Author: Rachael Hansford

PTC Therapeutics Announces Results from Long-Term AADC Deficiency Gene Therapy Treatment Demonstrating Sustained Improvements

Posted on October 25, 2019 by - Industry News

Results represent five year follow up  

SOUTH PLAINFIELD, N.J., October 24, 2019 – PTC Therapeutics, Inc. today announced new results from its investigational gene therapy, PTC-AADC, in patients living with aromatic L-amino acid decarboxylase (AADC) deficiency. The data demonstrated clinically meaningful and sustained improvements in motor, cognitive and language milestones. These included the ability to sit, walk, and talk and represents up to five years of follow up post-treatment.1,2 PTC-AADC is a one-time gene therapy treatment of the human dopa decarboxylase (DDC) gene administered into the putamen, which supports production of key neurotransmitters. The data were presented at the Child Neurology Society 48th Annual Meeting.

“We are excited to see the transformational effects in AADC deficiency patients in this long-term study as patients with severe AADC deficiency never achieve the ability to sit, walk or talk,” said Stuart Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics. “We are on track to submit a BLA to the FDA by the end of the year and are proud to be on the verge of bringing the first commercial treatment for AADC deficiency patients, which is in line with our mission of bringing clinically differentiated treatments to patients with rare disorders.”

New analysis evaluated outcomes of 26 patients with AADC deficiency across three separate clinical trials,2 making it the most comprehensive analysis of patients treated with PTC-AADC to date. Specifically, these results showed that 12 months post-treatment with PTC-AADC, patients’ mean body weight had increased from 12.0 kg to 15.2 kg, and the frequency of oculogyric crises (involuntary upward eye movement) was reduced.2 Dyskinesia (involuntary movements) was the most frequently recorded adverse event, however most events were mild or moderate and all cases resolved by 10 months post-treatment.2

“In addition to failing to reach key developmental milestones, such as walking and talking, children with AADC deficiency can experience severe symptoms that affect their everyday lives. These symptoms can include episodes of oculogyric crises, which can last for minutes or hours and involve sustained upward movement of the eyes, involuntary movements of the neck, tongue protrusions and jaw spasms, which can be very distressing for patients and their families,” said Claudio Santos, M.D., Senior Vice President, Global Medical Affairs, PTC Therapeutics. “The post-treatment data presented at CNS confirm reductions in the number of patients experiencing oculogyric crises, suggesting that this gene therapy treatment has the potential to make a real difference in the lives of patients with AADC deficiency.”

A separate analysis of a long-term study demonstrated the sustained efficacy of PTC-AADC up to five years.1 These are the longest data available for any investigational treatment for AADC deficiency. These results showed clinically meaningful and sustained improvements in motor, cognitive and language milestones up to five years post-treatment with PTC-AADC.1

An additional abstract building on the existing understanding of AADC deficiency was also presented, giving a disease state overview that highlights the potential importance of a gene therapy to treat this condition.3

About aromatic L-amino acid decarboxylase (AADC) deficiency

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic condition caused by a mutation in the dopa decarboxylase (DDC) gene, resulting in a lack of functioning AADC enzyme, which is responsible for the final step in the synthesis of key neurotransmitters dopamine and serotonin.4

AADC deficiency results in delays or failure to reach developmental milestones such as head control, sitting, standing, walking, or talking, low muscle tone (also known as muscular hypotonia), severe, seizure-like episodes involving involuntary eye movement (also known as oculogyric crises), autonomic abnormalities, and the need for life-long care.4 Given this neurologically devastating illness, patients with severe AADC deficiency have a high risk of death during childhood. There are currently no approved therapies that address the underlying cause.

References:

  1. Chien et al. AGIL-AADC gene therapy results in sustained improvements in motor and developmental milestones through 5 years in children with AADC deficiency. Poster presented at the 48th Annual Meeting of the Child Neurology Society, Oct 23-26, 2019 Charlotte, NC, USA. Poster P207.
  2. Hwu et al. Safety and Improved Efficacy Outcomes in Children With AADC Deficiency Treated with AGIL-AADC Gene Therapy: Results From Three Clinical Trials..  Poster presented at the 48th Annual Meeting of the Child Neurology Society, Oct 23-26, 2019 Charlotte, NC, USA. Poster P231.
  3. Himmelreich et al. Epidemiology, molecular genetics, and new treatment options for aromatic amino acid decarboxylase deficiency..  Poster presented at the 48th Annual Meeting of the Child Neurology Society, Oct 23-26, 2019 Charlotte, NC, USA, Poster P207
  4. Wassenberg et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis. 2017; 12:12.

EMA approves interferon beta treatments, including Rebif (interferon beta-1a), for relapsing MS patients during pregnancy and breastfeeding

Posted on October 22, 2019 by - Industry News

  • EMA approval makes interferon beta, including Rebif (interferon beta-1a), a treatment option for relapsing multiple sclerosis that may be continued into pregnancy if clinically needed and while breastfeeding1,2
  • Approval is based on data from more than 1,000 real-world pregnancy outcomes1
  • MS is most often diagnosed between the ages of 20-40,3 during childbearing years

London – UK, 21 October 2019 – Merck announced that the European Medicines Agency (EMA) has approved an update to the product label of Rebif®, an interferon beta-1a, to include that women with relapsing multiple sclerosis (RMS) may continue treatment with Rebif® (interferon beta-1a) during pregnancy if clinically needed, and also while breastfeeding.1,2

MS is a chronic disease affecting twice as many women as men and is often diagnosed between the ages of 20-40 years.3 A survey of women throughout Europe showed that more than one third of women with MS decided not to have children or altered the timing for having children due to concerns related to their MS.4

The label update has removed the previous contraindication against treatment initiation during pregnancy as well as the requirement to use contraception while on Rebif® (interferon beta-1a). Rebif® (interferon beta-1a) can now also be used during breastfeeding, another important area of unmet need for mothers with MS who wish to breastfeed. According to the new label, levels of interferon beta excreted in breast milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated.1,2

Professor Jeremy Hobart, consultant neurologist at Plymouth Hospitals NHS Trust said: “It’s a win-win for women living with MS. The interferon beta label update represents yet another important step in the history of MS care.  MS is predominantly a disease of women in their childbearing years: juggling the desires for disease control and families has historically been very challenging and deeply troubling for female patients. Now, physicians have more options for treating women with relapsing MS into the beginning of pregnancy and, if clinically needed, during pregnancy and breastfeeding, giving women living with MS – and their clinicians – more confidence that they can have both children and disease control.”

