Autism Spectrum Disorder (ASD): Emerging Therapies

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 NameProduct NameStage of DevelopmentMechanism of ActionRoute of Administration
Otsuka Pharmaceutical Brexpiprazole/OPC-34712/ LuAF41156  Phase IIIDopamine D2 Receptor Partial agonists; Serotonin 1A Receptor Partial AgonistsOral
NobelpharmaNPC-15 GranulesPhase II/III_oral
GW Research LtdGWP42006/ CBDV  Phase IICannabinoid Receptor ModulatorsOral
Hoffmann-La RocheBalovaptan/RO5285119/RO7017773Phase IIIAntagonist of the V1A Vasopressin ReceptorOral
Hoffmann-La RocheRG7816Phase I_
AllerganCariprazinePhase ICYP3A4 InhibitorOral
CuremarkCM-ATPhase IIIEnzyme ModulatorsOral

Vitiligo Emerging Therapies

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 NameProduct NameMechanism of ActionRoute of AdministrationStage of Development
Incyte CorporationRuxolitinib/INCB018424JAK1/JAK2 InhibitorsTopicalPhase III
Dermavant Sciences GmbHCerdulatinib 0.37% gel/DMVT-502JAK/Syk InhibitorsTopicalPhase II
Aclaris Therapeutics, Inc.ATI-50002Janus kinase 1 Inhibitors; Janus kinase 3 InhibitorsTopicalPhase II
PfizerPF-06651600JAK3 InhibitorsOralPhase II
AmgenAMG 714Interleukin 15 InhibitorsSubcutaneousPhase II

Cystic Fibrosis: Emerging Pipeline Landscape

Cystic Fibrosis is an autosomal, recessive inheritable genetic disease that causes severe damage to the respiratory and digestive systems. This damage often results from a buildup of thick, sticky mucus in the organs. It occurs as a result of a defect in what’s called the “cystic fibrosis transmembrane conductance regulator” gene, or CFTR gene. This gene controls the movement of water and salt in and out of your body’s cells. A sudden mutation causes the abnormality in CFTR gene and commonly affected the various organs including the lungs, pancreas, liver, and intestines. The symptoms of cystic fibrosis can vary depending on the person and the severity of the condition. The age at which symptoms develop can also differ. Symptoms may appear at infancy, but for other children, symptoms may not begin until after puberty or even later in life. As time passes, the symptoms associated with the disease may get better or worse.

Around 70,000-80,000 people worldwide are suffering from the Cystic Fibrosis. Cystic Fibrosis has the highest incidence and prevalence in Caucasian populations and is less common in other population groups. Every year, around 1,000 people are diagnosed with Cystic Fibrosis in the United States.

Several pharmaceutical companies are developing the novel drugs for the treatment of Cystic Fibrosis. The pipeline landscape of the cystic fibrosis is robust with the involvement of several drugs such as vancomycin hydrochloride inhalation powder, OligoG, ELX-02 and VX-561 etc. 

The pharmaceutical companies involved in developing emerging drugs against Cystic Fibrosis are as follows:

Savara Pharmaceuticals (AeroVanc)

AeroVanc (vancomycin hydrochloride inhalation powder) is an inhaled dry powder form of vancomycin for the treatment of the persistent (MRSA) lung infection in people living with Cystic Fibrosis. AeroVanc is in Phase III stage of development for the treatment of the Methicillin-resistant Staphylococcus aureus (MRSA) lung infection in Cystic Fibrosis. AeroVanc is effective in improving the clinical efficacy, and reducing the adverse effects due to lessor systemic drug exposure in comparison to the intravenous antibiotic treatment.

AlgiPharma (OligoG)

OligoG is a dry powder drug that has been shown to decrease the thickness of mucus in the lungs and may help individuals with cystic fibrosis clear mucus easier. OligoG help in improving the effectiveness of some antibiotics. It is administered using a dry powder inhaler and also developed as a liquid for use with a nebulizer

Currently, Phase IIb trial is currently running in Australia, with another Phase 2b scheduled to start in Europe H1 2020. The drug candidate OligoG for Cystic Fibrosis has Orphan Drug designation from both the European Medicines Agency and the FDA

Eloxx Pharmaceuticals, Inc. (ELX-02)

ELX-02, is a small molecule drug candidate designed to restore production of full-length functional proteins. It is in the early stages of clinical development focusing on cystic fibrosis and nephropathic cystinosis. ELX-02 is an investigational drug that has not been approved by any global regulatory body.

