FDA Approved Drugs: May & June, 2022

Amvuttra (Alnylam Pharma)

Vutrisiran, to be marketed under the brand name Amvuttra, has won an FDA approval to treat hereditary transthyretin amyloidosis (hATTR) polyneuropathy in adults. In the phase III HELIOS-A study, Amvuttra helped ATTR polyneuropathy patients achieve an average 2.2-point improvement on a modified neuropathy impairment score after nine months; half of the patients experienced some level of improvement. In the same study, Onpattro takers got 1.4 points better. By comparison, patients who took placebo in a historical Onpattro clinical trial called APOLLO experienced disease worsening of an average 17 points.

Voquezna (Phathom)

VoqueznaTriple Pak(vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak(vonoprazan, amoxicillin) is approved for the treatment of Helicobacter pylori (H. pylori) infection in adults.

The approval was based on data from a randomized, controlled, double-blind triple therapy/open-label dual therapy, phase III study HP-301, which compared the efficacy and safety of Voquezna Triple and Dual Pak with lansoprazole in combination with amoxicillin and clarithromycin in 1046 adults with H. pylori infection.

Mounjaro (Lilly)

Mounjaro is an injectable prescription medicine that is used along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes mellitus. Mounjaro is not for use in people with type 1 diabetes. It is not known if Mounjaro is safe and effective for use in children under 18 years of age. Mounjaro is a dual GLP-1 and GIP agonist and has demonstrated superior efficacy compared to other diabetes medications.The approval of Mounjaro was based on results from the phase III SURPASS program, which compared it to competitors such as injectable semaglutide, insulin glargine, and insulin degludec.

Vtama (Dermavant)

Vtama(tapinarof) Cream, 1% is an aryl hydrocarbon receptor agonist indicated for the topical treatment of plaque psoriasis in adults.

The approval was based on data obtained from 2 identical phase III trials that assessed the safety and efficacy of Vtama in 1025 adults (18 to 75 years of age) diagnosed with plaque psoriasis.

The primary endpoint for both studies was the hope that patients would earn a Physician Global Assessment (PGA) score of clear (0) or almost clear (1). Results from both trials showed that 36% and 40% of patients met the primary endpoint, respectively. Following 12 weeks of treatment, 73 Vtama patients achieved complete disease clearance (PGA 0).

FDA Approved Drugs: March & April, 2022

Vivjoa (Oteseconazole)

Vivjoa, the first FDA-approved product for Mycovia, is an azole antifungal indicated to reduce the incidence of recurrent vulvovaginal candidiasis (RVVC) in females with a history of RVVC who are NOT of reproductive potential. Oteseconazole received FDA Qualified Infectious Disease Product and Fast-Track designations to become the first FDA-approved therapy for RVVC. In 2019, Mycovia licensed oteseconazole to Jiangsu Hengrui Pharmaceuticals Co., Ltd., to develop and commercialize oteseconazole in China, including mainland China, Hong Kong, Macau and Taiwan, and Gedeon Richter Plc., a Hungary-based pharmaceutical company, to commercialize and manufacture oteseconazole in Europe, Russia, the Commonwealth of Independent States, Latin America and Australia. Mycovia also recognizes a tremendous potential for its oral fungal inhibitors and a growing need to treat a range of multi-drug resistant fungal pathogens.

Camzyos (Mavacamten)

Camzyosis the FIRST AND ONLY cardiac myosin inhibitor approved by the FDA indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms. Camzyos is an allosteric and reversible inhibitor selective for cardiac myosin. Camzyos modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. Camzyos shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with Camzyos reduces dynamic LVOT obstruction and improves cardiac filling pressures.

Ztalmy (Ganaxolone)

Ztalmy, a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor, is taken three times daily. Ztalmy is the FIRST ANDONLY FDA-approved treatment indicated specifically for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD) in patients two years of age and older.

PLUVICTO™ (Lutetium Lu 177 vipivotide tetraxetan)

Pluvictois a PSMA targeted radioligand therapy that delivers DNA-breaking radiation directly to the PSMA positive bone, nodal and visceral metastases. It is the FIRST AND ONLY PSMA-targeted radioligand therapy for men with PSMA+ mCRPC who have been treated with androgen receptor pathway inhibitors and a taxane-based chemotherapy.

