novel therapies Archives

Autism Spectrum Disorder (ASD) is a developmental disability that can cause significant social, communication, and behavioral challenges. People with ASD may communicate, interact, behave, and learn in ways that are different from most other people. The learning, thinking, and problem-solving abilities of people with ASD can range from gifted to severely challenged. They might repeat certain behaviors and might not want to change in their daily activities. Many people with ASD also have different ways of learning, paying attention, or reacting to things. A diagnosis of ASD now includes several conditions that used to be diagnosed separately i.e., autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome. These conditions are now knowns as an autism spectrum disorder.

According to the U.S. Centers for Disease Control and Prevention (CDC) approximately, 1 in 68 children in the United States have been diagnosed with Autism. Autism is the third most common developmental disability. According to one of the epidemiological studies by “Action for Autism”, the prevalence rate is 1.7 million (estimated rate of 1 in 250 children). It is most frequent among the boys in comparison to the girls.

There is currently no approved drug on the market that treats the core symptoms of Autism. Hence, there are various pharmaceutical companies have the potential to transform the existing market by developing robust pioneering pipeline clinical programs to treat Autism spectrum disorder. Several companies such as Otsuka Pharmaceutical, Nobelpharma, GW Research Ltd, Hoffmann-La Roche, Allergan & Curemark are developing novel therapies.

Otsuka Pharmaceutical (Brexpiprazole)

Brexpiprazole is a molecule discovered by Otsuka and co-developed by Otsuka and Lundbeck. The efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT₁A and dopamine D₂ receptors, and antagonist activity at serotonin 5-HT₂A receptors. Brexpiprazole exhibits high affinity (subnanomolar) for these receptors as well as for noradrenaline alpha1B/2C receptors.

Brexpiprazole, is currently study under the clinical trial of Phase III. The purpose of this study is to find out about the potential benefits and safety of brexpiprazole in children and adolescent subjects, aged 5 to 17, with irritability associated with autism spectrum disorder.

GW Research Ltd (GWP42006/CBDV)

GWP42006 is the non-psychoactive cannabinoid cannabidivarin (CBDV) extracted from the cannabis plant. It has been evaluating GWP42006 in both general and syndromic pre-clinical models of ASD yielding promising signals on cognitive and social endpoints as well as repetitive behavior. These include both genetically determined abnormalities of neurobehavioral and chemically-induced models. A Phase IIa proof of concept study of a pipeline compound GWP42006 is being evaluated to treat ASD.

Hoffmann-La Roche (Balovaptan)

Balovaptan (RG7314) is a potent and specific small molecule antagonist of the V1A vasopressin receptor, which is implicated in modulating emotional processing and key social deficits exhibited in patients with Autism Spectrum Disorders. A phase III clinical trial is evaluating balovaptan for the treatment of patients with autism spectrum disorder.

Hoffmann-La Roche (RG7816)

RG7816 is a small molecule highly selective positive allosteric modulator of the GABAA α5 receptor, which is expressed in key brain regions for autism spectrum disorder.

Allergan (Cariprazine)

Cariprazine has a high affinity for Dopamine D3 receptors acting as a partial agonist at D3 receptors. Cariprazine is primarily metabolized by CYP3A4 into Desmethyl Cariprazine (DCAR) and DCAR is then further metabolized by CYP3A4 into Didesmethyl Cariprazine (DDCAR). Cariprazine, is evaluated under the clinical study of Phase-I. This study would be a multi-center, open-label, parallel-group, multiple-dose study in up to 24 male and female participants aged 5 through 17 years, inclusive, with Autism Spectrum Disorder (ASD)

Curemark (CM-AT)

CM-AT, is lead drug candidate, is designed to enhance protein digestion thereby potentially restoring the pool of essential amino acids. Essential amino acids play a critical role in the expression of several genes important to neurological function and serve as precursors to key neurotransmitters such as serotonin and dopamine.CM-AT has completed enrollment in The Blüm Study, a Phase III clinical trial for CM-AT in children aged 3-8 years old. CM-AT has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). FDA has also granted Curemark a rolling review of its New Drug Application for CM-AT.

Autism Spectrum Disorder (ASD) Pipeline Landscape

Company Name	Product Name	Stage of Development	Mechanism of Action	Route of Administration
Otsuka Pharmaceutical	Brexpiprazole/OPC-34712/ LuAF41156	Phase III	Dopamine D2 Receptor Partial agonists; Serotonin 1A Receptor Partial Agonists	Oral
Nobelpharma	NPC-15 Granules	Phase II/III	_	oral
GW Research Ltd	GWP42006/ CBDV	Phase II	Cannabinoid Receptor Modulators	Oral
Hoffmann-La Roche	Balovaptan/RO5285119/RO7017773	Phase III	Antagonist of the V1A Vasopressin Receptor	Oral
Hoffmann-La Roche	RG7816	Phase I	–	_
Allergan	Cariprazine	Phase I	CYP3A4 Inhibitor	Oral
Curemark	CM-AT	Phase III	Enzyme Modulators	Oral

Vitiligo is a chronic disorder that causes areas of skin to lose color. When skin cells that make color are attacked and destroyed, the skin turns a milky-white color. Various factors such as autoimmune disease, genetic factors, & neurogenic factors lead to the development of Vitiligo. The main symptom associated with vitiligo is the loss of natural color. The patches can show up on any part of your body and can affect the skin, which gets milky-white patches, usually on the hands, feet, arms, and face, hair, which can turn white on the scalp, eyebrow, eyelash, and beard & the inside of your mouth or nose. People with vitiligo can also get problems with the eyes and ears. In addition, people with the disorder may worry about how their skin looks, which can affect general well-being.

