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FDA Breakthrough Therapy Designation #59: Genentech And Diabetic Retinopathy


Genentech, receives this week the FDA Breakthrough Therapy (BTD) for Lucentis (Ranibizumab Injection) for diabetic retinopathy. Lucentis, given by injection into the eye, has FDA approval for the following indications :

•    Diabetic Macular Edema (DME)

•    Neovascular (wet) Age-Related Macular Degeneration (AMD)

•    Macular edema following Retinal Vein Occlusion (RVO).

Diabetic retinopathy is a complication of diabetes that results in damaging the eye’s retina, that can lead to poor vision, vision loss, and other vision problems. There is currently no FDA approved treatment for diabetic retinopathy.

According to an online EyeWireToday article, for Genentech’s Lucentis the FDA :

•    In September 2014, accepts a supplemental Biologics License Application (sBLA) & grants Priority Review for diabetic retinopathy

•    Confirmed action date for the BLA is 02/06/14.

In September 2014, Regeneron Pharmaceuticals receives the FDA BTD for Eylea (Afibercept) injection for the same indication. Eylea is currently approved in the U.S., European Union (EU), and other countries for the treatment of wet Age-Related Macular Degeneration (AMD), macular edema following Central Retinal Vein Occulsion (CRVO), and DME. In the U.S. and the EU, regulatory submissions have been made for macular edema following Branch Retinal Vein Occulsion (BRVO).

Earlier in December, Regeneron Pharmaceuticals announces that the FDA accepts for Priority Review the sBLA for Eylea, for diabetic retinopathy in patients with DME, with a target action date of March 30, 2015.

The watch is on to see which FDA BTD medicine for diabetic retinopathy is approved first, which will be the first to market, how will both medicines compete in the market (i.e. price), and how will each distinguish itself from the other.



FDA BTD Approval Chart

FDA BTD Statistics Chart.

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

Hunter Syndrome: Shire Collaboration And FDA Acceptance Of ArmaGen’s IND


ArmaGen, a Calabasas, California-based clinical stage biotechnology company  developing therapies for severe neurological disorders, announces December 11th, that the FDA’s Investigational New Drug (IND) application for the company’s lead product candidate, AGT-182 for Hunter Syndrome (Muchopolysaccharidosis II or MPS II), is accepted and is now active. This will enable a Phase I clinical trial, to assess the safety and tolerability of AGT-182 in adult male patients with Hunter Syndrome, to start in the first quarter of 2015.

Hunter Syndrome is a progressive, rare, and severe Lysosomal Storage Disorder (LSD), caused by inadequate activity of the enzyme that breaks down complex sugars – Iduronate-2-Sulfatase (IDS). Current treatments are not expected to cross the Blood-Brain Barrier (BBB) in relevant amounts, and thus do not deal with the neurological complications of Hunter Syndrome.

AGT-182 is an investigational Enzyme Replacement Therapy (ERT) for Hunter Syndrome. What is unique about AGT-182 is the proprietary technology designed to “take advantage of the body’s natural system for transporting products across the BBB, by binding to the same receptor that delivers insulin to the brain”. AGT-182 has Orphan Drug Designation (ODD) from both the FDA (May 2013)  and the European Medicines Agency (EMA).

In July 2014, ArmaGen enters into a worldwide licensing and collaboration agreement with Shire plc to develop AGT-182 for treatment of both the central nervous system and somatic manifestations of Hunter Syndrome. Under the agreement:

… Shire receives worldwide commercialization rights for AGT-182. ArmaGen will receive payments up to approximately $225 million, including an initial upfront payment of $15 million in cash and equity, an additional equity investment, R&D funding, development and sales milestones, in addition to future royalties up to double digits. The collaboration between ArmaGen and Shire on AGT-182 will be managed by a joint steering committee, with representatives from both companies. ArmaGen will be responsible for conducting a Phase 1/2 study of AGT-182 … Shire will be responsible for further clinical development, including Phase 3 trials, registration and commercialization of AGT-182 worldwide.