Therapeutic Approaches for Targeting T Regulatory Cells in Autoimmunity

Regulatory T cells (Tregs) are a specialized CD4+ subpopulation of lymphocytes with regulatory functions that suppress excessive and uncontrolled immune responses, which inhibit adaptive and innate immune cells such as conventional T cells, B cells, antigen-presenting cells (APCs), natural killer (NK) cells, and so forth.

The most specific marker for these cells is FoxP3, which is localized intracellularly. Selected surface markers such as CD25high (high molecular density) and CD127low (low molecular density) could serve as surrogate markers to detect Tregs in routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease.

Regulatory T (Treg) cells maintain immune homeostasis by inhibiting abnormal/overactive immune responses to both autogenic and nonautogenic antigens. Treg cells play an important role in immune tolerance, autoimmune diseases, infectious diseases, organ transplantation, and tumor diseases.

  • Organ transplantation is the gold standard therapy for end-stage organ failure. Although, the results of organ transplantation have been ameliorated in recent decades, chronic rejection and the side effects of immunosuppressants are still an ongoing serious issue. None of the present immunosuppressive medications (in contrast to Tregs) have the potential to specifically suppress immune mechanisms. Various strategies are currently underway to avoid or minimize the use of immunosuppressive drugs. In this case, it may be possible that Tregs represent a promising solution to induce transplantation tolerance and control the immune response.
  • Autoimmune diseases as lifelong disorders are one of the major causes of mortality. The main etiology of autoimmune diseases is not fully understood; however, failure of immunological tolerance is a common cause of each autoimmune condition.
    • Regulatory T (Treg) cells, possess a strategic role in the maintenance of immune homeostasis, and their function has been closely linked to the development of diverse pathologies including autoimmunity and cancer. Consistently recent studies have highlighted that Treg dysfunction is a common denominator in autoimmunity, with reduced Treg cell frequencies and impaired suppressive function identified in a wide range of autoimmune diseases, including multiple sclerosis, SLE, type 1 diabetes, thyroiditis, and inflammatory bowel disease. Thus, it is becoming apparent that Treg cells possess a unique power in supervising autoimmune reactions and the re-establishment of self-tolerance.
  • Two main strategies have been developed to augment the numbers and/or increase the functional activity of Tregs. In vivo Treg therapies focus on the administration of immunomodulatory agents that enhance the number and/or function of Treg cells in vivo, and the adoptive Treg therapies transfer in vitro expanded Treg cells. Interventions that increase polyclonal endogenous Treg cells in vivo involve low-dose interleukin-2 (IL-2), mutant IL-2, IL2/Anti-IL-2 Ab complexes. In contrast, applications of antigen-based treatments could lead to the enhancement of antigen-specific Treg subsets. On the other hand, adoptive Treg cell therapies rely on the optimal isolation and expansion of Treg cells in vitro. Thus far, clinical trials in autoimmunity have only utilized expanded polyclonal Treg cell populations. However, antigen-specific Treg cells can be generated in vitro by genetic insertion of synthetic receptors (including engineered T cell receptors (TCR), chimeric antigen receptors (CAR) or B cell antibody receptors (BAR)), or by transformation of antigen-specific effector T (Teff) cells into induced Treg (iTreg) cells via stimulation in the presence of transforming growth factor beta (TGF-ß) and IL-2, transgenic FOXP3 overexpression, blockade of cyclin-dependent kinase 8 (CDK8) and CDK19 signaling, or a combination of cytotoxic T lymphocyte antigen 4 (CTLA-4) overexpression, IL-2 ablation and antigenic stimulation.
  • Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, autoimmune disorders, and to prevent allograft rejection. Multiple approaches such as adoptive Treg cell therapies as well as targeting mediators that can enhance the action of endogenous Treg cells are under evaluation, both in academia and industry.

