BPG BLOG2

Rare Disease Highlight: Stargardt Disease
by Rare Disease Highlight

Stargardt Disease, also known as juvenile macular degeneration, is a rare disease of the eyes in which part of the eye called the retina does not function correctly. This is the most common form of inherited macular degeneration, affecting about 30,000 people in the United States2. Stargardt’s is a genetic disease caused by a change in the gene ABCA4, which affects how the body uses vitamin A (retinol)4. Normally, vitamin A is helpful to vision because it maintains a clear cornea and is crucial in allowing us to see in low lighting. As a result, fatty materials build up in the part of the eye called the macula, which is a very small part of the retina responsible for seeing sharp images that are straight ahead4. This disease usually starts in childhood but some people do not experience loss of vision until adulthood. Since central vision is compromised, these patients rely on their peripheral vision for most of their sight. Individuals with this disease experience loss of vision, often have trouble going from light to dark places, or have a higher sensitivity to light4. These patients are unable to drive, have trouble reading normal size print, and struggle identifying facial features5. There is no current treatment for Stargardt Disease. Visual aids such as glasses, magnifiers, and wearable visual devices are helpful for these patients, as well as auditory features such as Siri, talk-to-text, and audiobooks1. Even with these aids, patients are not able to see with 20/20 vision, drive a car, or adjust for light sensitivity. This encourages development of new therapies for Stargardt Disease.

References

  1. American Academy of Opthamology. (2022). Resources and Links for People with Low Vision. Retrieved 8/23/22 from https://www.aao.org/eye-health/diseases/low-vision-resources
  2. Foundation Fighting Blindness. (2022). Stargardt Disease. Retrieved 8/19/2022 from https://www.fightingblindness.org/diseases/stargardt-disease#:~:text=Stargardt%20Disease%20is%20the%20most,the%20retina%20called%20the%20macula.
  3. Healthline. (2018). The 9 Most Important Vitamins for Eye Health Retrieved 8/24/22 from https://www.healthline.com/nutrition/eye-vitamins#:~:text=Vitamin%20A,low%20light%20conditions%20(%201%20).
  4. National Eye Institute. (2021). Stargardt Disease. Retrieved 8/19/2022 from https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/stargardt-disease#:~:text=Stargardt%20disease%20is%20a%20rare,vision%20until%20they’re%20adults.
  5. National Library of Medicine. (2010). Stargardt Macular Degeneration. Retrieved 8/23/22 from https://medlineplus.gov/genetics/condition/stargardt-macular-degeneration/

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

BPG BLOG (11)

ALX Oncology’s Evorpacept Receives Fast Track Designation from FDA as First-Line Treatment for Head and Neck Squamous Cell Carcinoma
by BPG Blog

SOUTH SAN FRANCISCO, Calif., Aug. 01, 2022 (GLOBE NEWSWIRE) — ALX Oncology Holdings Inc., (“ALX Oncology”) (Nasdaq: ALXO) a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, today announced that the U.S. Food and Drug Administration (“FDA”) has granted Fast Track designation to evorpacept, a next generation CD47 blocker, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, for the first-line treatment of adult patients with PD-L1 positive advanced head and neck squamous cell carcinoma (“HNSCC”).

The FDA’s decision is informed by the results of ALX Oncology’s phase 1 clinical trial, ASPEN-01, that showed preliminary antitumor activity and a favorable safety profile in checkpoint inhibitor-naïve patients with second-line or greater advanced HNSCC treated with evorpacept and pembrolizumab (n=10). The preliminary objective response rate of 40% in this limited population represents an improvement over historical anti-PD-1 monotherapy activity in a similar population and supported the initiation of the ASPEN-03 (NCT04675294) study in May 2021 in collaboration with Merck (known as MSD outside the US and Canada). ASPEN-03 is a randomized phase 2 multi-center study to investigate the anti-tumor efficacy of evorpacept plus pembrolizumab in patients with first-line metastatic or unresectable, recurrent PD-L1 positive HNSCC.

“The FDA’s Fast Track designation for the first-line treatment of HNSCC with evorpacept in combination with pembrolizumab builds upon evorpacept’s prior Fast Track designation in the first-line HNSCC population in combination with pembrolizumab and standard chemotherapy highlighting the potential clinical utility of evorpacept in this difficult-to-treat disease,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. “We are pleased by the patient enrollment progress being made across our HNSCC phase 2 program (NCT04675294; NCT04675333) as we seek to advance evorpacept to help patients living with this disease.”

