Multiple Sclerosis, Alzheimers disease, and Migraine

Part
01
of three
Part
01

Drugs in Development: Multiple Sclerosis

A few of the drugs that are in development for multiple sclerosis in the US include tcelna, ATA188 & ATA190, NurOwn, Diroximel, Ozanimod, Ublituximab, MN-166, and CHS-131. Details on the manufacturers of these drugs and other multiple sclerosis drugs by these manufacturers have been outlined below.

Tcelna by Opexa TheraPeutics

  • Tcelna is a T-cell immunotherapy that is under development for treating Secondary Progressive Multiple Sclerosis.
  • Five clinical trials have been completed by the manufacturer of Tcelna, Opexa Therapeutics, for the effectiveness of the drug,
  • The US FDA granted tcelna a Fast Track status due to its promising potential.
  • Opexa Therapeutics does not have any fully developed multiple sclerosis drug on the market.

ATA188 and ATA190 by Atara Biotherapeutics

  • Atara Biotherapeutics is developing allogeneic ATA188 and autologous ATA190 with its "complementary T-cell immunotherapy technology." Both drugs could potentially slow down or halt the development of multiple sclerosis.
  • A phase 1 clinical trial testing the safety of ATA188 and ATA190 in patients with progressive multiple sclerosis began in 2017 and is expected to be completed by October 2021.
  • Atara Biotherapeutics does not have any fully developed multiple sclerosis drug on the market.

NurOwn by Brainstorm Cell Therapeutics

  • NurOwn is an amyotrophic lateral sclerosis therapy in its phase 3 development stage for patients with multiple sclerosis.
  • NurOwn is also known as autologous MSC-NTF It is being developed by BrainStorm Cell Therapeutics.
  • BrainStorm Cell Therapeutics does not have any fully developed multiple sclerosis drug on the market.

Diroximel Fumarate by Biogen

  • Also known as Vumerity, diroximel fumarate is an investigational drug that reduces disease activity in patients that have been newly diagnosed with multiple sclerosis.
  • A new drug application for diroximel fumarate was just accepted by the FDA in February 2019.
  • Vumerity was initially developed by Alkermes but in 2017, it was licensed to Biogen.
  • Natalizumab is a multiple sclerosis and Crohn's disease drug on the market that was developed by Biogen and Elan Pharmaceuticals. It is also known as TYSABRI.
  • Avonex (Interferon beta-1a) is a treatment by Biogen for relapsing multiple sclerosis.
  • Zinbryta (daclizumab) is a multiple sclerosis drug by Biogen and AbbVie. However, it was taken off the market in April 2018.

Ozanimod by Celgene Corporation

  • Ozanimod is an oral receptor modulator developed by Celgene Corporation for treating adults with relapsing multiple sclerosis.
  • In 2017, Celgene submitted a New Drug Application for ozanimod. This New Drug Application was rejected by the FDA "due to shortcomings in the preclinical and clinical pharmacology parts of its package."
  • Celgene Corporation announced in March 2019 that it submitted another New Drug Application to the FDA for the drug.
  • Celgene Corporation does not have any fully developed multiple sclerosis drug on the market.

Ublituximab (TG-1101) by TG Therapeutics

  • Ublituximab (TG-1101) is a "monoclonal antibody [by TG Therapeutics] that targets a unique epitope on the B-lymphocyte CD20 antigen."
  • Although it was developed to treat B-cell proliferative disorders, it has anti-CD20 antibodies which are effective in treating multiple sclerosis.
  • Ublituximab is in its phase 3 clinical trial stage. This study is focused on patients with multiple sclerosis and hematologic malignancies.
  • TG Therapeutics does not have any fully developed multiple sclerosis drug on the market.

MN-166 by MediciNova

  • MN-166 (ibudilast) by Medicinova is an investigational drug for the treatment of progressive multiple sclerosis, drug addiction, ALS, and pain.
  • In April 2019, Medicinova announced its commencement of a phase 2b and a phase 3 clinical trial of ibudilast in patients with amyotrophic lateral sclerosis (ALS).
  • Medicinova does not have any fully developed multiple sclerosis drug on the market.