David Martin, Chief Executive Officer of the Multiple Sclerosis Trust added: “MS is most often diagnosed between 20 and 40 years old, at a time when women may be planning to have children. Delaying disease modifying treatment until after having a family can lead to irreversible disability in the long term. Many women living with relapsing MS will be reassured to know that they have the option to start or continue Rebif while pregnant or breastfeeding.”

More than 1,000 pregnancy outcomes from registries and post-marketing experience indicate no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or exposure during the first trimester of pregnancy.1 It should be noted that the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment was likely interrupted when the pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimesters is very limited. Based on animal data, there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.1

About Rebif®

Rebif® (interferon beta-1a) is a disease-modifying drug used to treat relapsing forms of multiple sclerosis (MS) and is similar to the interferon beta protein produced by the human body. The efficacy of Rebif® in chronic progressive MS has not been established. The exact mechanism is unknown.

Rebif®, which was approved in Europe in 1998 and in the US in 2002, is registered in more than 90 countries worldwide.

Rebif® can be administered with the RebiSmart® electronic auto-injection device (not approved in the US), or with the RebiDose® single-use disposable pen. Rebif® can also be administered with the autoinjector Rebiject II® or by manual injection using ready-to-use pre-filled syringes. These injection devices are not approved in all countries.

In January 2012, the European commission approved the extension of the indication of Rebif® in early multiple sclerosis.

Rebif® should be used with caution in patients with a history of depression, liver disease, thyroid abnormalities and seizures. Most commonly reported side effects are flu-like symptoms, injection site disorders, elevation of liver enzymes and blood cell abnormalities. Patients, especially those with depression, seizure disorders, or liver problems, should discuss treatment with Rebif® with their doctors.

About Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common non-traumatic, disabling neurological disease in young adults. It is estimated that approximately 2.3 million people have MS worldwide2, and 100,000 in the UK4. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.

Merck in Neurology and Immunology

Merck has a long-standing legacy in neurology and immunology, with significant R&D and commercial experience in multiple sclerosis (MS). The company`s current MS portfolio includes two products for the treatment of relapsing MS, with a robust pipeline focusing on discovering new therapies that have the potential to modulate key pathogenic mechanisms in MS. Merck aims to improve the lives of those living with MS, by addressing areas of unmet medical needs.

The company`s robust immunology pipeline focuses on discovering new therapies that have the potential to modulate key pathogenic mechanisms in chronic diseases such as MS, systemic lupus erythematosus (SLE) and forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and performance materials. Around 52,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2018, Merck generated sales of € 14.8 billion in 66 countries.

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Performance Materials.

About the Multiple Sclerosis Trust

The Multiple Sclerosis Trust fights to make sure everyone affected by MS can access good quality, specialist care and live the best life they possibly can. It supports and trains MS health professionals and funds MS specialist nurses and Advanced MS Champions across the UK. The MS Trust also produces practical, evidence-based information, online and in print, and its dedicated Enquiry Service team are a friendly and knowledgeable voice to speak to for anyone who needs to know more about MS. To find out more about the MS Trust’s work supporting everyone affected by MS, visit http://www.mstrust.org.uk.

1 https://www.ema.europa.eu/en/documents/procedural-steps-after/rebif-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf

2 https://www.ema.europa.eu/en/medicines/human/EPAR/rebif (accessed 18 October 2019)

3 MS International Foundation. Who Gets MS? https://www.msif.org/about-ms/epidemiology-of-ms/ (accessed 14 October 2019).

4 Merck KGaA, Darmstadt, Germany. The socioeconomic impact of multiple sclerosis on women in Europe. https://www.emdgroup.com/content/dam/web/corporate/non-images/press-releases/2017/oct/us/The-socioeconomic-impact-of-MS-on-women-in-Europe-US.pdf  (14 August 2019)

5 MS Trust. MS in the UK. https://www.mssociety.org.uk/care-and-support/resources-and-publications/publications-search/ms-in-the-uk (accessed 14 October 2019)

New report shows rare disease more common than previously thought

Posted on October 7, 2019 by - Industry News

  • Of all children with epilepsy which starts in the first 3 years of life, one in four are found to have a genetic syndrome
  • Mutations in the CDKL5 gene found to be one of the most common genetic causes of epilepsy in children
  • Previous estimates of a few hundreds of patients in the world with CDKL5 Deficiency Disorder, now replaced by estimates of over 10,000 cases

Approximately one in forty-two thousand children are born with a disease called CDKL5 Deficiency Disorder, according to a new medical report recently published in the journal Brain and presented last month at the 13th European Paediatric Neurology Society Congress in Athens, Greece. This means that each year there are over 100 new children born with the disease in the EU alone, and over 3,000 in the world.

The disease leads to frequent seizures shortly after birth and severe impairment in neurological development, with most affected people being unable to walk, talk or care for themselves. “When our daughter was diagnosed in 2009 they told us there were approximately 200 cases in the world”, says Carol-Anne Partridge, Chair of CDKL5 UK and the International CDKL5 Alliance, which represents patient organisations from 18 countries. “Today we know that these children were simply not being diagnosed correctly,” she adds.