FDA Approved Drugs: November, 2021

Voxzogo (BioMarin Pharmaceutical)

BioMarin Pharmaceutical’s Voxzogo (vosoritide) is the first FDA approved therapy for children with achondroplasia, an inherited disorder that causes the most common form of dwarfism. With this approval, the FDA also issued a Rare Paediatric Disease Priority Review Voucher (PRV), which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. Voxzogo, a C-type natriuretic peptide (CNP) analog, represents a new class of therapy, which acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.

Livtencity (Takeda)

Takeda’s Livtencity (maribavir) is the first and only treatment for adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet. This new molecular entity targets CMV at UL97, resulting in inhibition of viral DNA replication, encapsidation, and nuclear egress. It became available for prescription on December 2, 2021.

Cytalux (On Target Laboratories)

On Target Laboratories’s Cytalux (pafolacianine) is the first targeted fluorescent imaging agent indicated as an adjunct for the intraoperative identification of malignant lesions in patients with ovarian cancer. Cytalux, administered by standard IV in as little as one hour before surgery, binds to folate receptors that are overexpressed in most epithelial ovarian cancers and illuminate intraoperatively under near-infrared light.

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FDA Approved Drugs: April, 2021

Qelbree (viloxazine extended-release capsules): Supernus Pharmaceuticals, Inc.

FDA approved Qelbree (viloxazine extended-release capsules) for the treatment of attention-deficit hyperactivity disorder (ADHD) in pediatric patients 6 to 17 years of age. Qelbree represents the first novel non-stimulant treatment for ADHD. Supernus Pharmaceuticalsplans to make Qelbree available in the United States in Q2 2021.

Attention deficit hyperactivity disorder (ADHD) is a mental health disorder that can cause above-normal levels of hyperactive and impulsive behaviors. People with ADHD may also have trouble focusing their attention on a single task or sitting still for long periods of time.

The approval of Qelbree is based on the data from an extensive development program consisting of four Phase III clinical trials that studied more than 1000 pediatric patients from the age of 6 to 17 years. In December 2020, the Company announced positive results from a Phase III trial in adult patients with ADHD and plans to submit a supplemental New Drug Application to the FDA for Qelbree in adults in the second half of 2021.

Nextstellis (Drospirenone and Estetrol Tablets): Mayne Pharma

FDA approved Nextstellis (also trade name: Estelle), (3 mg drospirenone [DRSP] and 14.2 mg estetrol [E4] tablets), for the prevention of pregnancy. Nextstellis is the first and only contraceptive pill containing E4, a naturally produced estrogen during pregnancy, which can now be made from a plant source. Mayne Pharma anticipates the commercial launch of Nextstellisby at the end of June 2021.

Nearly 10 million American women use short-acting combination contraceptives (estrogen and progestin). Of these contraceptives, more than 99% contain ethinylestradiol (EE), a synthetic estrogen that binds widely to all estrogen receptors in the body.

The approval is based on the two-phase III clinical studies conducted in 3,725 women, Nextstelliswas shown both safe and effective and met its primary efficacy endpoint of pregnancy prevention while also meeting a variety of secondary endpoints that demonstrated favorable cycle control, bleeding control, safety, and tolerability.

Nextstellis was developed by a Belgian biotech company Mithra Pharmaceuticals. Mithra has signed 10 licensing deals for Estelle with a number of leading women’s health companies covering United States, Europe, Japan, South Korea, ASEAN, Russia, Brazil, Canada, Middle East, North Africa, Southern Africa and Australia. Mayne Pharma has a 20-year exclusive license and supply agreement in the United States and Australia for Nextstellis.

  • In May 2020, Mithra has entered into an exclusive 20-year license and supply agreement with Mayne Pharma for the commercialization of its combined oral contraceptive E4/DRSP (Estelle) in Australia.
  • In October 2019, Mithrahas signed a License and Supply Agreement (LSA) with Mayne Pharma Group for an exclusive license to commercialize Estelle in the US.

As a result of receiving FDA approval for Nextstellis, Mayne Pharma will pay Mithra US$11m in cash and issue 85.8m ordinary Mayne Pharma shares.

World Asthma Day 2021

World Asthma Day is observed every year on the first Tuesday of May to raise awareness about Asthma and improves the lives of all people with Asthma. Asthma is an inflammatory disorder of the airways causing symptoms such as cough, wheezing, chest tightness and shortness of breath.