CHS-131 by Coherus BioSciences

  • CHS-131 is a novel oral drug for multiple sclerosis patients.
  • A phase 2b clinical trial for the efficacy of CHS-131 in patients with multiple sclerosis was done over the course of six months in 2016.
  • Coherus Biosciences is still contemplating filing a New Drug Application with the FDA for CHS-131.
  • Coherus Biosciences does not have any fully developed multiple sclerosis drug on the market.

OTHER DRUGS IN THE PIPELINE FOR MULTIPLE SCLEROSIS

  • Ofatumumab (Arzerra) and Mayzent (siponimod) are multiple sclerosis drugs in development by Novartis AG. Mayzent was approved by the FDA in May 2019. Although Novartis AG is headquartered in Switzerland, it is a multinational company that has a large US market.
  • Afinitor (everolimus), Extavia (Interferon beta-l b), Gilenya (fingolimod), and Lescol (fluvastatin sodium) are drugs for multiple sclerosis that have already been developed and marketed by Novartis.

RESEARCH STRATEGY:

Our first approach for this request was to find any existing documents or lists of drugs that are in development for multiple sclerosis. We examined healthcare related websites such as Medscape and Pharmaceutical Journal. Websites like MS Trust and MS Discovery offered these lists. However, we found that these lists were outdated as most of the drugs have already been released and marketed. There were only one or two drugs still being developed but since these drugs were manufactured by pharmaceutical companies outside the US, we did not include them.

Next, we focused on the best-possible sources. We specifically looked for databases with drug pipeline data. Through an advanced search on BioPharm Catalyst, we were able to find some of the drugs in development for multiple sclerosis. To verify that we were on the right track, we also reviewed the most recent clinical trials for multiple sclerosis and checked to see what drugs were being used in these trials. We focused only on clinical trials that are still ongoing or about to begin. We excluded terminated clinical trials as this could mean the drug will not be developed anymore. Through both strategies, we were able to gather nine drugs by eight companies that are still in development for multiple sclerosis.

To find the drugs for multiple sclerosis that these companies currently have on the market, we relied on their respective websites for a list of drugs they developed. In order to confirm that we did not miss any drugs, we perused their annual reports within the past few years. We also leveraged databases like CenterWatch which provided lists of drugs manufactured by several US pharmaceutical companies. The aforementioned strategies did not help in finding any information on which of these drugs might do well financially. However, the multiple sclerosis drugs in pipeline by Novartis and Biogen have more media coverage than others.

Part
02
of three
Part
02

Drugs in Development: Alzheimer's disease

Five drugs being developed to cure Alzheimer are BAN2401, ALZ-801, PTI-125, J147, and NDX-1017. Companies that are developing them are M3 Biotechnology, Alzheon, Cassava Sciences, Eisai and Biogen, Five Eleven Pharma and Abrexa Pharmaceuticals.

New Drugs in development against Alzheimer

BAN2401
ALZ-801
  • ALZ-801 is a drug designed to treat Alzheimer that has entered phase 3 of the clinical trial phase.
  • ALZ-801 recorded positive results in phase 3.
  • A company called Alzheon is currently developing it.
  • The FDA has granted the drug the status of fast track.
  • It has the potential to be the first drug to succeed in treating Alzheimer.
PTI-125
J147
NDX-1017