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

Rare Disease Stem Cell Research Collaboration: Alexion Pharmaceuticals And University Of Connecticut


On December 11th, The University of Connecticut’s Stem Cell Institute announces a stem cell research collaboration with Alexion Pharmaceuticals, to find new drug candidates for treating rare diseases. Alexion Pharmaceuticals is a Connecticut-based global biotechnology company developing treatments for ultra-rare diseases.  The collaboration will focus on the discovery and testing of therapeutic candidates to treat rare diseases that have no effective treatments. Financial terms of the collaboration have not yet been released.

In 2006, in response to the US federal government placing restrictions on the funding and use of stem cell research, the state of Connecticut signs a law authorizing the use of public funds to finance human stem cell research. The law commits $100 million for the period, 2007 – 2017, to support this type of research. The law establishes both a competitive process for awarding research grants and a Stem Cell Research Advisory Committee responsible for distributing funds based on legal, scientific, and ethical integrity of the research being done.

According to an online article:

“The collaboration between the school’s stem cell program and Alexion will build upon the work of Dr. David Goldhamer, professor of molecular and cell biology and associate director of UConn’s Stem Cell Institute. Goldhamer has identified the offending cell type that drives a group of diseases, and has developed physiologically relevant disease models. Models Goldhamer has developed will be used in the collaborative research to further understand rare diseases and to test potential drugs that could be used to treat them.”

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.


Translarna (Ataluren): PTC Therapeutics’ New FDA Orphan Drug Designation For Mucopolysaccharidos I


PTC Therapeutics receives FDA Orphan Drug Designation (ODD) on December 10th, for its lead product candidate, Translarna (Ataluren), for the treatment of Mucopolysaccharidosis Type I.

Mucopolysaccharidosis (MPS), is part of the rare disease group, Lysosomal Storage Disorders (LSDs). LSDs are a group of rare inherited metabolic disorders that are usually progressive, resulting in a patient’s debilitating health. LSDs are made up of over 40 disorders, where each disorder is caused by a deficiency of a specific enzyme that is responsible for the metabolism of lipids, glycoproteins, or mucopolysaccharides. Several distinct clinical types and numerous subtypes of MPS have been identified  based on the name of the enzyme deficiency :

•   MPS I H Hurler a-L-Iduronidase
•   MPS I S Scheie a-L-Iduronidase
•   MPS I H-S Hurler-Scheie a-L-Iduronidase
•   MPS II Hunter Iduronate sulfatase
•   MPS III A Sanfilippo A Heparan N-sulfatase
•   MPS III B Sanfilippo B a-N-Acetylglucosaminidase
•   MPS III C Sanfilippo C Acetyl CoA: a-glycosaminide acetyltransferase
•   MPS III D Sanfilippo D N-Acetylglucosamine 6-sulfatase
•   MPS IV A Morquio A Galactose 6-sulfatase
•   MPS IV B Morquio B B-Galactosidase
•   MPS VI Maroteaux-Lamy(arylsulfatase B) N-Acetylgalactosamine 4-sulfatase
•   MPS VII Sly B-Glucuronidase
•   MPS IX Hyaluronidase
•   MPS II I-Cell N-acetylglucosamine-1-phosphotransferase
•   MPS III Psuedo-Hurler polydystrophy N-acetylglucosamine-1-phosphotransferase.

MPS I is caused by a deficiency of an enzyme, alpha-L-Iduronidase. MPS I is also referred to as Hurler, Hurler-Scheie, and Scheie Syndromes. MPS I occurs in approximately 1/100,000 newborns globally.

Currently in the US, Aldurazyme (Laronidase) is approved by the FDA for patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I), and for patients with the Scheie form who have moderate to severe symptoms. Aldurazyme is an Enzyme Replacement Therapy (ERT) injection for MPS I. In the European Union (EU), Aldurazyme is approved for MPS I to treat the non-neurological symptoms of the disease.

