10/18/19- FDA DECIDES

Today is significant for everyone with aHUS. Today the US Food & Drugs Administration ( FDA ) announced its decision on the use of Ravulizumab cwvz for the treatment of aHUS.
It has decided to permit Alexion Pharmaceuticals a supplemental biologics licence to market it in the USA.
Soon new onsetting patients in the USA can  be treated with Ravulizumab instead of eculizumab if their funding organisation agrees. Those already on eculizumab will be able to transition to Ravulizumab .
In the coming twelve months , if the rate of transition of treatment for PNH patients is repeated, probably all aHUS patients needing treatment in the USA will be receiving Ravulizumab.
The active ingredient of Ravulizumab  is eculizumab and it is well known that it works for aHUS patients. The key difference is that there are added modifications which make eculizumab work for longer in the blood , its “half life” ,as they say, is extended. So fewer infusions ,with longer intervals in between will result. Freeing up more time for aHUS patients away from treatment.
The cost of a vial of Ravulizumab will be less than Eculizumab. The ingredients are said to be more potent and fewer vials will be needed for treatment.
Precautions  against meningococcal infection are still a “must do” as the risk of this side of effect of blocking Complement continues to exist.
Full details of the FDA announcement can be seen here . Alexion’s press release about the decision can be read  here.
It just over 8 years since the FDA led the way in approving  eculizumab for aHUS. In that time although many aHUS patients have had their lives transformed by it; the majority of aHUS patients around the world do not have full access to the drug. Few countries have unconditional policies permitting use of the drug for patients when they need it.
It is reasonable to expect that this advancement will not make much immediate difference to access policies in other parts of the world.
Health policy making organisations in  countries of the EU, UK, Japan, Canada, and others need to make their own decisions as the FDA has today.
Alexion had said after it had submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the approval of ULTOMIRIS in TMA, including aHUS, in April 2019 that it  plans to submit similar applications to the European Medicines Agency (EMA)* and Pharmaceuticals and Medical Devices Agency (PMDA) in Japan later in 2019.
Alexion has confirmed that it has done so and that “regulatory  filings for marketing authorizations of ULTOMIRIS for the treatment of aHUS in the European Union (EU) and Japan are under review with regulators”.
The committee for medical products of human use ( CMPH) of the EMA  will first need to give a positive opinion but even if  an application is made imminently, it could be the early to middle of 2020 before the final decision could be expected.
In Europe, once the EMA has approved a licence it will be up to individual country’s health organisations to decide whether to shift their policy in favour of ravulizumab. For some countries it should be as straightforward  as it was when eculizumab was adopted for aHUS  patients. In others it will not be so, particularly in those where dosage tapering has been conducted . There Ravulizumab May struggle to be cost effective despite any proposed reduction in cost by Alexion.
How well things progress for PNH patients in Europe  may be indicative of how aHUS patients will fare.
In the U.K. an evaluation of Ravulizumab for PNH has only just begun and it could 12 to 18 months before a decision is made by NICE. That would suggest a timeline into 2021 before a transition can commence. Possibly late 2021 for aHUS at the earliest.
Such a timeline would mean that there would be only a few months until the  patent for eculizumab is due to end following the European Patent Agency decision last month to turn down Alexion’s patent extension application. It is not known whether any cheaper biosimilars would be  available by then to compete.
Drug development takes time to do and can be very expensive but it needs the participation of patients to test its efficacy. The contribution of dozens of aHUS patients around the world who have participated in Ravulizumab trials is acknowledged. They have helped and can still help others to gain the benefits from this latest technology as well.
A letter to the aHUS community from Alexion is reproduced below.
October 18, 2019 
Dear aHUS Community, 
Alexion is delighted to share the news that the U.S. Food and Drug Administration (FDA) approved a new therapy option to treat atypical Hemolytic Uremic Syndrome (aHUS) named ULTOMIRIS® (ravulizumab-cwvz). ULTOMIRIS® is a 300 mg/30mL vial injection for intravenous use for the treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement- mediated thrombotic microangiopathy (CM-TMA) for adult and pediatric (one month of age and older) patients. This is the first pediatric approval for ULTOMIRIS. CM-TMA includes a group of severe and chronic ultra-rare diseases including atypical hemolytic uremic syndrome (aHUS). For more information, please see Alexion’s press release here. (see above)
Alexion would like to celebrate the approval of ULTOMIRIS® by extending gratitude and thanks to the patients and their families who dedicated their time to participate in the clinical trial. We recognize the commitment patients make when participating in a clinical trial. Without you, bringing a new treatment to patients would not be possible. 
Alexion OneSourceTM case managers are available to answer your questions, provide educational resources, help you understand your insurance coverage and provide ongoing support throughout your continuum of care needs. To contact OneSourceTM and learn more about our services, please call (888) 765-4747. Please talk to your doctor about any questions regarding treatment decisions. 
Warm regards, 
Wendy Erler 
VP, Patient Experience 
Alexion Pharmaceuticals,
* 26 April 2019 EMA granted a positive opinion of Ravulizumab to approve a licence for the treatment of PNH and three months later in July a licence was approved. Health Canada has approved it for PNH in August 2019  as has Japan’s Ministry of Health  in June.

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