Companies and their current drugs against Alzheimer's Disease

Eisai and Biogen
  • According to its website, Biogen has no actual treatment against Alzheimer.
  • Biogen has a pipeline of trials for drugs against Alzheimer's at different phases of trials such as Elenbecestat (E2609) which is in phase 3, BAN2401 in phase 2, BIIB092 (gosuranemab) in phase 2, BIIB076 (anti-tau mAb, and BIIB080 (IONIS-MAPTRx) which are both in phase 1 of clinical trials.
  • Eisai and Biogen have not yet succeeded in developing an Alzheimer drug, and they have canceled the trial of a drug called Aducanumab.
  • Aside from developing together BAN2401 and the failed Aducanumab, they are also developing Elenbecestat.
  • The success of BAN2401 is unsure, given bad financial results of the drug, but the company is hopeful it will be a success.
  • Alzheimer drugs are notoriously difficult to produce, with only four being developed between 1998 and 2017.
  • 146 trial drugs have been also been canceled between the given time period.
Alzheon
Cassava Sciences
Abrexa Pharmaceuticals
  • Abrexa is a company funded with $7 million, and the company has the aim of developing a treatment drug against Alzheimer's.
  • It was funded last 2011.
  • Abrexa is a small private company developing a new Alzheimer's drug, J147.
  • They have been working for a long time to raise enough funds to put their licensed drug to trial.

M3 Biotechnology

Drugs projected to do well financially


Part
03
of three
Part
03

Drugs in Development: Migraine

Some of the drugs that are in development for migraines include AMG 333, AXS-07, Lasmiditan, rimegepant, ALD1910, BHV3500, eptinezumab, BHV-3500, and Qtrypta.

AXS-07 by Axsome Therapeutics

  • AXS-07 is an oral drug for treating migraine. It is under development by Axsome Therapeutics.
  • AXS-07 consists of rizatriptan and MoSEIC meloxicam.
  • Axsome Therapeutics is currently working on the MOMENTUM trial for AXS-07. The clinical trial is expected to be completed by March 2020.
  • Axsome Therapeutics does not have any migraine drug on the market.

Lasmiditan by Eli Lilly

  • Eli Lilly submitted Lasmiditan for FDA approval in November 2018. It is an oral investigational drug for the treatment of migraine in adults.
  • A phase 3 clinical trial to study the effectiveness of lasmiditan over four migraine attacks is in works and will be completed by 2021.
  • Emgality (galcanezumab-gnlm) is the only FDA approved drug for migraine that is currently being marketed by Eli Lilly.
  • Galcanezumab was approved by the FDA in September 2018.

Eptinezumab and ALD1910 by Alder BioPharmaceuticals

  • Eptinezumab is an investigational antibody for migraine prevention.
  • Alder BioPharmaceuticals just completed a phase 3 study for the effectiveness of eptinezumab in chronic migraine. It is currently undergoing an open-label safety study.
  • ALD1910 is an antibody that is designed to prevent the proteins facilitating migraine.
  • ALD1910 is still in its preclinical stage. No clinical trials have been done for it yet as it is "undergoing Investigational New DrugIND)-enabling preclinical studies."
  • Alder BioPharmaceuticals does not have any migraine drug on the market yet.

BHV-3500 and Rimegepant by Biohaven Pharmaceuticals

  • BHV-3500 is a third generation small molecule antagonist for acute treatment of migraine.
  • The phase 2 and phase 3 clinical trials for the efficacy of BHV-3500 began March 2019.
  • BHV-3500 is not an oral drug. It requires intranasal administration.
  • Rimegepant is an oral potent drug for the prevention and treatment of migraine.
  • Rimegepant was licensed in 2016. Its phase 2 and phase 3 clinical trials began in November 2018 and are still ongoing.
  • Biohaven Pharmaceuticals does not have any migraine drug on the market yet.

Qtrypta by Zosano Pharma Corporation

  • ADAM Zolmitriptan Qtrypta (M207) is an investigational drug for the treatment of migraine.
  • Qtrypta can be administered both orally and nasally.
  • Qtrypta has only been evaluated in a phase 1 clinical study.
  • Zosano Pharma Corporation has not fully developed and released any migraine drug to the market.

Research Strategy:

Our first approach for this request was to find any existing documents or lists of drugs that are in development for migraines We examined healthcare related websites such as Medscape and Pharmaceutical Journal but these websites only had lists of drugs in development for more common diseases like diabetes. Next, we focused on the best-possible sources. Specifically, we looked for databases with drug pipeline information. Through an advanced search on BioPharm Catalyst, we were able to find some of the drugs in development for migraine. To verify that we were on the right track, we also reviewed the most recent clinical trials for migraine and checked to see what drugs were being used in these trials. We focused only on clinical trials that are still ongoing or about to begin. We excluded terminated clinical trials as this could be an indication that the drug will not be developed anymore. Through both strategies, we were able to gather seven drugs by five companies that are still in development for migraines. Of note, we excluded drugs by companies based outside the US such as ubrogepant and atogepant by Allergan.