This year’s World Asthma Day theme is “Uncovering Asthma Misconceptions”. The theme provides a call to action to address common widely held myths and misconceptions concerning asthma that prevent persons with asthma from enjoying optimal benefit from the major advances in the management of this condition. Common misconceptions surrounding asthma include:

Myth #1

Asthma is a childhood disease; individuals will grow out of it as they age.

Fact: No, asthma can develop at any age in children, adolescents, and the elderly.

Myth #2

Asthma is infectious.

Fact: Asthma is not infectious. However, Acute attack gets precipitated on exposure to various allergens or due to infections (mostly viral).

Myth #3

Asthma sufferers should not exercise.

Fact: When asthma is well controlled, asthma subjects are able to exercise and even perform top sport.

Myth #4

Asthma is only controllable with high dose steroids.

Fact: Asthma is most often controllable with low dose inhaled steroids.

COVID-19 has brought suffering to people everywhere. But patients with asthma are more affected during COVID. In the era of COVID-19 pandemic, here are few measures for Asthma patients:

Steps to protect yourself from COVID-19

  • Get a COVID-19 vaccine shot when it is available.
  • Wear a mask that properly covers your nose and mouth.
  • Maintain social distancing and stay at least 6 feet distance while at public places.
  • Wash your hands with soap and water or use hand sanitizer with 60% alcohol several times in a day
  • Avoid all non-essential travel
  • If anyone in your home is sick, home quarantine the person to reduce the risk of spreading the virus.

Tips to Manage Asthma

  • Stay away from your asthma triggers.
  • Continue having your regular asthma medications including inhalers with steroids
  • Never discontinue any medications or change asthma treatment plant without talking to your physician
  • Stock at home your emergency supply of prescription medications such as inhalers and other drugs. Make sure you also maintain a stock of non-prescription medications and essentials on hand.
  • Be very cautious while using any cleaning agents and disinfectants.

Coronavirus (COVID19): Updates

Glenmark Pharmaceuticals had launched FabiFlu, India’s first COVID-19 drug

Glenmark Pharmaceuticals had launched FabiFlu, an antiviral drug Favipiravir, to cure patients with mild to moderate coronavirus at a price tag of about Rs 103 per tablet. FabiFlu would be available in the form of a 200 mg tablet and will be at a maximum retail price (MRP) of Rs 3,500 for a strip of 34 tablets. It is the first oral favipiravir-approved medication for the treatment of COVID-19 in India. FabiFlu is a prescription-based medication with a recommended dose being at 1,800 mg twice daily on day one, followed by 800 mg twice daily up till day 14.

Cipla had launched Cipremi, a COVID-19 Antiviral Drug

Cipla had launched antiviral drug i.e., Cipremi for the treatment of COVID-19. Cipremi is available in the form of lyophilized powder (freeze dry) for injection 100mg. It has been approved for adult and pediatric patients who have been hospitalized. This drug has been granted regulatory approval by the Drug Controller General of India (DCGI) for restricted emergency use in India as part of the accelerated approval process considering the urgent and unmet medical need. The clinical trials have demonstrated the efficacy of Cipremi for the patients on oxygen support after falling ill to coronavirus. 

United States provided $2 Billion to Novavax & Regeneron for Covid-19 Vaccine

The federal government awarded $2 billion to Novavax Inc. & Regeneron Pharmaceuticals for the development and manufacturing of an experimental drug and a potential vaccine against Covid-19. Novavax Inc. has received $1.6 billion from the federal government’ to fund clinical studies of its experimental coronavirus vaccine and establish large-scale manufacturing of doses. Regeneron Pharmaceuticals Inc. has received a $450 million federal contract to manufacture thousands of doses of its experimental Covid-19 treatment that the government would distribute for free to the public if the drug is authorized for use by regulators.