The study, by a medical team from the Royal Hospital for Children in Glasgow, kept track of all births in Scotland during three years and applied genetic testing to all children under 3 years of age who developed epilepsy. “We found that as many as 1 in 4 children with epilepsy have a genetic syndrome”, explains Prof Sameer Zuberi, corresponding author for the study, “and a small group of genes explains most of the cases.”

Among these genes is CDKL5, which encodes a protein necessary for proper brain functioning. Mutations in the CDKL5 gene produce CDKL5 Deficiency Disorder, with one of the first symptoms being early-onset epilepsy. There is no therapy approved for treating the disease now known to affect thousands of people.

But therapies are being developed and the disease has recently attracted much interest from the pharmaceutical industry. There are four clinical trials currently ongoing, and additional companies have announced efforts towards the development of enzyme replacement and gene therapies.

The new disease incidence study highlights the need to increase disease awareness around these genetic disorders previously thought to be much more rare. “Our data suggest that genetic testing should be a primary investigation for epilepsies presenting in early childhood,” explains Prof Sameer Zuberi.

Most of these cases are due to de novo (spontaneous) mutations, so they can occur in any family. But genetic testing is not offered to many patients with early childhood epilepsy and neurodevelopmental disabilities. Because of that, only about 10% of all people living with CDKL5 Deficiency Disorder might have a correct diagnosis.

“These new incidence findings demonstrate that there is still much work to do to diagnose CDKL5 Deficiency Disorder correctly,” explains Daniel Lavery PhD, Chief Scientific Officer of the Loulou Foundation. “As we partner with pharmaceutical companies to develop new therapies and cures for the disorder, we also need to find the thousands of people that are living with this condition so that they can access these new therapies,” he adds.

There is a growing community of researchers from academia and industry with over 500 members working on CDKL5 Deficiency Disorder and organised under the CDKL5 Forum, a project of the Loulou Foundation. The Loulou Foundation also hosts the CDKL5 Forum annual meeting, with this year’s meeting taking place in Boston on November 4th and 5th. The International CDKL5 Alliance recently also held their annual meeting in Edinburgh, Scotland.

The Loulou Foundation and the International CDKL5 Alliance urge the medical community and healthcare leaders to advance policies and protocols to ensure early access to genetic testing to children and adults who experience epilepsy in early childhood.

Article:

Joseph D Symonds, Sameer M Zuberi, et al., (2019), Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort, Brain, https://doi.org/10.1093/brain/awz195

Physioroom.com extends range of services with new online treatment

Posted on September 30, 2019 by - Industry News

PhysioRoom.com, a jargon-explained, sports injury, rehab and fitness website, has partnered with PhysioFast Online (PFO), who offer interactive videocall appointments with qualified physiotherapists to extend its range of services. Launched in 2000, the site offers a wide range of content, empowering users with the knowledge of their own sports injuries in order to supplement treatment and advice given by their doctor. Customers will be able to book an appointment with a qualified physio via www.Physioroom.com or www.physiofastonline.co.uk.

Appointments will normally be available same day to swiftly help reduce suffering and concern and, in many cases, promote a quicker recovery time. A screen share facility ensures that sessions are interactive and personal, whilst 3D human anatomy diagrams help to educate, empower and inform. A downloadable app helps to monitor progress.

Lee Bannister, Head of Customer Experience, said:

Leading research has found that video consultations are as effective as face-to-face appointments and that three in four people can be triaged, assessed and supported online without any need for physical treatment. This collaboration with PFO gives our customers quick and easy access to a team of qualified physios.

Katie Knapton, Founder of PFO, said:

Our service will help to guide patients quickly to the correct rehabilitation treatment and is accessible to anyone with a screen and an internet connection from the comfort of their home, workplace or even overseas. We also offer a complete package of care including referral to imaging if required and a personalised rehab programme.

Interferon Beta Treatments Receive Positive CHMP Opinion for Use in Relapsing Forms of Multiple Sclerosis (MS) During Pregnancy and Breastfeeding

Posted on September 25, 2019 by - Industry News

  • Positive opinion is supported by data from more than 1,000 real-world pregnancy outcomes1,2
  • Data indicate no increased risk of major congenital anomalies after exposure to interferon beta before conception and/or during first trimester1,2
  • Data show pregnancy outcomes are in line with general population1,2

Maidenhead, UK. – 23rd September 2019 – Biogen announced that the Committee for Medicinal Products for Human Use (CHMP) has recommended an update to the marketing authorisations of approved interferon beta treatments, including peginterferon beta-1a and interferon beta-1a, to remove pregnancy contraindications and, where clinically needed, to allow use during pregnancy and breastfeeding in women with relapsing multiple sclerosis (MS).

Women are twice as likely to get MS than men3, with many diagnosed in their twenties and thirties – a time when they may be considering starting a family. The ability to choose a treatment plan that allows women to continue or start their MS therapy while pregnant or breastfeeding is an important step forward for those living with this chronic, debilitating disease, their partners, and their healthcare professionals. We are delighted that the CHMP’s positive opinion, based on data from over 1,000 pregnancy outcomes,1,2 may provide them with greater confidence when considering treatment with peginterferon beta-1a or interferon beta-1a.

Dr. Simon Beck, Medical Director, Biogen UK & Ireland.

