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A Big Step for Gene Therapy

June 1, 2019

This past Friday started off bright and early with the sound of rushing water in my basement….never a good sound. The water heater emergency pressure valve had released. Thank goodness I was in the kitchen when it happened and heard the water. I quickly turned off the water supply, and the mess was cleaned up and the problem fixed in time to get to an outpatient surgery center for a procedure my older son was having done.

Being a veteran of hospitals (although usually for Chelsea and not other family members) I brought my laptop along so I could keep working. It was in the recovery room waiting for my son to wake up that I let out a gasp that brought nurses and doctors running. After assuring them that he was fine I proceeded to inform them that the FDA has just approved gene therapy for spinal muscular atrophy (SMA). If they wondered why the news had elicited such a gasp, they didn’t ask.

While the news came as no surprise, as I and everyone following gene therapy had been anticipating it all month, it was nevertheless exciting and wonderful. It was also somewhat personal having met many of the key players over the years and reflecting on the journey that will now change the lives of patients with SMA and has promise to change the lives of patients with Rett.

RSRT started funding gene therapy efforts back in 2010. Gene therapy was still a bad word back then due to lots of failures and hype. But those that believed in gene therapy persevered. People like Brian Kaspar and Jim Wilson. And it is because of their boldness that lives are now being saved.

I was with Brian Kaspar in May of 2014 at a Gene Therapy Consortium meeting I had organized, the day after the first ever SMA patient was dosed with the now approved gene therapy product, Zolgensma. That little baby was the first SMA patient to ever receive gene therapy using AAV9 and he was also the first patient to have received such a large a dose of gene therapy. Brian was receiving updates on the patient every 15 minutes or so. He was jumpy, as was I. Fellow scientists had warned him that he risked killing these little patients. Fortunately he didn’t succumb to those fears. The days passed and the patient was doing fine…better than fine actually.

Randy Carpenter, our CMO, and I went to visit Nationwide Children’s Hospital where the trial took place and met Dr. Jerry Mendel, the principal investigator of the trial and we toured the facilities where the gene therapy product was made.

When it became evident that RSRT’s Gene Therapy Consortium was generating efficacy results in Rett mice that were far greater than with any other therapeutic tested to date I prayed and hoped that AveXis would make Rett as their next indication. Fortunately, that actually came to pass. Next, AveXis had to be granted a license to use AAV9 for Rett by the company that owned the intellectual property. My colleague Dr. Carpenter helped to facilitate that transaction and another hurdle was successfully accomplished. Incidentally, AAV9 was discovered by Jim Wilson who is now funded by RSRT as a member of our Gene Therapy Consortium 2.0.

The next big hurdle will be to see what kind of results the Rett gene therapy trial yields. AAV9 is especially suited to infiltrate the types of cells in the spinal cord that need to be targeted for SMA. Rett however is a diffuse brain disorder. How well will AAV9 target the various parts of the brain? Will the results be dramatic or subtle? What symptoms will improve and by how much? How much will age play a role? Will there be any side effects? These are all questions on my mind.

Accessibility to gene therapy is also a concern. The SMA product is priced at $2.125 million per patient ($425,000 annually for 5 years) and is being billed as the most expensive drug in the world. I find this somewhat misleading however. There are plenty of drugs that need to be taken chronically, year after year, that end up costing much more than Zolgensma, which is a one and done cure. For comparison sake below is a list of drugs with their annual cost.

We know that caring for an individual with Rett is also hugely expensive: hospitalizations, surgeries, doctor visits, therapies, drugs, formula, diapers, at home nurses/CNA, special education including one-on-one aides, durable equipment, assisted communication devices, wheelchair vans, remodeling homes, not to mention opportunity cost of lost wages (child and sometimes parents) and on and on and on.

RSRT is currently funding a burden of disease study to get a handle on the economics of caring for our children over the course of their lifetime. This will be important information to have on hand as more therapeutics are developed and priced, whether gene therapy or not.

Importantly, no one expects families to come up with the funds to pay for gene therapy for their kids. It is imperative that insurance companies step up and pay. It is clear that Novartis has been working behind the scenes to negotiate with insurance companies, both private and government, to come up with payment strategies. Zolgensma is paving the way, hopefully one that Rett will follow.

But I am getting ahead of myself. Before worrying too much about price and accessibility we need to see if the AveXis/Novartis gene therapy works for Rett.

Regardless of the outcome I promise every parent, grandparent, sibling, relative and friend reading this blog that RSRT will not rest until we have a cure.

And when that cure comes it will be because of all of our generous supporters and the families that fundraise for RSRT to bring treatments like gene therapy from theory to reality. You, like the scientists we are funding, are also bold. Thank you!

Annual Costs

Actimmune | Horizon Pharma | $627,864 (Osteopetrosis)

Mmyalept | Aegerion Pharmaceuticals | $555,936 (Lipodystrophy)

Daraprim | Vyera Pharmaceuticals | $540,000 (Toxoplasmosis)

Cinryze | Shire | $529,692 (Angioedema)

Takhzyro | Shire | $529,680 (Angioedema)

Chenodal | Retrophin, Inc | $510,840 (Gallstones)

Juxtapid | Aegerion Pharmaceuticals | $488,704 (Cholesterol)

H.P. Acthar | Mallinckrodt Pharma | $488,052 (Infantile Spasms)

Tegsedi | Akcea Therapeutics | $415,200 (Hereditary Transthyretin| Mediated Amyloidosis)

Ravicti | Horizon Pharma | $402,864 (Urea Cycle Disorders)

Vitrakvi | Bayer And Loxo Oncology | $393,600 (Cancer)

Firazyr | Shire | $389,616 (Angioedema)

Curpimine | Valeant Pharma | $377,112 (Wilson's Disease And Cystinuria And Rheumatoid Arthritis)

Sovaldi | Gilead | $336,000 (Hepatitis C)

Viekira Pak & Xr | Abbvie | $333,276 (Hepatitis C)

Orfadin | Apotek Produktion & Laboratier | $326,934 (Hereditary Tyrosinemia)

Tibsovo | Agios Pharma | $323,380 (Leukemia)

Cerdelga | Sanofi | $312,000 (Gaucher Disease)

Remodulin | United Thera | $305,592 (Pulmonary Arterial Hypertension)