Vitiligo is the most common skin depigmentation disorder with an average prevalence estimated to be between 0.5% to 2% of the global population. An estimated 65-95 million people of all ages, sexes, and ethnicities worldwide suffer from vitiligo, including approximately 2.4 million people in the United States. The majority (70–80%) of patients with vitiligo experience disease onset before age 30. Approximately 30% have childhood-onset vitiligo before age 12.

Currently, there are no FDA-approved therapies for vitiligo. Dermatologists typically prescribe topical corticosteroids, topical calcineurin inhibitors, and/or phototherapy for the treatment of vitiligo. Therefore, pharmaceutical companies such as Incyte Corporation, Dermavant Sciences GmbH, Aclaris Therapeutics, Inc. Amgen and other companies are developing novel therapies for the treatment of Vitiligo.

Incyte Corporation (Ruxolitinib/INCB018424)

Ruxolitinib is a Janus kinase (JAK1/JAK2) inhibitor discovered by Incyte scientists. Overactive signaling through the JAK-STAT pathway has been associated with many types of disease, including a group of rare blood cancers called myeloproliferative neoplasms (MPNs), as well also used for the treatment of Vitiligo. Ruxolitinib is currently under the clinical trial of Phase III. The purpose of this study is to evaluate the efficacy and safety of ruxolitinib cream in adolescent and adult participants with non-segmental vitiligo for whom total body involved vitiligo area (facial and nonfacial) does not exceed 10% body surface area (BSA).

Dermavant Sciences GmbH (Cerdulatinib 0.37% gel/DMVT-502)

Cerdulatinib is a dual inhibitor of the Janus kinase (JAK) and spleen tyrosine kinase (Syk) pathways, which Dermavant is evaluating as a differentiated topical treatment option for vitiligo and other inflammatory skin conditions such as atopic dermatitis. The Phase IIa study is a multi-center, randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, and systemic exposure of cerdulatinib gel 0.37%, dosed twice daily for six weeks versus vehicle in 30 adult patients aged 18-70 years diagnosed with vitiligo. The primary endpoints of the study are the safety and tolerability of topical administration of cerdulatinib gel 0.37% in adult subjects with vitiligo assessed by frequency, duration, and severity of adverse events (local and systemic), vital signs, laboratory values, and local tolerability scale (LTS) scores.

Aclaris Therapeutics, Inc. (ATI-50002/ATI-502)

ATI-502 (AA-201 Topical), is an investigational topical Janus Kinase (JAK) 1/3 inhibitor, developed by aclaris therapeutics used to treat Vitiligo. Currently, ATI-502 is evaluated under the clinical trial study of Phase II. This is a multicenter, open-label study designed to evaluate the safety, tolerability, and efficacy of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo. Subjects would be required to have a clinical diagnosis of non-segmental facial vitiligo affecting at least 0.25% of total body surface area (TBSA) (excluding upper and lower eyelids, mucosal lip areas, and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Twenty-four eligible subjects would receive ATI-50002 Topical Solution, 0.46%, BID for 24 weeks.

Pfizer (PF-06651600)

PF-06651600 is an oral JAK3 inhibitor used to treat Vitiligo. The JAK pathways are believed to play an important role in inflammatory processes as they are involved in signaling for over 50 cytokines and growth factors, many of which drive immune-mediated conditions. JAK inhibition may offer patients with these conditions a potential new advanced treatment option. PF-06651600 initiated a Phase II clinical trial study. This is a randomized, double-blind, parallel-group, multicenter study with an extension period. The study would have a maximum duration of approximately 60 weeks. This includes an up to 4 weeks Screening Period, a 24-week dose-ranging period, an up to 24 week extension period and an 8 week Follow up Period.

Amgen (AMG 714)

AMG 714 (PRV-015) is a human immunoglobulin monoclonal antibody that binds to IL-15 developed by amgen used to treat Vitiligo. Currently, AMG 714 is evaluated under a clinical trial study. The Phase IIa, double-blind, placebo-controlled, multi-center, proof of concept trial of AMG 714 for the treatment of vitiligo. Participants would be randomized 2:1 to receive AMG 714 or placebo for AMG714. The random assignment would be stratified by active versus stable vitiligo.

Vitiligo Emerging Pipeline Landscape

Company Name	Product Name	Mechanism of Action	Route of Administration	Stage of Development
Incyte Corporation	Ruxolitinib/INCB018424	JAK1/JAK2 Inhibitors	Topical	Phase III
Dermavant Sciences GmbH	Cerdulatinib 0.37% gel/DMVT-502	JAK/Syk Inhibitors	Topical	Phase II
Aclaris Therapeutics, Inc.	ATI-50002	Janus kinase 1 Inhibitors; Janus kinase 3 Inhibitors	Topical	Phase II
Pfizer	PF-06651600	JAK3 Inhibitors	Oral	Phase II
Amgen	AMG 714	Interleukin 15 Inhibitors	Subcutaneous	Phase II

Autism Spectrum Disorder (ASD): Emerging Therapies

Vitiligo Emerging Therapies