The CHMP opinion is based on data from the European Interferon Beta Pregnancy Registry, as well as the national health registers in Finland and Sweden, which together created the largest cohort studies providing safety data related to interferon beta exposure in women of child-bearing age with MS.2

Data collected indicated no increased risk of major congenital anomalies following exposure to interferon beta before conception or during the first trimester of pregnancy.1,2 However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment was likely interrupted when the pregnancy was detected and/or confirmed. Additionally, experience with exposure in the second and third trimesters is very limited.2 The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far.2 Limited data suggest the levels of interferon beta-1a excreted in human milk are negligible, and no harmful effects on the breastfed newborn/infant are anticipated.4, 5

References

1 Prevalence of Infant Outcomes at Birth After Exposure to Interferon Beta Prior to or During Pregnancy: A Register-based Cohort Study in Finland and Sweden Among Women with MS. Presented at: 2019 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, September 13th 2019, Stockholm, Sweden.

2 Hellwig K, Geissbuehler Y, Sabidó M. Pregnancy and Infant Outcomes with Interferon Beta: Data from the European Interferon Beta Pregnancy Registry and MS Pregnancy study conducted in Finland and Sweden. Presented at: 2019 American Academy of Neurology Annual Meeting (AAN). May 4th – 10th, 2019; Philadelphia, PA, USA.

3 Airas L et al. Obstet Med. 2012;5(3):94-97

4 Plegridy (peginterferon beta-1a) draft summary of product characteristics, September 2019

5 Avonex (interferon beta-1a) draft summary of product characteristics, September 2019

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New Research demonstrates Biogen’s continued commitment to improve care of patients with Multiple Sclerosis across treatment spectrum

Posted on September 13, 2019 by - Industry News

  • Data highlight benefits and risks of TYSABRI® (natalizumab) treatment in relapsing remitting multiple sclerosis (RRMS) for achieving NEDA (no evidence of disease activity) and improving disability and cognition1
  • An analysis of data from the TYSABRI Observational Program (TOP) supports real-world effectiveness of extended interval dosing (every six weeks) with natalizumab2
  • Safety was consistent with the natalizumab well-established profile2
  • Additional findings showed exposure to interferon beta, including PLEGRIDY® (peginterferon beta-1a) and AVONEX® (interferon beta-1a), is not expected to impact pregnancy or infant outcomes3, 4

Biogen has highlighted data that support the potential additional effectiveness of treatment with natalizumab, peginterferon beta-1a and interferon beta-1a in RRMS patient populations.1, 2, 3, 4 Results obtained in real-world clinical practice were presented at the 35th Congress of the European Committee for Treatment and 24th Annual Conference of Research in MS (ECTRIMS) in Stockholm (September 11-13).

Biogen’s commitment to improving the lives of people with neurological conditions means that we are always looking for the opportunity to use real word evidence to build a wider picture of multiple sclerosis (MS), beyond clinical trials. Through thoughtful and rigorous exploration of potential new approaches, including natalizumab extended interval dosing and interferon beta treatment before conception and/or during pregnancy, we are using research to evolve the paradigm of care – keeping patients at the centre of our focus.
Dr. Simon Beck, Medical Director, Biogen UK & Ireland

Data Further Support Early Treatment with natalizumab and Extended Interval Dosing

Four-year data from the observational, open-label, single-arm, multicentre STRIVE study in the US support the real-world long-term effectiveness of natalizumab in patients with early RRMS, who are within three years from diagnosis and are anti-JC virus antibody negative.1 Over the first two to four years of treatment (N=110/157), 70.1 percent (95%CI) of patients in the study achieved clinical NEDA (no evidence of disease activity), defined as no relapses or 24-week confirmed disability worsening, which was the primary endpoint.1 Additionally, 83.7 percent (95%CI) achieved MRI NEDA, defined as no gadolinium-enhancing or new/newly enlarging T2 lesions, and more than half (58 percent) achieved overall NEDA, which encompassed both clinical and MRI NEDA.1 Results also show natalizumab was associated with improvements in disability and cognitive performance.1

The effectiveness of every six weeks (Q6W) dosing with natalizumab was evaluated using data from the “TYSABRI Observational Program” (TOP), an ongoing, real-world study of natalizumab-treated patients.

Analyses compared relapse outcomes in patients who switched to natalizumab (Q6W) dosing after at least one year on every four weeks (Q4W) dosing to those who remained on the (Q4W) dosing, which is the current marketing authorisation label dosing.2 After propensity score matching, results indicate there was no significant difference in annualised relapse rate or risk of relapse between the two groups.2 These data complement the previously presented TOUCH database safety analysis showing that natalizumab extended interval dosing (EID; average of approximately six weeks) was associated with a lower risk of the brain infection progressive multifocal leukoencephalopathy (PML), compared to (Q4W) dosing.2, 5 Biogen recently completed enrollment for the Phase 3b NOVA study, a two-year, randomised, prospective trial that will compare the effectiveness of natalizumab (Q4W) versus (Q6W) after at least one year of (Q4W) dosing.

Real-World Data Indicate Interferon Beta Treatment May Not Impact Some Pregnancy/Infant Outcomes

As women with MS are often diagnosed and treated at child-bearing age6, family planning is frequently an important consideration for clinicians and patients when choosing a treatment path. The current marketing authorisation labels indicate that: “There is limited information on the use of Interferon Beta in pregnancy. Available data indicates that there may be an increased risk of spontaneous abortion. Initiation of treatment is contraindicated during pregnancy”.7, 8 New data from two real-world observational studies showed that exposure to interferon beta treatment, including peginterferon beta-1a and interferon beta-1a, before conception and/or during pregnancy is not expected to have an adverse effect on pregnancy or infant growth outcomes.3, 4

Researchers utilised healthcare data from Nordic registers (Finland and Sweden) to retrospectively analyse infant outcomes for women with MS treated with interferon beta compared to women with MS unexposed to disease-modifying therapies. Results show outcomes were similar between the two groups, with no evidence that exposure to interferon beta treatment before and/or during pregnancy affected the weight or head circumference of infants at birth.3 Data on pregnancy outcomes collected during the ongoing five-year “PLEGRIDY Observational Program” (POP), which is evaluating the long-term safety and effectiveness of peginterferon beta-1a in more than 1,200 relapsing MS patients worldwide, were consistent with previously reported pregnancy outcomes from both the Nordic registers study and the European Interferon Beta Pregnancy Registry.3, 4, 9