Click here to read the full article at GlobeNewswire

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

BPG 1

FDA Accepts Biogen’s New Drug Application and Grants Priority Review of Tofersen for a Rare, Genetic Form of ALS
by BPG Blog

CAMBRIDGE, Mass., July 26, 2022 (GLOBE NEWSWIRE) — Biogen Inc. (Nasdaq: BIIB) today announced that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for tofersen, an investigational drug for superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). The application has been granted priority review and given a Prescription Drug User Fee Act action date of January 25, 2023. The FDA has noted that it is currently planning to hold an Advisory Committee meeting for this application, on a yet-to-be determined date. The average life expectancy for people with ALS is three to five years from time of symptom onset. There is currently no treatment targeted for SOD1-ALS.2  

“The available data show that tofersen has the potential to make a meaningful difference for people with SOD1-ALS,” said Priya Singhal, M.D., M.P.H., Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “Pursuing the FDA’s accelerated approval pathway offers the potential to make tofersen available to people living with this fatal, neurodegenerative disease as quickly as possible. If approved, tofersen will be the first treatment to target a genetic cause of ALS and we hope this will pave the way for further advances in this relentless disease.”

Biogen is seeking approval of tofersen under the FDA’s accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. Neurofilaments are normal proteins found in healthy neurons, that are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival.3 Tofersen study results suggest reductions in neurofilament preceded and predicted slowing of decline in measures of clinical and respiratory function, strength, and quality of life. Biogen is committed to ongoing data generation and finalizing the confirmatory data package with the FDA.

Click here to read the full article at Biogen

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

BPG

Rare Disease Highlight: Netherton Syndrome
by Rare Disease Highlight

Netherton syndrome (NS), also referred to as bamboo hair syndrome, is a rare and severe genetic skin disorder [1-3]. The disease is characterized by chronic ichthyosiform erythroderma (a condition of fine white and red scales across the entire body), atopy (a genetic tendency to develop allergic diseases), and trichorrhexis invaginate (a distinctive hair disorder known as bamboo hair) [1, 2, 4, 5].

NS is a hereditary disorder that arises from a loss-of-function mutation to the serine protease inhibitor Kazal-type 5(SPINK5) gene, which leads to the clinical features of the disease. This type of mutation results in a deficiency of the lympho-epithelial kazal type inhibitor (LEKTI) and increase of specific enzymes known as proteases, such as kallikrein 7 (Klk7) and enzyme elastase 2 (ELA2), and structural components of the outer layer of the skin, such as pro-filgarrin [6]. These molecules are involved in the balance of fatty acids in the skin, natural peeling of the outer layer skin, activation of the inflammatory process, and structure of the skin [7-11]. Thus, the consequential dysregulation results in the breakdown of the skin barrier [2, 6, 12]. NS is transmitted from parents to their children in an autosomal recessive manner. Autosomal refers to genes located on non-sex chromosomes, such as SPINK5. Each chromosome has two working copies of a gene, inherited from each parent. In recessive genetic diseases, both mutated copies of the gene are needed to induce the disease. Therefore, children must receive a faulty gene from each of their parents for NS to become apparent.

Currently, there are about 150 cases of NS reported in the literature, but the true population size is expected to be higher due to difficulties in diagnosis and overlapping of symptoms with other conditions. Since NS is a hereditary disorder generally observed at birth, newborns and infants are the most vulnerable [13]. This patient population fails to thrive in the first year of life. Specifically, newborns with NS manifesting generalized and severe inflammation of the entire skin surface, referred to as congenital ichthyosiform erythroderma (CIE), experience 10-40% mortality in the first year of life. The increased mortality is due to skin barrier disturbances enhancing the risk of infections and hypernatremic dehydration, a form a dehydration where there is too much sodium in the blood [14-16]. Young NS patients also suffer from growth retardation and short stature due to recurrent infections and inflammation [4]. As the patient grows older, the skin disease gradually regresses into a milder form, referred to as ichthyosis linearis circumflexa (ILC). ILC is characterized by recurrent red plaques on the skin with a double scaling edge. Other allergic symptoms caused by NS include asthma, sneezing, congestion, and itchy nose, eczema (a skin condition characterized by dry, itchy, and inflamed skin), and frequent sensitizations to airborne or food allergens [4, 17].

Currently, no satisfactory treatments are approved for NS. Varying success is observed when patients are treated with topical corticosteroids, topical calcineurin inhibitors, topical retinoids, narrowband ultraviolet B phototherapy, ultraviolet radiation, and oral acitretin. For patients with severe disease, intravenous immunoglobulin and anti-tumor necrosis factor-alpha (TNF-α) antibodies may be used [12]. Overall, based on the clinical severity and limited treatments available to effectively treat manifestations of NS, novel therapies for this patient population are needed to address the unmet medical need.

References

1.           OMIM. Netherton Syndrome; NETH. 2012  [cited 2012; Available from: https://www.omim.org/entry/256500.

2.           Leclerc-Mercier, S., et al., Skin Biopsy in Netherton Syndrome: A Histological Review of a Large Series and New Findings. Am J Dermatopathol, 2016. 38(2): p. 83-91.

3.           NIH. Netherton Syndrome. 2019  08/08/2019]; Available from: https://ghr.nlm.nih.gov/condition/netherton-syndrome#statistics.

4.           Hovnanian, A., Netherton syndrome: new advances in the clinic, disease mechanism and treatment AU – Hovnanian, Alain. Expert Review of Dermatology, 2012. 7(1): p. 81-92.

