FDA Approves Vimizim for Treatment of MPS IVA

morquiotitleFDA NEWS RELEASE

For Immediate Release: Feb. 14, 2014
Media Inquiries: Andrea Fischer, 301-796-0393, andrea.fischer@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves Vimizim to treat rare congenital enzyme disorder
First drug to receive Rare Pediatric Disease Priority Review Voucher

The U.S. Food and Drug Administration today approved Vimizim (elosulfase alfa), the first FDA-approved treatment for Mucopolysaccharidosis Type IVA (Morquio A syndrome). Morquio A syndrome is a rare, autosomal recessive lysosomal storage disease caused by a deficiency in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Vimizim is intended to replace the missing GALNS enzyme involved in an important metabolic pathway. Absence of this enzyme leads to problems with bone development, growth and mobility. There are approximately 800 patients with Morquio A syndrome in the United States.

Vimizim was granted priority review. An FDA priority review provides for an expedited review of drugs for serious diseases or conditions that may offer major advances in treatment. Vimizim is also the first drug to receive the Rare Pediatric Disease Priority Review Voucher – a provision that aims to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

“This approval and rare pediatric disease priority review voucher underscores the agency’s commitment to making treatments available to patients with rare diseases,” said Andrew E. Mulberg, M.D., deputy director, Division of Gastroenterology and Inborn Errors Products in the FDA’s Center for Drug Evaluation and Research (CDER). “Prior to today’s approval, patients with this rare disease have had no approved drug treatment options.”

The safety and effectiveness of Vimizim were established in a clinical trial involving 176 participants with Morquio A syndrome, ranging in age from 5 to 57 years. Participants treated with Vimizim showed greater improvement in a 6-minute walk test than participants treated with placebo. On average, patients treated with Vimizim in the trial walked 22.5 meters farther in 6 minutes compared to the patients who received placebo.

The most common side effects in patients treated with Vimizim during clinical trials included fever, vomiting, headache, nausea, abdominal pain, chills and fatigue. The safety and effectiveness of Vimizim have not been established in pediatric patients less than 5 years of age. Vimizim is being approved with a boxed warning to include the risk of anaphylaxis. During clinical trials, life-threatening anaphylactic reactions occurred in some patients during Vimizim infusions.

Vimizim is marketed by Novato, Calif.-based BioMarin Pharmaceutical Inc.

For more information:

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.



A Response to Shire

flemming2Hi Everyone,

Last night on NBC news, Shire Pharmaceuticals released a statement for the media (no personal interviews, sadly).  Our response to their statement is included below.

Once again, I’m calling on Shire to publicly address our case, point by point, with their rationale for not supporting expanded access use for Jack Fowler.  I’m happy to present the document publicly, and I call on Flemming Ornskov to be open, transparent, and honest with the Fowler family and the public, and provide the reasons that Shire cannot live up to their public motto by “Being Brave” to #SaveJack.


Shire’s statement reads:

We remain deeply sympathetic to Jack Fowler and his family. Patients have been, and will always be, at the heart of what we do, and have driven our desire to research potential new therapies for more than 20 years. Guidance from regulatory agencies is that expanded access to investigational medicines and devices outside of a clinical study setting should be based on the existence of compelling evidence of efficacy, or the drug’s benefit, and safety. Efficacy is typically studied in later stage trials; these data are not yet available for our investigational treatment as we have only just initiated our Phase II/III study. Shire does support, and has provided, expanded access at the appropriate stage in the development process-when clinically validated efficacy and safety information is available. We remain focused on completing our Phase II/III trial with the hope of making our investigational treatment available to as many Hunter syndrome patients as possible, as quickly as possible.

Source: http://www.nbcchicago.com/news/local/Parents-Fight-To-Get-Drug-For-Sick-Son-242704721.html#ixzz2rsxvW0L8

A few notes (in order of rebuttal):

1.  “Patients have been, and will always be, at the heart of what we do…”

  • Flemming Ornskov specifically said to the Fowler family, and I was present to witness this statement: “We don’t deal with patients.  We don’t deal with families.  We are in the business of developing products.”

2.  ” Guidance from regulatory agencies is that expanded access to investigational medicines and devices outside of a clinical study setting should be based on the existence of compelling evidence of efficacy…”

Richard Klein, a member of the Office of Special Health Issues at the FDA (the regulatory body authority that guides expanded access protocol) has stated a few things regarding efficacy (source information at bottom):

  • “Confidence of safety is more important than efficacy.”  
  • With regards to safety confidence, “for a patient with an immediate life-threatening condition, evidentiary burden is low.”  
  • Efficacy (and safety) of early phase investigational drugs not proven – and sometimes not known; however, might be given in hope of direct benefit to patient.”

3. “Shire does support, and has provided, expanded access at the appropriate stage in the development process-when clinically validated efficacy and safety information is available.”

  • Shire did not have a compassionate (or expanded use) policy in place when we approached them about Jack Fowler.  I have the transcript of our teleconference where we questioned them on this fact, and they agreed that there should be something in place but that there was not.  While they may have allowed this type of request in the past, they have had not set criteria to allow expanded access for patients until January of 2014, long after we approached them to #SaveJack.  Incidentally, those criteria are riddled with errors, and I will post our response to that policy soon.

4.  “We remain focused on completing our Phase II/III trial…”

Expanded Access to an investigation drug outside the clinical trial setting can HELP with clinical trials and, in some cases, speed up approval of a drug.  As well, any adverse affects that transpire while a patient is receiving Expanded Access to a medication DOES NOT IMPACT THE CLINICAL TRIAL in the slightest.  See below, direct from the FDA:

  • In an email to The Isaac Foundation, Janet Woodcock from the FDA stated, “…in our collective knowledge here at CDER, adverse events occurring during the development program have not delayed the programs.  In one case, we know the drug development was actually accelerated.”
  • The FDA has made a very clear statement on this matter, and included this information in their report on Expanded Access.   This report states: “Although adverse events first identified during expanded access use of certain drugs have been included in the drugs’ approved product labeling, we are unaware of any cases in which adverse event information obtained from expanded access use has resulted in denial of approval for a product.”
  • Former FDA Director Dr. Lester Crawford stated “The FDA, categorically, does not attach special significance to adverse events reported from such expanded access program as (one critic) has tried to join.  We recognize that these programs involve less-controlled use of new drugs, and we assess the reported data accordingly.  The development of a new medication is not slowed by side effects occurring outside clinical trials.”

Source from Richard Klein: http://www.fda.gov/downloads/ForIndustry/DevelopingProductsforRareDiseasesConditions/OOPDNewsArchive/UCM294794.pdf