Featured data presentation details:

  • Natalizumab is Associated with No Evidence of Disease Activity and with Improvement in Disability and Cognitive Performance in Anti–JC Virus Seronegative Patients with Early Relapsing-Remitting Multiple Sclerosis: STRIVE 4-Year Results (P1348; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)
  • No Significant Difference in Relapse Outcomes in Patients Switching to Natalizumab Extended Interval Dosing or Remaining on Standard Interval Dosing: Propensity Score Comparative Effectiveness Analysis of Patients in the TYSABRI Observational Program (P1033, Poster Session 2, Thursday, September 12, 5:15-7:15 p.m. CET)
  • Prevalence of Infant Outcomes at Birth After Exposure to Interferon Beta Prior to or During Pregnancy: A Register-based Cohort Study in Finland and Sweden Among Women with MS (P1144; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)
  • Safety, Pregnancy Outcomes, and Clinical Effectiveness of Peginterferon Beta-1a for Patients with Newly Diagnosed and Non-Newly Diagnosed Relapsing Multiple Sclerosis: Third Interim Analysis of the Plegridy Observational Program (P1019; Poster Session 2, Thursday, September 12, 5:15-7:15 p.m. CET)

Biogen has submitted applications to the European Medicines Agency (EMA) to update products labels with the new data included in this press release

References

1 STRIVE 4-Year Results (P1348; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)

2 Propensity Score Comparative Effectiveness Analysis of Patients in the TYSABRI Observational Program

(P1033, Poster Session 2, Thursday, September 12, 5:15-7:15 p.m. CET)

3 Prevalence of Infant Outcomes at Birth After Exposure to Interferon Beta Prior to or During Pregnancy: A

Register-based Cohort Study in Finland and Sweden Among Women with MS (P1144; Poster Session 3,

Friday, September 13, 12:15-2:15 p.m. CET)

4 Safety, Pregnancy Outcomes, and Clinical Effectiveness of Peginterferon Beta-1a for Patients with Newly

Diagnosed and Non-Newly Diagnosed Relapsing Multiple Sclerosis: Third Interim Analysis of the Plegridy

Observational Program (P1019; Poster Session 3, Friday, September 13, 12:15-2:15 p.m. CET)

5 Reduced Risk of Progressive Multifocal Leukoencephalopathy (PML) Associated with Natalizumab

Extended Interval Dosing (EID): Updated Analysis of the TOUCH® Prescribing Program Database, 71st Annual Meeting of the American Academy of Neurology, Philadelphia, PA. May 4-10, 2019. S26.006.

6 Role of Family Planning in Women With Multiple Sclerosis in Switzerland: Results of the Women With Multiple Sclerosis Patient Survey. Christian P. Kamm et al. 10 October 2018. Frontiers in Neurology.

7 AVONEX 30 micrograms/0.5 ml solution for injection. SmPC.

https://www.medicines.org.uk/emc/product/886/smpchttps://www.medicines.org.uk/emc/product/886/smpc Last accessed: September 2019

8 Plegridy 125 micrograms solution for injection in pre-filled pen. SmPC.

https://www.medicines.org.uk/emc/product/3409/smpchttps://www.medicines.org.uk/emc/product/3409/smpc Last accessed: September 2019

9 Pregnancy and Infant Outcomes with Interferon Beta: Data from the European Interferon Beta Pregnancy Registry and Population Based Registries in Finland and Sweden. Presented at ECTRIMS 2018; 10-12 October; Berlin, Germany. Abstract No. A-0950-0000-02658.

New data from Biogen reinforce long-term benefits of Tecfidera® (Dimethyl Fumarate) over 10 years

Posted on September 13, 2019 by - Industry News

  • TECFIDERA consistently maintained low levels of disease activity with no increased risk in adverse events over a decade of treatment
  • Latest interim data from Phase 3 EVOLVE-MS-1 trial show Biogen and Alkermes’ investigational treatment, diroximel fumarate, was generally well tolerated with low rates of treatment discontinuation over 18 months

September 11th: Biogen announced new data to support the consistent, long-term benefits of treatment with TECFIDERA® (dimethyl fumarate) over 10 years, as well as additional diroximel fumarate data that further characterise the tolerability profile of this investigational oral fumarate for relapsing multiple sclerosis (MS). These findings were presented at the 35th Congress of the European Committee for Treatment and Research in MS (ECTRIMS) and 24th Annual Conference of Rehabilitation in MS in Stockholm (September 11-13).

Biogen’s new data underscore TECFIDERA’s role as a meaningful long-term therapy option for relapsing MS, with many patients in the study experiencing no relapses or progression in their disability over a 10-year period. We are proud of the strong legacy TECFIDERA has achieved over the years and are excited to continue building our franchise of fumarate products with the potential addition of diroximel fumarate. As a next-generation fumarate, diroximel fumarate offers a differentiated gastrointestinal tolerability profile and, if approved, will be a strong choice for physicians and patients with relapsing MS to consider.
Alfred Sandrock, Jr., M.D., Ph.D., executive vice president and chief medical officer at Biogen

TECFIDERA 10-Year Data Support Long-Term Benefits
New results from the ongoing Phase 3 ENDORSE extension study reinforce the long-term effectiveness and safety of continuous TECFIDERA treatment over a decade. In the analysis, which included participants (n= 192) with at least 10 years of follow up, TECFIDERA was associated with a low incidence of MS relapses and disability progression over time. Results show that approximately half (51 percent) of patients remained relapse-free over the study period. In addition, 64 percent of patients had no confirmed disability progression over the study period, and patients generally maintained the ability to walk without significant disability (79 percent). The well-characterised safety profile of TECFIDERA was consistent over 10 years, with no increased occurrence of serious infections.

