ProQR announces first results from STELLAR

Summary of Phase 1/2 Interim Analysis of QR-421a for Usher Syndrome Program

A first-in-human clinical trial of QR-421a is ongoing. The Phase 1/2 study, named Stellar, includes adults that experience vision loss due to mutation(s) in exon 13 of the USH2A gene. This Phase 1/2 clinical trial is designed to evaluate the safety and tolerability of QR-421a. Patient benefit will be assessed as well.

Three-months interim findings from Stellar, reported in March 2020, suggested QR-421a given as a single intravitreal injection was safe and well tolerated. QR-421a showed early and encouraging evidence of activity, with 25% of patients showing a benefit across multiple concordant outcome measures and was well tolerated with no serious adverse events. Two of eight participants in the treated groups responded to QR-421a treatment thus far showing benefit in multiple outcome measures.

Across both cohorts thus far, QR-421a was observed to be generally well tolerated with no serious adverse events noted. Based on these early positive findings we will continue the trial as designed at expert centers in North America and select European countries.

Read here the PDF:  Interim Findings of QR-421a Phase 1/2 Clinical Trial for Usher Syndrome and nsRP 

Read press release: ProQR Announces Positive Findings From an Interim Analysis in the Phase 1/2 trial of QR-421a for Usher Syndrome and Provides Business Update

 

If you slowly become become deaf and blind

Ronald Pennings, MD, PhD, ENT consultant and Usher syndrome specialist

Slowly become both deaf and blind. It is hard to imagine. Still, this is reality for people suffering from Usher Syndrome. Usher Syndrome, actually what type of disorder is this? And much more important: is there a treatment for stopping or slowing down the process of becoming both deaf and blind?Ronald Pennings, MD, PhD, ENT consultant and Usher syndrome specialist of the national Usher Syndrome Expert Centre in Radboudumc Nijmegen, the Netherlands, tells about this and answers the most burning questions.

‘Usher Syndrome is a hereditary disorder which affects both hearing and eyesight. In principle, the loss of hearing is always congenital. As opposed to hearing, the eyesight is normal at birth, but this will deteriorate in the course of the years.
There are three different types of Usher Syndrome: types 1, 2 and 3. People suffering from type 1 are born completely deaf and they have a poor balance. This is because the organ of balance – which is connected with the cochlea – does not work. These children will develop their first problems with eyesight at the age of eight or ten. They find it more and more difficult to see in the dark, also called night-blindness. Subsequently – as they get older – their fields of vision narrow down and as a result they will see through a kind of tunnel at a certain moment. The things they can still see will eventually become less sharp. This means that the eyesight gradually deteriorates.’

People suffering from type 2 have a congenital loss of hearing for which hearing aids can be used. These people slowly lose their hearing. The first problems with the eyesight show around puberty, a bit later than with people suffering from Usher type 1. Their eyesight will gradually deteriorate as well. Finally, we also have Usher type 3, which is very rare in the Netherlands. This type is more progressive, so here the loss of hearing as well as the loss of eyesight can go very fast.’

What is the cause of Usher Syndrome? 
‘It is a recessive hereditary disorder. Here both parents carry a fault (mutation) in one of the Usher genes without experiencing any trouble. These genes play a major role in the ears and eyes of people, making sure that we can hear and see well. We have two ‘copies’ of each gene. If one copy has a fault, you are carrier but you will not suffer from Usher, because you also have a normal copy. At the moment that both parents pass on their faulty copies of the gene to their child, the child will suffer from Usher Syndrome. In this case the child does not have a normal copy of this gene left.

The copy in which the fault is present will prevent the gene from properly producing its protein. This protein is important for both hearing and eyesight. If you have another good copy, you will have a normal protein on that side. At the moment that both copies are faulty, you will no longer produce a normal protein. When the proteins are not working well, there will be loss of hearing and deterioration of eyesight.’

How big is the change of developing Usher Syndrome?
‘The syndrome is rare, which makes the chance of a child suffering from Usher very small. A child with normal hearing has virtually no chance of Usher Syndrome. In case of congenital hardness of hearing this chance will be larger, about three to six percent. For each form of congenital loss of hearing it is advised to conduct a genetic test for the cause of this. This test can confirm Usher Syndrome, even if there are no problems with seeing yet. When both parents are carriers of a mutation in the same Usher gene, they have 25 percent chance of getting a child with the syndrome.”

How often does this occur?
‘We do not have any exact numbers, but we think that about 800 people suffer from Usher Syndrome in the Netherlands. So this really is a rare syndrome.’

How do people suffering from Usher Syndrome cope with the knowledge that they will slowly become both deaf and blind?
‘In very different ways and with ups and downs. You sometimes see people being seriously confronted with their impairments, as everything costs more energy. On the other hand, there are also periods in which they really try to make things work and make the most of their lives.
There is a lot of power behind this and that is the nice thing about this group of people. That they are still very active despite their impairments. This shows, for instance, in a foundation that have been set up by patients and their relatives, such as Stichting Ushersyndroom. This are a very active foundation that try to improve the lives of people suffering from Usher.’

Is there a treatment?
‘The deaf children suffering from type 1 can be given a cochlear implant. This is an implantable hearing aid with which we place an implant with an electrode in the cochlea. The implant converts sounds into an electric pulse, which then is passed on to the cochlea. After a rehabilitation process, people will be able to hear with this. This makes sure that these children instead of growing up as deaf children grow up as children with a hearing impairment, but they can go to a regular school. To type 2 applies that both children and adults can be rehabilitated with a hearing aid. Sometimes older people suffering from type 2 need a cochlear implant because of the progress of the loss of hearing.

So there is a lot we can do to improve the hearing with the current state of affairs. With respect to eyesight, however, there still really is a problem. Genetic therapies are being developed at this moment, but for this we need to know what is genetically going on. It is important to investigate this and to make a diagnosis based on this. By now, the first steps towards developing gene therapies for the three types have been taken. We are also working on a future treatment for type 2 in our laboratory. However, it will still take many years for a treatment to become available. For the time being, the objective of this study is to slow down or even stop the deterioration of the eyesight in particular.

At this moment, we do not expect that we will be able to give someone who has become blind his or her eyesight again. However, if we indeed manage to slow down or even stop the deterioration process, we have really achieved a lot for the younger patients. This is all still in the future. The first clinical trials have started and we have to wait for the results of these and whether they will lead to medicines for this group of people.’

What can people do themselves?
‘There are indications that exposure to intense (sun)light – also on cloudy days on which the light is intense – it is useful to wear a hat and sunglasses. This could partly protect against increasing damage of the retina. Another important thing is: people suffering from Usher should be careful with their ears, for instance at festivals, clubs or loud music. In these situations they’d better take off their hearing aids or not stand very close to the loudspeakers, although most people suffering from Usher Syndrome will sufficiently take this into account by themselves.’

Dr. Ronald Pennings is ENT specialist and otologist at Radboudumc in Nijmegen, the Netherlands. The Radboud University Medical Centre is an academic hospital and cooperates with the Radboud University of Nijmegen.

Source: Gezondheidsnet [Health net] and NU.nl