Translarna, is a novel, orally administered small-molecule compound for the treatment of genetic disorders due to nonsense mutation. Per PTC Therapeutics’ website:

“Nonsense mutations are implicated in a variety of genetic disorders and create a premature stop signal in the translation of the genetic code contained in mRNA, which prevents the production of full-length, functional proteins. We believe that ataluren interacts with the ribosome, which is the component of the cell that decodes the mRNA molecule and manufactures proteins, to enable the ribosome to read through premature nonsense stop signals on mRNA and allow the cell to produce a full-length, functional protein. As a result, we believe that ataluren has the potential to be an important therapy for muscular dystrophy, cystic fibrosis and other genetic disorders for which a nonsense mutation is the cause of the disease.”

Ataluren also has FDA ODD for the following indications:

•   Cystic Fibrosis resulting from a nonsense mutation, nmCF (September 2004)

•   Duchenne Muscular Dystrophy, nmMD (January 2005)

•   Spinal Muscular Atrophy (March 2008).

In August 2014, Translarna is granted conditional marketing authorization in the EU for the treatment of nmDMD in ambulatory patients aged 5 years and older. Ataluren also has European Medicines Agency (EMA) ODD for the following indications:

•   Duchene Muscular Dystrophy (May 2005)

•   Becker Muscular Dystrophy (July 2012).

FDA ODD Database Record For PTC Therapeutics’ Mucopolysaccharidosis I Indication 

Generic Name: Ataluren
Trade Name: Translarna
Date Designated: 12-10-2014
Orphan Designation: Mucopolysaccharidosis Type I
Orphan Designation Status: Designated
FDA Orphan Approval Status: Not FDA Approved for Orphan Indication
Sponsor: PTC Therapeutics, Inc. 100 Corporate Court South Plainfield, NJ 07080


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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

FDA Breakthrough Therapy Designation And Oncology Statistics


As reported widely in the media and the literature, oncology indications make up a significant percentage of FDA Breakthrough Therapy (BTD) Designations. The IMS Institute for Healthcare Informatics publishes in November 2014 the report, “Global Outlook For Medicines Through 2018”. This report takes a look at medicines and global spending levels through 2018.

Here are a few observations for global drug trends from the IMS November report:

•   Global drug spending is forecast to reach nearly $1.3 trillion by 2018 – a 30% increase over 2013

•   Increase in the # of Orphan Drug Designation (ODD) & Breakthrough Therapy Designation (BTD) applications and steady approval rates are the expected trend

•   In 2014, as of this IMS Report publication date, there are 12 drugs approved in the US that have a FDA BTD

•   1st FDA BTD biologic (Meningococcal Group B vaccine) is approved

•   Increase in the # of immunotherapy oncology treatments – with many receiving the FDA BTD, with potential for multiple follow-on indications

•   Acceleration of oncology medications, with many getting FDA BTD

•   46% of FDA BTDs are for an oncology indication

•   New immunotherapies, PD-1 & CDK inhibitors, are becoming a strong growth trend for oncology indications

•   Globally, oncology is 31% of the total drug pipeline, with biologics making up 45% of the late stage oncology pipeline

•   Spending on oncology medicines globally is expected to grow by over 50% to exceed $100 bllion in 2018.


The Orphan Druganaut Blog has supplied the following statistics for oncology products:

•    53 % of the FDA BTDs receiving approval are for an oncology indication (as of 12/03/14)

•    Of the 58 FDA BTDs reported by sponsor companies (as of 12/01/14), 43% are for an oncology indication.

Thus the FDA Breakthrough Therapy Designation is playing an important role in helping to accelerate drug development and the approval process for oncology indications.