To find the drugs for migraines that these companies have on the market, we relied on their respective websites for a list of drugs they developed. In order to confirm that we did not miss any drugs, we perused their annual reports within the past few years. We also leveraged databases like CenterWatch which provided lists of drugs manufactured by several US pharmaceutical companies.
Sources
Sources

From Part 01
From Part 02
Quotes
  • "Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") announced that a global Phase III clinical study (Clarity AD/Study 301) of BAN2401, an anti-amyloid beta protofibril antibody, in patients with early Alzheimer's disease has been initiated. "
  • "BAN2401 is being jointly developed by Eisai and Biogen Inc. (Headquarters: Cambridge, Massachusetts, United States, "Biogen")."
  • "Eisai aims to create innovative medicines for Alzheimer's disease as soon as possible in order to further contribute to addressing the unmet medical needs of, as well as potentially increasing the benefits provided to, patients and their families."
  • "In March 2014 Eisai and Biogen entered into a joint development and commercialization agreement for BAN2401 and the parties amended that agreement in October 2017. "
Quotes
  • "Initial Investigation of [18F]P16-129 in Alzheimer's Disease Patients and Healthy Volunteers"
  • "This study investigates the initial safety profile of [18F]P16-129 in healthy volunteers including dosimetry determination, and compares the uptake and kinetics of [18F]P16-129 with the FDA approved drug [18F]florbetapir in the brains of Alzheimer's disease patients."
  • "Study Phase ICMJE Phase 1"
Quotes
  • "ALZ-801, an oral pro-drug of tramiporsate, received Fast Track designation for development as a disease modifying treatment for AD. "
  • " In the North American Phase 3 trial, patients homozygous for apolipoprotein e4 allele (APOE4/4) showed meaningful benefits in Mild AD patients (Abushakra et al. 2016 & 2017). We analyzed individual responses and response rates on the clinical outcomes."
Quotes
  • "ALZ-801 – Phase 3-Ready Oral Small Molecule Program Designed to Inhibit Formation of Neurotoxic Soluble Amyloid Oligomers Represents Optimized and Differentiated Treatment Paradigm for Alzheimer’s Disease"
Quotes
  • "Cassava Sciences Completes Patient Enrollment for a Phase 2a Study in Patients with Alzheimer’s Disease"
  • "Cassava Sciences, Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company, announced the completion of patient enrollment in a clinical study evaluating the safety of its investigational drug, PTI-125, in patients with Alzheimer’s disease. "
  • "Cassava Sciences expects to announce results of its Phase2a study in the second half of 2019, after study participants complete drug treatment and their data are analyzed."
  • "The mission of Cassava Sciences is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Over the past ten years, we have combined state-of-the-art technology with new insights in neurobiology to develop novel solutions for Alzheimer’s disease. We own worldwide development and commercial rights to our research programs in Alzheimer’s disease, and related technology, without royalty obligations to any third-party."
Quotes
  • "Promising Alzheimer’s Drug, J147, Made From Curcumin Appears to Make Cells Younger"
  • "Scientists have finally cracked the code of how an experimental new drug called J147, which has a proven track record of reversing Alzheimer’s disease in mice, turns back the clock in cells, making them appear more youthful. The new discovery is a crucial step in readying the drug for human studies."
Quotes
  • "This Phase I clinical study is a randomized, double-blind, placebo-controlled, parallel-design study to thoroughly assess the safety profile and PK properties of J147 in healthy subjects. The study will include single ascending dose (SAD) in healthy young and elderly subjects."
  • "Estimated Study Completion Date : January 2020"
Quotes
  • "This Phase 1 trial will test an experimental drug, NDX-1017, in healthy adults and people with mild Alzheimer's disease to evaluate safety, dosing, and action of the drug."
  • "M3 Biotechnology, Inc."
Quotes
