The shock news! Roche ends development of olesoxime

It was announced today that Roche has taken the difficult decision of ending the development of neuro-protective compound Olesoxime.

In 2016 Roche started the OLEOS study, an open label extension study evaluating the long term safety and effectiveness of olesoxime. Many discussions with Health Authorities (FDA and EMA) and SMA experts were had and the company worked hard to improve the dose and formulation of olesoxime and to design the best Phase 3 study possible to be able to show the efficacy of olesoxime.

Furthermore, they regularly analysed the data from this study. Whilst the data at 12 months of treatment with olesoxime were initially encouraging, the most recent analysis at 18 months, which was presented at the American Academy of Neurology in April 2018, actually showed a worsening in motor function.

Unfortunately, despite all of their efforts and a strong desire to deliver olesoxime as a medicine to people with SMA, Roche has concluded that this is not going to be possible. Based on all of the available evidence and the continued difficulties described above, the company has decided to stop further development of olesoxime.

Many of you will be very disappointed by this news, as we are too. Their immediate priority now is to ensure that those still taking part in the ongoing OLEOS study understand what this decision means for them and that they are provided with appropriate treatment options. Roche is working closely with study sites and investigators to help identify options for those still taking part in the OLEOS study and will share more details about this in the coming weeks. The OLEOS study will be kept open until all ongoing participants have an alternative treatment option confirmed.

text from: http://www.sma-europe.eu/news/roche-ends-development-of-olesoxime/

Phase 2 clinical trial Roche in Europe

A Phase 2 clinical trial evaluating the efficacy and safety of RG7916 in children and adults with type 2 or 3 spinal muscular atrophy (SMA) has advanced into a second and possibly pivotal phase. The study is part of a development program jointly led by PTC Therapeutics, Roche and the SMA Foundation.

The SUNFISH trial (NCT02908685) consists of two parts: an exploratory dose-finding initial part that ran for 12 weeks and a confirmatory part that will run for 24 months. This second part is randomized, double-blinded and placebo-controlled. Approximately 168 type 2 and 3 SMA patients, ages 2 to 25, are expected to enroll at sites in four European countries. When SUNFISH concludes in about two years, patients may continue in an open-label extension of this study.

An interim analysis from its first part demonstrated an exposure-dependent increase in the survival motor neuron (SMN) protein, which is deficient in these patients. RG7916 continues to be well-tolerated at all doses and no drug-related safety findings led to any patients withdrawing from part one.

RG7916 is an oral survival motor neuron 2 (SMN2) splicing modifier. Because SMA is caused by a defect in the SMN1 gene, the SMN2 gene has been explored as a potential replacement to guarantee the production of the SMN protein.

Messenger RNA (mRNA) is the molecule that guides protein formation. Pre-mRNA is a less developed version of mRNA. In order for pre-mRNA to become mRNA, the genetic material in pre-mRNA must be edited through a process called “splicing,” where some sections are removed.

To say that RG7916 is a splicing modifier means that it directly targets the underlying molecular deficiency of SMA by modulating SMN2 splicing to increase expression of full-length SMN2 mRNA from the SMN2 gene.

“We are excited to move RG7916 into the pivotal part of the SUNFISH trial,” Stuart W. Peltz, PhD, chief executive officer of PTC Therapeutics, said in a press release. “RG7916 resulted in a substantial increase in SMN2 protein production in SMA patients. We believe that a major advantage of RG7916 is that it is an oral drug that distributes throughout the body. This is important because the SMN protein is critical both in the CNS and peripheral tissues.”

RG7916 is also being investigated in babies with type 1 or infant-onset SMA in a Phase 2 trial called FIREFISH (NCT02913482). This study, running at sites in the U.S. and Europe, is currently recruiting infants ages 1 to 7 months old.

PTC Therapeutics and the SMA Foundation initially began working on this potential therapy in 2006, and Roche began to participate in 2011, when it acquired an exclusive worldwide license to this splicing program. The U.S. Food and Drug Administration (FDA) designated RG7916 an orphan drug for the treatment of SMA in January 2017.

Initiation of the second part of SUNFISH triggered a $20 million milestone payment to PTC from Roche.

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Trial of SMA Therapy RG7800 on Hold, but Roche, Partners Developing Another Compound September 20, 2016 Charles Mooreby Charles Moore In News.

International pharmaceutical company Roche, with its SMA drug development collaboration partners PTC Therapeutics and the SMA Foundation, said a clinical study called Moonfish (NCT02240355) that was investigating a compound and investigational medicine known as RG7800 for people with spinal muscular atrophy (SMA) was placed on clinical hold in April 2015 after an unexpected eye finding in an animal study

Roche, PTC, and the SMA Foundation announced the hold in an update on the clinical development program of SMN2 splicing modifier drug development program for treating SMA.

However, the partners are developing another SMN2 splicing modifier compound called RG7916 that is still in early clinical stages.

Roche said that concentrations of RG7800 being tested in the animal study were higher than those received by any of the Moonfish study’s human participants, and the company says it can can confirm that no safety issues have been identified in any person who received RG7800 through their participation in the Moonfish study.

RG7800 is an investigational oral drug for the treatment of SMA, a genetic disorder caused by the mutation or deletion of the survival of motor neuron gene 1 (SMN1).

curesmalogoRoche and its partners believe RG7800 may have potential to target SMA’s underlying cause by increasing SMN protein levels in the nervous system, muscles, and other tissues through modifying SMN2 gene splicing to stimulate greater production of full-length SMN mRNA.

The SMN2 splicing modifier drug development program was originally launched by PTC Therapeutics in partnership with the SMA Foundation. The program was designed to utilize PTC’s Alternative Splicing technology platform to identify and develop new small-molecule therapeutics in treating and prevention of SMA.

In November 2011, Roche gained an exclusive license to the program, with clinical development of RG7800 being led by Roche with oversight provided by a steering committee with members representing Roche, PTC, and the SMA Foundation.

However, with further clinical development of RG7800 still on hold, in January 2016 the collaborators began a Phase 1 clinical trial in the Netherlands of another SMN2 splicing modifier compound called RG7916.

Based on information from that study, the partners hope to begin clinical trials of RG7916 in people with SMA Type 1 and SMA Type 2/3 by the end of this year. Clinical trial sites, enrollment information, and study timelines will be announced once regulatory feedback has been obtained in countries where the proposed trials will be conducted.

Moonfish study participants will be offered the opportunity to enroll in an open label study with RG7916 provided they meet study criteria. These patients will be contacted by their clinical trial administrator to update them on the new developments.

For more information about updates on the RG7800 and RG7916 studies, visit https://www.clinicaltrialsregister.eu or https://clinicaltrials.gov

or contact the , Information Support Line at 888-662-6728.

The partners say details of the upcoming RG7916 studies will be posted on these websites soon. They note that public participation in clinical trials is critical to the process of advancing scientific understanding of SMA.

According to the research and support organization CureSMA, the disease affects approximately 1 in 10,000 babies, and is the No. 1 genetic cause of death in infants, with about 1 in every 50 Americans a genetic carrier. There is currently no cure for SMA, with treatment consisting of managing the symptoms and preventing complications.

From:http://smanewstoday.com/2016/09/20/sma-drug-rg7800-clinical-trial-on-hold-partners-developing-rg7916