Separately, a meta-analysis of real-world evidence to compare the effectiveness of TECFIDERA versus other disease-modifying therapies for relapsing MS was also presented. The meta-analysis analysed data from 18 databases of large real-world studies and found that TECFIDERA was significantly more effective than interferon beta, glatiramer acetate and teriflunomide in reducing annualised relapse rate and delaying time to first relapse. TECFIDERA demonstrated comparable effectiveness to fingolimod and was less effective than natalizumab and alemtuzumab. These results are consistent with previously reported comparative effectiveness data and reinforce the strong efficacy of TECFIDERA over platform treatments across multiple data sets.

Data Support Diroximel Fumarate as a Potential New Option for Relapsing MS
Updated interim data from the Phase 3 EVOLVE-MS-1 study support the potential of Biogen and Alkermes’ investigational treatment, diroximel fumarate, as a novel oral fumarate. EVOLVE-MS-1 is an ongoing, single-arm, open-label, two-year study evaluating the safety and exploring the efficacy of diroximel fumarate in patients with relapsing-remitting MS and has enrolled approximately 1,000 patients. The interim results, which included data from 888 patients treated with diroximel fumarate for a median of approximately 18 months, corroborate previous data indicating diroximel fumarate is generally well-tolerated in people with relapsing MS.

In the study, most adverse events were mild to moderate in nature. The overall rate of treatment discontinuation due to adverse events was low (7.1 percent), with less than 1 percent of patients discontinuing diroximel fumarate treatment due to gastrointestinal (GI) side effects. These data are further supportive of recently reported topline results from the elective Phase 3 EVOLVE-MS-2 study, in which diroximel fumarate demonstrated statistically superior GI tolerability compared to TECFIDERA on the study’s primary endpoint assessing self-reported GI events.

Exploratory efficacy results from EVOLVE-MS-1 suggest diroximel fumarate significantly reduced annualised relapse rate by 79.4 percent and the mean number of gadolinium-enhancing lesions by 64.3 percent from baseline to 24 months, with similar results observed in newly diagnosed patients.

Featured data presentation details:

  • Overall Safety and Efficacy Through 10 Years of Treatment with Delayed-release Dimethyl Fumarate in Patients with Relapsing-remitting Multiple Sclerosis (P1397; Poster Session 3, Friday, September 13, 12:15-2:15 pm CET)
  • Comparative Effectiveness of Delayed-release Dimethyl Fumarate vs. Other Disease-modifying Therapies in Patients with Multiple Sclerosis: A Network Meta-analysis of Real-world Evidence (P1394; Poster Session 3, Friday, September 13, 12:15-2:15 pm CET)
  • Diroximel Fumarate (DRF) in Patients with Relapsing-remitting Multiple Sclerosis: Interim Safety and Efficacy Results from the Phase 3 EVOLVE-MS-1 Study (ePoster; available for duration of congress)

About TECFIDERA®
TECFIDERA is the most prescribed oral medication for relapsing multiple sclerosis (MS) in the world and has been shown to reduce the rate of MS relapses, slow the progression of disability and impact the number of MS brain lesions, while demonstrating a well-characterised safety profile in people with relapsing forms of MS. TECFIDERA is approved in 69 countries, and more than 415,000 patients have been treated with it, representing more than 780,000 patient-years of exposure across clinical trial use and patients prescribed TECFIDERA. Of these, 6,335 patients (14,065 patient-years) were from clinical trials.1

TECFIDERA is contraindicated in patients with a known hypersensitivity to dimethyl fumarate or any of the excipients of TECFIDERA. Rare cases of progressive multifocal leukoencephalopathy, a rare opportunistic viral infection of the brain which has been associated with death or severe disability, have been seen with TECFIDERA patients in the setting of prolonged lymphopenia although the role of lymphopenia in these cases is uncertain. Other serious side effects include a decrease in mean lymphocyte counts during the first year of treatment, which then plateaued, and liver function abnormalities, which resolved upon treatment discontinuation. In clinical trials, the most common adverse events associated with TECFIDERA were flushing and gastrointestinal (GI) events.

About Diroximel Fumarate
Diroximel fumarate is an investigational, novel oral fumarate candidate with a distinct chemical structure in development for the treatment of relapsing forms of MS. Diroximel fumarate is designed to rapidly convert to monomethyl fumarate in the body and, based on bioequivalence data, is referencing TECFIDERA® (dimethyl fumarate) as part of the 505(b)(2) regulatory pathway in the United States. Diroximel fumarate is currently under review with the U.S. Food and Drug Administration (FDA) with a PDUFA (Prescription Drug User Fee Act) target action date in the fourth quarter of 2019. If approved by the FDA, Biogen intends to market diroximel fumarate under the conditionally approved brand name VUMERITY™.

Roche’s satralizumab significantly reduced relapse risk in second positive phase III study for neuromyelitis optica spectrum

Posted on September 13, 2019 by - Industry News

  • Pivotal phase III SAkuraStar study shows 55% reduction in the risk of relapse for satralizumab monotherapy versus placebo presented at ECTRIMS 2019
  • 74% reduction in the risk of relapse for satralizumab monotherapy versus placebo in people with neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibodies (AQP4-IgG seropositive patients)
  • Satralizumab demonstrated a similar safety profile compared to placebo in two phase III studies across a broad population
  • Satralizumab targets the interleukin-6 (IL-6) receptor, a key driver of NMOSD

On 12th September Roche presented full pivotal phase III study results for satralizumab as a monotherapy for neuromyelitis optica spectrum disorder (NMOSD), a rare, debilitating central nervous system disease. Results from the SAkuraStar study  show that satralizumab monotherapy achieved a 55% reduction in the risk of relapses compared to placebo in the overall population, representative of NMOSD patients (HR 0.45, 95% CI: 0.23-0.89; p=0.0184). In the large (~67%) subgroup of patients seropositive for AQP4-IgG antibodies, the effect was higher with a 74% reduction in risk of relapses (HR 0.26, 95% CI: 0.11-0.63; p=0.0014). People who are AQP4-IgG seropositive tend to experience a more severe disease course.