Furthermore, ELX-02, is a eukaryotic ribosomal selective glycoside (ERSG) designed to increase the read-through activity in patients with nonsense mutations and enable the production of sufficient amounts of full-length functional protein to restore activity.

Its Phase II program has been given a score of “high priority” by the European Cystic Fibrosis Society-Clinical Trial Network (ECFS-CTN).

Laurent Pharmaceuticals Inc. (LAU-7b)

LAU-7b is a novel and improved solid dosage form of fenretinide, requiring. once-a-day oral administration. It was recently tested in adult patients with Cystic Fibrosis in a dose-ascending where Phase Ib study, showing a good safety and tolerability, and promising pharmacokinetic and pharmacodynamic results.

The company is currently recruiting patients for its Phase II safety and efficacy study in adult patients with Cystic Fibrosis. The goal of the Phase II trial is to evaluate LAU-7b’s effect on the preservation of lung function, by reducing persistent unresolved inflammation in the lung and stimulating its return to homeostasis. The study would enroll 136 adults with Cystic Fibrosis for a treatment duration of 6 months and will involve more than 30 clinical sites in the USA and Canada.

Corbus Pharmaceuticals Inc. (Lenabasum)

Lenabasum is a rationally-designed, oral, small-molecule that selectively binds as an agonist to the cannabinoid receptor type 2 (CB2). It has a direct effect on fibroblasts to limit the production of fibrogenic growth factors and extracellular connective tissue that lead to tissue fibrosis. Lenabasum treatment has resulted in lowering the and longer time to pulmonary exacerbations in Phase II cystic fibrosis study. The Lenabasum had demonstrated the safety and tolerability profile in clinical studies. It has demonstrated safety and tolerability profile in clinical studies

Vertex Pharmaceuticals Incorporated (VX-561)

VX-561 is a deuterated form of ivacaftor that replaces one or more hydrogen atoms with deuterium. It is designed to keep CFTR proteins at the cell surface open longer to improve the flow of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

Vertex Pharmaceuticals Incorporated (VX-121 + TEZACAFTOR + VX-561)

VX-121 and tezacaftor act by increasing the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the CFTR protein. VX-561 (deuterated ivacaftor) is designed to keep CFTR proteins at the cell surface open longer to improve the flow of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways.

SolAeroMed Inc (S-1226)

S-1226 is a novel fast-acting bronchodilator, with airway lubricant properties to remove mucus.  It acts as a cough suppressant and is an anti-inflammatory agent. S-1226 is based on amalgation of Perflubron (a synthetic surfactant derivative) and carbon dioxide. When combined in inhalation therapy as S-1226 delivered by nebulization these compounds offer significant promise to treat respiratory diseases where breathing is compromised due to bronchoconstriction, excess mucus production, and/or impaired mucus motility. It has demonstrated the safety and efficacy for the treatment of Cystic Fibrosis.

Cystic Fibrosis Emerging Pipeline Landscape

Company NameProduct nameStage of developmentMechanism of ActionRoute of administration
Savara Inc.Vancomycin inhalation powderPhase IIICell wall inhibitorsInhalation
AlgiPharma ASOligoG DPIPhase IIBacterial growth inhibitorsInhalation
Eloxx Pharmaceuticals, Inc.ELX-02Phase IIRibosomal protein modulatorsSubcutaneous
Corbus Pharmaceuticals Inc.LenabasumPhase IICannabinoid receptor CB2 agonistsOral
Laurent Pharmaceuticals Inc.LAU-7bPhase IIRetinoic acid receptor agonistsOral
Vertex Pharmaceuticals IncorporatedVX-121 + TEZACAFTOR + VX-561 Phase IIRegulated CFTR geneOral
SolAeroMed Inc.S-1226Phase IICell membrane permeability enhancers    Inhalation
Vertex Pharmaceuticals Incorporated VX-561Phase IIRegulated CFTR geneOral