BioSig Technologies Collaborates with Albany Molecular for its Drug Merimepodib, a Coronavirus Treatment

BioSig Technologies had entered into the collaboration with Albany Molecular Research Inc to evaluate the merimepodib for the treatment of SARS-CoV-2, the virus that causes Covid-19. Under the terms of the collaboration, both companies would evaluate the drug as a standalone treatment and in combination with other antiviral agents or immune modulators. This collaboration would help in rapid transfer, scale-up and validation of merimepodib API manufacture as the future supply chain and commercialization strategy.

Hetero Receive the Approval to Produce & Market Remdesivir

Indian pharmaceutical firm Hetero had received approval from the Drug Controller General of India to manufacture and market the experimental antiviral drug remdesivir for the treatment of coronavirus. Hetero’s generic version of Remdesivir would be sold under the brand name Covifor in India. Covifor would be available in 100 mg vials that would be injected into the patient at a hospital facility under the proper supervision of a doctor or trained healthcare worker. The drug would be launched in India under a licensing agreement with Gilead Sciences Inc, an American biopharmaceutical firm, to expand access to Covid-19 medication in poor countries.

Mateon Therapeutics Secured a $2 Million Financing with Golden Mountain Partners (GMP) to Conduct Clinical Trial Evaluating OT-101 against COVID-19

Mateon Therapeutics had secured a $2 million in debt financing with Golden Mountain Partners (GMP) for the conduct of a clinical trial evaluating OT-101 against COVID-19. OT-101 is an antisense against the host TGF-β protein required for viral replication and its overexpression likely to cause the wide range of clinical symptoms associated with COVID-19 including Kawasaki syndrome.

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

Sickle Cell Disease Emerging Pipeline

Sickle Cell Disease (SCD) is a genetic disease that is a form of inherited anemia arising from problems with the structure and function of red blood cells. It is an inherited disease caused by a defect, a single mutation, in the beta-globin gene that helps make adult hemoglobin. Abnormal hemoglobin, called hemoglobin S, causes sickle cell disease. The signs and symptoms of sickle cell disease include swelling of the hands and feet, anemia, fatigue, extreme tiredness, jaundice, and skin discoloration. Sickle cell disease can lead to complications such as infections, delayed growth, and episodes of pain, acute chest syndrome, and stroke. According to the Centres for Disease Control and Prevention (CDC), approximately 100,000 Americans are affected by sickle cell disease. Sickle Cell Disease occurs among about 1 out of every 365 Black or African-American births. About 1 in 13 Black or African-American babies is born with sickle cell trait (SCT).

Several pharmaceutical companies such as AstraZeneca, Global Blood Therapeutics, Bluebird bio, Micelle BioPharma Inc, Novartis Pharmaceuticals, Cyclerion Therapeutics, and Imara, Inc. are developing the drugs for the treatment of sickle cell disease.

Global Blood Therapeutics (Voxelotor)

Voxelotor is an oral therapy taken once daily that directly inhibits sickle hemoglobin polymerization, which causes red blood cells (RBCs) to deform and become sickle-shaped. Voxelotor acts by binding to hemoglobin and stabilizing RBCs in an oxygenated state. This increases hemoglobin’s affinity for oxygen and inhibits polymerization and the resultant sickling and destruction of RBCs. The potential of Voxelotor to slow the progression of sickle cell disease and its devasting downstream effects across a wide range of studies, including the HOPE-KIDS 2 post-approval confirmatory study using transcranial doppler (TCD) flow velocity to evaluate the reduction in stroke risk in children 2 to 15 years of age. Voxelotor was granted Breakthrough Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Sickle cell disease, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA). The European Commission (EC) has designated Voxelotor as an orphan medicinal product for the treatment of patients with Sickle cell disease.

Bluebird bio (LentiGlobin /BB305/ HGB-210)

LentiGlobin BB305 drug is being developed for the treatment of beta-thalassemia major and severe sickle cell disease by inserting a fully functional human beta-globin gene into the patient’s own hematopoietic stem cells ex-vivo and then transplanting those modified cells into the patient through infusion, also known as autologous stem cell transplantation.