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

Shire And Cystic Fibrosis Foundation: Rare Disease Drug Collaboration


Shire and the Cystic Fibrosis Foundation Therapeutics Inc. (CFFT), the nonprofit drug development affiliate of the Cystic Fibrosis Foundation (CFF), announce on December 10th, a $15 million multi-year research agreement to support Shire’s Messenger RNA (mRNA) Technology platform for Cystic Fibrosis (CF). The potential treatment is designed with the goal of “boosting lung function and decreasing the number and severity of lung infections”.

Per the CFF news release :

Shire is working to develop a unique technology to deliver normal messenger RNA for CFTR directly to the lungs, where it can be used by the body’s cellular mechanisms to produce working copies of the protein. Messenger RNA is a conveyor of genetic code critical to proper function of the body’s proteins. If successful, the potential messenger RNA therapy could benefit all people with cystic fibrosis, regardless of an individual’s mutations.

The first phase of Shire’s CF program is focusing on evaluating the dosing and safety of the therapy in the lab.

Just last month in November, Royalty Pharma announces its acquisition of royalties on Vertex Pharmaceutials’ CF treatments owned by CFFT for a cash payment of $3.3 billion. CFF plans on reinvesting the money into new research efforts and expanding patient programs. According to a Bloomberg online article :

The transaction is part of a growing trend in philanthropy called mission investing. In mission investing, instead of giving research grants as charity, philanthropies act more like business partners and expect a share of profits stemming from their gift, according to Aaron Dorfman, executive director of the National Committee for Responsive Philanthropy.

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.

Immunotherapy Start-Up Juno Therapeutics: Upcoming Initial Public Offering (IPO)






It has been a busy 2014 for the Seattle-based immunotherapy start-up Juno Therapeutics (founded in 2013) :

•    April 24th, completion of $176 million Series A round

•    August 5th, close of $134 million Series B round

•    September 22nd, named one of FierceBiotech’s 2014 Fierce 15

•    November 13th, FDA Orphan Drug Designation (ODD) for its lead product candidate JCAR015, a chimeric antigen receptor (CAR), for Acute Lymphoblastic Leukemia (ALL)

•    November 17th filing of a S-1 Form, with the US Securities and Exchange Commission (SEC)

•    November 24th, FDA Breakthrough Therapy Designation (BTD) for JCAR015 for the treatment of relapsed/refractory B-Cell Acute Lymphoblastic Leukemia (r/r ALL)

•    December 5th, announcement that the company enters into an agreement to get a license from Opus Bio for a CAR-T cell product candidate targeting CD22 (protein expressed on most B cell leukemias & lymphomas)

•    December 8th, ASH (American Society of Hematology) Meeting presentations, showing significant outcomes in clinical trials with B-cell cancers.

Juno Therapeutics files on December 9th with the US SEC, Amendment No. 2 to the S-1 form. The company says that it will sell up to about 9.3 million shares of common stock at $15 – $18 per share, and expects to give its underwriters an option to buy about 1.4 million shares. According to the IPO tracker Renaissance Capital, the offering is expected to price the week of 12/15/14 and “at the midpoint of the expected range, Juno Therapeutics would command a fully diluted market value of nearly $1.5 billion, which would make it the largest biotech of 2014 by market cap.”

The underwriters are Morgan Stanley, JPMorgan, Goldman Sachs, and Leerink. The company plans to list on the NASDAQ under the symbol “JUNO”.

Per the December 9th Amendment No. 2 filing, the net proceeds are to be used as follows:

•   $25 million to advance its lead product candidate JCAR015 through Phase II clinical trials & the filing of a FDA Biologics License Application (BLA) for relapsed/refractory B-Cell Acute Lymphoblastic Leukemia (r/r ALL)

•   $20 million to advance JCAR017 through Phase I/II clinical trials & potential registration trial in r/r Non-Hodgkin Lymphoma (NHL)

•   $15 million to develop additional product candidates

•   $30 million for research & development capabilities

•   $20 million for manufacturing capabilities

•   Remaining $s for working capital/general corporate purposes.

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Copyright © 2012-2014, Orphan Druganaut Blog. All rights reserved.


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