The positive phase III results for satralizumab, first as an add-on therapy and now as a monotherapy are exciting to see, and importantly, it achieved efficacy in a broad range of NMOSD patients, reflective of what we see in our everyday practice. Satralizumab targets the IL-6 receptor, potentially offering a novel treatment approach. Approved treatment options demonstrating favourable safety and efficacy in controlled clinical trials are urgently needed. Even one relapse may lead to blindness and debilitating motor dysfunction for people with NMOSD.
Professor Jeffrey Bennett, University of Colorado Neurology & Ophthalmology

In the overall satralizumab-treated population, 76.1% were relapse-free at 48 weeks, and 72.1% relapse-free at 96 weeks, compared to 61.9% and 51.2% with placebo, respectively. Data from the AQP4-IgG seropositive subgroup showed that 82.9% were relapse-free at 48 weeks and 76.5% relapse-free at 96 weeks when treated with satralizumab, compared to 55.4% and 41.1% with placebo, respectively.

NMOSD is commonly associated with pathogenic antibodies (AQP4-IgG) that target and damage a specific cell type, called astrocytes, resulting in inflammatory lesions of the optic nerve(s), spinal cord and brain. Through the use of a diagnostic biomarker test, most NMOSD patients are identified as AQP4-IgG seropositive; however, as many as one-third of patients with NMOSD are AQP4-IgG seronegative. The condition is often misdiagnosed as multiple sclerosis.

Satralizumab inhibits IL-6 signalling, which is believed to play a key role in the inflammation that occurs in people with NMOSD, leading to damage and disability. People with NMOSD experience unpredictable, severe relapses that directly cause cumulative, permanent neurological damage.

“While first described 125 years ago, the underlying biology of NMOSD has only recently been understood. The positive results from the pivotal SAkuraStar and SAkuraSky studies support the hypothesis that IL-6 plays a key role in this devastating disease that can take away people’s independence,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “We are encouraged by these results and look forward to working with regulators over the coming months to bring satralizumab to people living with NMOSD as soon as possible.”

These SAkuraStar data add to the previously reported results for satralizumab in combination with baseline therapy for people with NMOSD. Initial phase III data for SAkuraSky were presented at the 34th ECTRIMS congress in 2018. The data showed a 62% reduction in the risk of relapses in a representative population of both AQP4-IgG seropositive and AQP4-IgG seronegative patients in the overall study population (HR 0.38, 95% CI: 0.16-0.88; p=0.0184) when used in combination with baseline therapy compared to placebo, and a 79% reduction in the risk of relapses in AQP4-IgG seropositive patients (HR 0.21, 95% CI: 0.06-0.75; p=0.0086).

Overall, the proportion of patients with serious adverse events was similar between the satralizumab monotherapy and placebo treatment groups in the SAkuraStar study; and between the satralizumab added to baseline therapy and placebo added to baseline therapy treatment groups in the SAkuraSky study. A lower rate of infections (including serious infections) was observed in patients treated with satralizumab compared with the placebo group. In both studies, most adverse events were mild to moderate, and the most common adverse events in the satralizumab group were urinary tract infections and upper respiratory tract infections in the SAkuraStar study and upper respiratory tract infections, nasopharyngitis (common cold) and headache in the SAkuraSky study. Safety analyses continue in the open-label extensions of SAkuraStar and SAkuraSky.

The data available across two controlled, randomised phase III clinical trials suggest that satralizumab could be an efficacious option for patients across a broad NMOSD patient population, whether given as a monotherapy or in combination with baseline therapy. Satralizumab is administered every four weeks by subcutaneous injection, which may be a convenient option for patients and carers.

The SAkuraStar study recruited 95 NMOSD patients from the age of 20-70 and SAkuraSky recruited 83 patients, including adolescents, aged 13-73. These studies represent one of the largest clinical trial programmes undertaken for this rare disease.

About SAkuraStar and SAkuraSky in NMOSD

SAkuraStar is a phase III multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of satralizumab monotherapy administered to patients with NMOSD. The primary endpoint is the time to first protocol-defined relapse (PDR), adjudicated by an independent review committee in the double-blind period. Secondary endpoints included the Visual Analogue Scale (VAS) score for pain and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score.

Ninety-five patients aged from 20-70 years were randomised to either of the following two treatment groups in a 2:1 ratio: satralizumab (120 mg) or placebo. Both treatments were administered subcutaneously at Week 0, 2, and 4. The subsequent treatment was continued at 4-week intervals. The double-blind treatment period ended when the total number of PDRs had reached 44 or at 1.5 years after the enrollment of the last patient, whichever occurred first. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with satralizumab in an open-label extension period. Patients with AQP4-IgG seropositive or seronegative neuromyelitis optica (NMO, as defined by the diagnostic criteria in 2006) and those with AQP4-IgG seropositive NMOSD were enrolled.

SAkuraSky is a phase III multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of satralizumab added to baseline immunosuppressant therapy in patients with NMOSD. The primary endpoint was the time to first relapse as adjudicated by an independent review committee in the double-blind period. Main secondary endpoints included change in VAS score for pain and change in FACIT Fatigue score.