Micelle BioPharma Inc (SC411/ Docosahexaenoic Acid/ Altemia)

SC411(Altemia) is the proprietary product candidate that is being developed for the treatment of Sickle Cell Disease. Altemia consists of a complex proprietary mixture of various fatty acids, primarily in the form of Ethyl Cervonate (Micelle’s proprietary blend of docosahexaenoic acid and other omega-3 fatty acids), and surface-active agents formulated using ALT specifically to address the treatment of SCD. The drug is encapsulated in a soft gelatin capsule for oral administration. Altemia is well-positioned to deliver a narrow, therapeutic dose of certain lipids directly to the membrane of red blood cells of sickle cell patients. The combination of ALT drug delivery technology and highly purified lipids may reduce VOC significantly. It has the potential to address the inflammatory symptoms of SCD and to assist in reducing sickle cell events in general. Altemia is effective in reducing the sickle cell crisis events and related mortality. The double-blind, randomized, multicenter phase II study of SC411 (Altemia) in children with sickle cell disease (SCOT Trial). The SCOT trial investigated the effect of three different doses of SC411 on selected clinical and biochemical endpoints in 67 children with SCD aged 5-17 years old. 

Novartis Pharmaceuticals (Crizanlizumab)

Crizanlizumab (SEG101) is an investigational humanized monoclonal antibody blocking P-selectin mediated multicellular adhesion that is in late-stage development for the prevention of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD). Crizanlizumab acts by binding to the molecule called P-selectin on the surface of platelets and endothelium in the blood vessels. It inhibits the interactions between endothelial cells, platelets, red blood cells, sickled red blood cells, and leukocytes.

Cyclerion Therapeutics (IW-1701/ Olinciguat)

Olinciguat is an orally administered, once-daily, vascular sGC stimulator designed for the treatment of sickle cell disease (SCD). Olinciguat has the potential to manifest various properties such as to improve local blood flow to organs, reduce vascular inflammation, and reduce the proportion of sickled cells. Olinciguat has been granted Orphan Drug Designation for Sickle Cell Disease by the U.S. Food and Drug Administration. It is currently in a Phase II study in patients with SCD, the STRONG-SCD study.

Imara, Inc. (IMR-687)

IMR-687 is an oral, once-a-day, potentially disease-modifying treatment for sickle cell disease (SCD) and β-thalassemia. IMR-687 is a highly selective, potent small-molecule inhibitor of PDE9. It acts primarily on red blood cells (RBCs). It has the potential to act on white blood cells (WBCs), adhesion mediators, and other cell types that are implicated in sickle cell disease.

Modus Therapeutics AB (Sevuparin)

Sevuparin is an innovative, proprietary polysaccharide drug with anti-adhesive, anti-aggregate, and anti-inflammatory effects due to its multimodal mechanism of action. The drug candidate has the potential to restore blood flow and prevent further microvascular obstructions in a number of diseases. Modus has completed a global Phase II study of sevuparin in hospitalized sickle cell disease (SCD) patients. The randomized, double-blinded study included 144 SCD-patients at clinical sites across Europe, the Middle East, and the Caribbean. The study compared intravenously (IV) administered sevuparin with a placebo in patients admitted to the hospital with an acute vaso-occlusive crisis (VOC) associated with SCD. The study also assessed several pain-related secondary endpoints.

Emerging Pipeline Landscape: Sickle Cell Disease

Company NameProduct NameMechanism Of ActionRoute Of AdministrationStage Of Development
Global Blood TherapeuticsVoxelotorInhibits sickle hemoglobin polymerizationOralPhase III
Bluebird bioLentiGlobin BB305Gene TransferenceIntravenousPhase II/III
Bluebird bioBCL11A shRNA (mir)RNA Interference to stimulate the gene expressionIntravenousPhase I
Micelle BioPharma IncSC411/ Docosahexaenoic AcidLipid ReplenishmentOralPhase II
Novartis PharmaceuticalsCrizanlizumab (SEG101)P-Selectin InhibitorIntravenousPhase III
Cyclerion TherapeuticsIW-1701/ OlinciguatSoluble Guanylyl Cyclase AgonistsOralPhase II
Imara, Inc.IMR-687PDE9 InhibitorOralPhase II
Modus Therapeutics ABSevuparinCell Adhesion Molecule InhibitorsIntravenousPhase II