5.           OMIM. Netherton Syndrome. 2019  08/08/2019]; Available from: https://omim.org/entry/256500.

6.           Bonnart, C., et al., Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. J Clin Invest, 2010. 120(3): p. 871-82.

7.           Elias, P.M., Y. Hatano, and M.L. Williams, Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. J Allergy Clin Immunol, 2008. 121(6): p. 1337-43.

8.           Caubet, C., et al., Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J Invest Dermatol, 2004. 122(5): p. 1235-44.

9.           Hachem, J.P., et al., Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol, 2005. 125(3): p. 510-20.

10.         Nylander-Lundqvist, E., O. Back, and T. Egelrud, IL-1 beta activation in human epidermis. J Immunol, 1996. 157(4): p. 1699-704.

11.         Brattsand, M. and T. Egelrud, Purification and characterization of interleukin 1 beta from human plantar stratum corneum. Evidence of interleukin 1 beta processing in vivo not involving interleukin 1 beta convertase. Cytokine, 1998. 10(7): p. 506-13.

12.         Saleem, H.M.K., et al., Netherton Syndrome: A Case Report and Review of Literature. Cureus, 2018. 10(7): p. e3070-e3070.

13.         NORD. Ichthyosis, Netherton Syndrome. 2005  08/08/2022]; Available from: https://rarediseases.org/rare-diseases/ichthyosis-netherton-syndrome/#:~:text=Netherton%20syndrome%20is%20a%20rare,as%20an%20autosomal%20recessive%20trait.

14.         Stoll, C., et al., Severe hypernatremic dehydration in an infant with Netherton syndrome. Genet Couns, 2001. 12(3): p. 237-43.

15.         Di, W.L., et al., Ex-vivo gene therapy restores LEKTI activity and corrects the architecture of Netherton syndrome-derived skin grafts. Mol Ther, 2011. 19(2): p. 408-16.

16.         Hoeger, P.H. and J.I. Harper, Neonatal erythroderma: differential diagnosis and management of the “red baby”. Archives of Disease in Childhood, 1998. 79(2): p. 186.

17.         Sun, J.D. and K.G. Linden, Netherton syndrome: a case report and review of the literature. Int J Dermatol, 2006. 45(6): p. 693-7.

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with a unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.

BPG BLOG (6)

Ionis announces that FDA accepts New Drug Application and grants Priority Review of tofersen for a rare, genetic form of ALS
by BPG Blog

CARLSBAD, Calif., July 26, 2022 /PRNewswire/ — Ionis Pharmaceuticals (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for tofersen, an investigational antisense medicine for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS). The NDA was submitted by Biogen, which licensed tofersen from Ionis in 2018. The application has been granted priority review and given a Prescription Drug User Fee Act action date of Jan. 25, 2023. The FDA has noted that it is currently planning to hold an Advisory Committee meeting for this application. The average life expectancy for people with ALS is three to five years from time of symptom onset; patients with some SOD1 mutations have an even shorter life expectancy. There is currently no treatment targeted for SOD1-ALS. 

“Acceptance of the new drug application for tofersen is a monumental milestone, not just for Ionis but for all people with SOD1-ALS, their families and healthcare professionals battling this devastating disease. To them we extend our deepest gratitude. Their courage has been instrumental to the achievement of this goal,” said C. Frank Bennett, Ph.D., executive vice president, chief scientific officer and franchise leader for neurological programs at Ionis. “We also want to thank Biogen for their commitment to advancing tofersen, which, if approved, will be the first treatment that targets a genetic cause of ALS.” Dr. Bennett added, “Acceptance of the NDA for tofersen further strengthens Ionis’ platform strategy to target all forms of ALS and central nervous system disorders more broadly.”

Biogen is seeking approval of tofersen under the FDA’s accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. Neurofilaments are normal proteins found in healthy neurons, that are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival. Tofersen study results suggest reductions in neurofilament preceded and predicted slowing of decline in measures of clinical and respiratory function, strength and quality of life. Biogen has stated its commitment to ongoing data generation and finalizing the confirmatory package with the FDA.

Click here to read the full article at Ionis

Disclaimer: BioPharma Global is not responsible for, and expressly disclaims all liability for, damages of any kind arising out of use, reference to, or reliance on any information contained within the article. Content available through the site may contain links and information to other websites. Links from BioPharma Global to third-party sites do not constitute an endorsement by BioPharma Global of the mentioned parties.

BioPharma Global is a mission-driven corporation dedicated to using our FDA and EMA regulatory expertise and knowledge of various therapeutic areas to help drug developers advance treatments for the disease communities with unmet medical needs. If you are a drug developer seeking regulatory support for Orphan Drug designation, Fast Track designation, Breakthrough Therapy designation, other FDA/EMA expedited programs, type A, B (pre-IND, EOPs), or C meeting assistance, or IND filings, the BioPharma Global team can help. Contact us today to arrange a 30-minute introductory call.