Eighty-three male and female patients aged from 13 to 73 years were randomised to either of the following two treatment groups in a 1:1 ratio: satralizumab (120 mg) or placebo added to baseline therapy (azathioprine, mycophenolate mofetil and/or corticosteroids). Both treatments were administered subcutaneously at Week 0, 2, and 4. The subsequent treatment was continued at 4-week intervals. The double-blind treatment ended when patients experienced a PDR; the study ended when the total number of PDRs reached 26. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with satralizumab in an open-label extension period. Patients with AQP4-IgG seropositive or seronegative neuromyelitis optica (NMO, as defined by diagnostic criteria in 2006) and those with AQP4-IgG seropositive NMOSD were enrolled.

About neuromyelitis optica spectrum disorder (NMOSD)

NMOSD is a rare, lifelong and debilitating autoimmune disease of the central nervous system that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis. People with NMOSD experience unpredictable, severe relapses directly causing cumulative, permanent, neurological damage and disability. In some cases, relapse can result in death. NMOSD affects over 10,000 people in Europe, 15,000 people in the US and up to hundreds of thousands of people worldwide. The disease is most common among non-Caucasian women in their 30s and 40s.

NMOSD is commonly associated with pathogenic antibodies (AQP4-IgG) that target and damage a specific cell type, called astrocytes resulting in inflammatory lesions of the optic nerve(s), spinal cord and brain. AQP4-IgG antibodies are detectable in the blood serum of around two-thirds of NMOSD patients.

Although most cases of NMOSD can be confirmed through a diagnostic test, people living with the condition are still frequently misdiagnosed with multiple sclerosis. This is due to overlapping features of the two disorders, including a higher prevalence in women, similar symptoms and the fact that both are relapse-based conditions.

New Real-World Data Support Long-Term Efficacy and Safety Profile of MAVENCLAD®

Posted on September 13, 2019 by - Industry News

Post-hoc analysis found 75% of patients from CLARITY and CLARITY Extension showed no disability progression at five years post-treatment

No new safety findings from up to 10 years of clinical programme follow-up and post-approval data following the launch of MAVENCLAD in 2017

Merck announced the presentation of new data for MAVENCLAD® (cladribine tablets), which further characterise the long-term efficacy and safety profile. These data were shared at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place from 11–13 September, 2019, in Stockholm, Sweden.

Our commitment to further understand the long-term efficacy and safety of MAVENCLAD goes beyond the safety profile seen in its clinical development programme, which includes up to 10 years of safety follow-up in some patients. The data we are presenting at ECTRIMS 2019 exemplify this. They include key insights from real-world follow-up of patients from our clinical trials and the post-approval setting for MAVENCLAD, further validating it as an important treatment option available to patients in 69 countries worldwide.
Luciano Rossetti, Head of Global Research & Development for the biopharma business of Merck 

Results from a post hoc analysis (EP1573) evaluating five-year disease stability demonstrated sustained efficacy of cladribine tablets on disability progression, as measured by the Expanded Disability Status Scale (EDSS). According to study findings, 75% of patients showed stable or improved EDSS at five years post-treatment. The exploratory analysis was based on patients treated with cladribine tablets in CLARITY and then placebo in CLARITY Extension, with at least one post-baseline EDSS measurement.

Results were presented from a retrospective analysis (P617) of real-world follow-up data from an Italian multiple sclerosis (MS) registry, consisting of patients with clinically isolated syndrome or relapsing forms of MS who received at least one course of MAVENCLAD in the original clinical trial programme. At five years after receiving the last dose of MAVENCLAD, nearly two-thirds of patients (64%) had no disability progression and more than half of the patients (57%) were free of relapse.

These data show us that MAVENCLAD continues to display sustained efficacy in a majority of patients at five years after starting treatment and that these results are consistent with data we are seeing from real-world experience. As a neurologist, this is important for me to see, as it shows that findings from the clinical development programme of MAVENCLAD will be borne out in clinical practice.
Prof. Gavin Giovannoni, a lead investigator in the CLARITY studies and Chair of Neurology, Barts and The London School of Medicine and Dentistry

In addition, final results (P1390) from the PREMIERE safety registry allowed for a thorough characterisation of the long-term safety profile of MAVENCLAD and showed no new safety findings. Furthermore, post-marketing data in the first 8,419 patients treated with MAVENCLAD worldwide were consistent with the safety profile seen in the MAVENCLAD clinical development programme, with no increase in incidence of adverse events from original clinical programme findings.

*About MAVENCLAD®

MAVENCLAD® is a short-course oral therapy that selectively and periodically targets lymphocytes thought to be integral to the pathological process of relapsing MS (RMS). In August 2017, the European Commission (EC) granted marketing authorization for MAVENCLAD® for the treatment of relapsing forms of multiple sclerosis (RMS) in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. MAVENCLAD® has since then been approved in 69 countries, including Canada, Australia and the U.S. Refer to the respective prescribing information for further details.

The clinical development programme for cladribine tablets includes:

The CLARITY (Cladribine Tablets Treating MS Orally) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients with RRMS.

The CLARITY extension study: a Phase III placebo-controlled study following on from the CLARITY study, which evaluated the safety and exploratory efficacy of cladribine tablets over two additional years beyond the two-year CLARITY study, according to the treatment assignment scheme for years 3 and 4.

The ORACLE MS (Oral Cladribine in Early MS) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS).

The ONWARD (Oral Cladribine Added ON to Interferon beta-1a in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled study designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy.

PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis) study: a long-term observational follow-up safety registry of MS patients who participated in cladribine tablets clinical studies.

In the two-year CLARITY study, the most commonly reported adverse event (AE) in patients treated with cladribine tablets was lymphopenia (26.7% with cladribine tablets and 1.8% for placebo). The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% respectively rated mild-to-moderate by investigators. Adverse Events reported in other clinical studies were similar.