  • "This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of NDX-1017 in healthy young and elderly subjects, and elderly subjects with amnestic mild cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate)."
Quotes
  • "Today there are no treatments to prevent, delay or stop the disease progression. "
Quotes
  • "From 1998 through 2017, only four treatments have been approved with another 146 attempts resulting in failure, according to the Adis R&D Insight database."
  • "Alzheimer’s treatments are known as being particularly difficult to develop, as both diagnosis and the recruitment of appropriate trial participants are challenging."
  • "BAN2401 has been met with scepticism since the partners reported promising but confusing 18-month results in July. Yet Eisai remains confident in its continued development."
  • " Eisai Co Ltd on Friday said it has begun phase 3 clinical trials of Alzheimer’s treatment BAN2401, a day after the Japanese drugmaker and U.S. partner Biogen Inc scrapped trials for another Alzheimer’s drug, aducanumab."
  • "Eisai and Biogen were jointly developing three experimental drugs for Alzheimer’s: aducanumab, BAN2401 and elenbecestat, all designed to target the brain-destroying protein beta amyloid."
  • "“As we have believed aducanumab was the best hope for treating Alzheimer’s, ending its trials is big negative surprise,” said analyst Motoya Kohtani at Nomura Securities"
Quotes
  • "Alzheon is developing ALZ-801, a Phase 3-ready pill, one of the few oral drug candidates in advanced stages of clinical testing in Alzheimer’s disease (AD). ALZ-801 is well-tolerated and has the potential to slow or stop the course of the disease in patients with Alzheimer’s."
  • "ALZ-801 could be the first disease modifying treatment for Alzheimer’s"
  • "ALZ-801 Potentially One of the First Approved Disease Modifying Drugs"
Quotes
  • "We are a clinical-stage biopharmaceutical company with a Phase 3-ready program in Alzheimer’s disease and a discovery platform of small molecules for the treatment of neurodegenerative disorders. We are developing these disease modifying treatments by leveraging our expertise in inhibiting protein misfolding and aggregation."
Quotes
  • "Over 5 million people have Alzheimer's disease in the U.S. today. This number will increase significantly in the years ahead. Yet Alzheimer's disease is uncurable."
  • "We are a clinical-stage biopharmaceutical company focused on neuroscience. We translate novel scientific insights into new medicines. That’s a drastic challenge. Our work is complex, risky, labor-intensive, persistent and expensive. And it’s what we love to do. "
Quotes
  • "Our investigational drug candidate, PTI-125, restores the normal shape of FLNA in the brain. This improves the function of multiple brain receptors and exerts powerful anti-neuroinflammatory effects."
Quotes
  • "Abrexa Pharmaceuticals is a developer of drugs designed to treat Alzheimer disease."
Quotes
  • "Abrexa, the San Diego company that licensed J147, will begin early or phase 1 human clinical testing early this year, said Abrexa CEO Ernie Villafranca. Drugs typically pass through three phases of testing. A successful phase 3 trial may qualify the drug for approval."
  • "Abrexa Pharmaceuticals of San Diego has licensed the drug, developed by scientists at the Salk Institute. Privately held Abrexa recently received U.S. regulatory permission to begin human testing."
Quotes
  • "Pre-clinical studies predict our lead therapeutic candidate will slow, halt, and potentially re-establish lost brain function. Our goal is to develop a platform of therapies to address neurological disorders. We are beginning with Alzheimer’s disease, and recruitment is underway for Phase I clinical trials."
Quotes
  • "M3 Biotechnology (M3) is a clinical-stage therapeutics company with a platform of novel disease-modifying regenerative small molecules being developed with the potential to stop disease progression and even restore lost function. While developing a pipeline of assets, M3 has now advanced a lead candidate, for Alzheimer’s disease(AD), to first-in-human Phase I clinical trials assessing safety, toxicity and tolerability while also evaluating a novel biomarker for AD."
From Part 03