and these feature in the Global aHUS patients’ research agenda. What difference will Ravulizumab make?

The price of ravulizumab is not known but Alexion has reported that the estimated cost of treatment will be 10% less than using eculizumab.

 

USA
Whittier, California, United States
Fort Wayne, Indiana, United States
Durham, North Carolina, United States, 27706
Winston-Salem, North Carolina, United States, 27103
Akron, Ohio, United States
Columbus, Ohio, United States
AUSTRALIA
Adelaide, Australia
Clayton, Australia
Geelong, Australia
Parkville, Australia
AUSTRIA
Vienna, Austria
BELGIUM
Brussels, Belgium
Bruxelles, Belgium
CANADA
London, Canada
FRANCE
Bordeaux, France
Clermont-Ferrand, France
Lille cedex, France
Montpellier, France
Nice, France
Paris, France
GERMANY
Aachen, Germany
Essen, Germany
Hanover, Germany
Muenchen, Germany
Tuebingen, Germany
ITALY
Bologna, Italy
Firenze, Italy
JAPAN
Saitama, Japan
Tokyo, Japan
REPUBLIC OF KOREA
Gyeonggi-do, Korea, Republic of
Seoul, Korea, Republic of
RUSSIA
Moscow, Russian Federation
Saint Petersburg, Russian Federation
SPAIN
Barcelona, Spain
Madrid, Spain
Valencia, Spain
TAIWAN
Taichung, Taiwan
Taipei, Taiwan
UK
Cardiff, United Kingdom
Glasgow, United Kingdom
London, United Kingdom

Children Study

USA
Aurora, Colorado,
Hollywood, Florida,
Atlanta, Georgia,
Detroit, Michigan,
Omaha, Nebraska,
Charlotte, North Carolina,
Belgium
Bruxelles,
Germany
Heidelberg,
Japan
Fuchū,
Ōbu,
Korea, Republic of
Jeju,
Seoul,
Yangsan,
Spain
Barcelona,
Esplugues De Llobregat,
Valencia,