Our "Community Conversations" series, co-hosted by MTM-CNM Family Connection and Where There's A Will There's A Cure, continued on July 13th 2020, with an excellent presentation and Q&A from Dr. Jim Dowling of the Hospital for Sick Children in Toronto, Ontario.  There are several therapeutic approaches being studied for X-Linked Myotubular Myopathy, all borne out of years of hard work and research by many people, but this one also came about with a bit of "serendipity".  Through an incidental and unexpected outcome in the laboratory while working with a mouse model of MTM, Dr. Dowling's team discovered that the anti-cancer drug tamoxifen seems to have a positive effect on the disease.  This finding was also published by another team of researchers working completely independently.  While the exact mechanism of how tamoxifen effects the disease processes in MTM is still unknown, the preclinical data from the mice is compelling.  Dr. Dowling is now preparing to launch a human clinical trial to test the safety and efficacy of tamoxifen as a treatment for XLMTM.  Watch the replay of the presentation (recorded live on Zoom) here:

On June 29th 2020, MTM-CNM Family Connection and Where There's a Will There's a Cure co-hosted a live Zoom presentation for the MTM-CNM family community.  The guest speaker was Chris Freitag, Chief Medical Officer of Dynacure, who provided an update on the company's "UNITE-CNM" clinical trial.  We were pleased to have over 40 community members tune in live for the presentation and question-and-answer session that followed.  Watch the replay of the video here:

A huge thank you to Chris and the whole Dynacure team!
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For additional information, please visit Dynacure's website.  Note that an additional Q&A document is available in several languages here on Dynacure's Patient page.

​You may have seen some news recently about Zolgensma, a gene therapy that just got approval from the FDA for use in patients with Type 1  Spinal Muscular Atrophy (SMA).  It’s disappointing, but not surprising, that most of the headlines are exclaiming the cost of the treatment ($2.1 million).  Consumer news sources and media are trying to get your attention, and usually amplify the hype without necessarily providing much actual insight.  Here are a few thoughts to consider, especially when extrapolating to gene therapy or similar for MTM/CNM…

1) Type 1 SMA is an early-onset, relatively rapid progression that irreversibly destroys the motor neurons.  After about age 2 the damage is severe, requiring extensive intervention and support and generally fatal over time, though supportive technology such as mechanical ventilation can help, much like with MTM.  This gene therapy stops the progression of SMA, but cannot undo damage that has been done.  Therefore, the approval today was only for patients under age 2.  This underscores the importance of early accurate genetic diagnosis.  MTM, in contrast, generally does not destroy the muscle tissue over time.  Rather, the missing myotubularin acts a bit like a “key” that unlocks the existing muscle machinery.  While it is yet to be proven in human patients, it is hoped that all age ranges would benefit from gene therapy for MTM.  Importantly though, there are other long-term effects of lack of muscle strength, such as joint contractures, that may be more challenging to address in older patients even if muscle strength was restored.

2) Novartis has estimated the cost of medical care for someone with SMA to be about $4M for a span of 10 years.  From an insurance/payers perspective, the $2.1M “price tag” for the gene therapy should be understood relative to the expected benefits.  It is a single-dose treatment, one and done.  If administered early enough (aka under 2 years old) it is reasonable to expect that the $4M in costs are avoided, hence a “savings” of about $2M over 10 years.  Note – this can start to sound like putting a value on a human life, which is an abhorrent concept, but it really is just about setting a reasonable price for the drug, compared to the costs of alternative care.  Steven Pearson, President of the Institute for Clinical and Economic Review (ICER) said, “Insurers were going to cover Zolgensma no matter the price, and Novartis has spoken publicly about considering prices that approached $5 million. It is a positive outcome for patients and the entire health system that Novartis instead chose to price Zolgensma at a level that more fairly aligns with the benefits for these children and their families.”

3) Novartis is offering insurers a payment plan ($425K per year for 5 years), which is an attempt to address the real challenge of how to pay for a treatment like this that is so different from just about any other medical treatment available today.  As the field of gene therapy progresses, these types of alternative payment models will be needed, and this is an area of much work for shaping new public policy and legislation.  The patient & family voice is needed here as well!

4) The development of a gene therapy product takes several years and many many millions of dollars.  The sponsoring company has to foot the bill – often underwritten by investors, private or public, who take on the financial risk given that most drug development efforts never get approved.  The first Phase 1 clinical trial for Zolgensma (called AVXS-101 at the time) began in 2014, so that is about 5 years worth of expensive clinical trials and other development, manufacturing, and regulatory activities (not to mention pre-clinical work) without a single penny in sales.  Eventually, these development costs need to be paid back by successfully marketing a product.  For MTM, Audentes initiated their Phase 1/2 clinical trial “ASPIRO” with the first patient dosed in September 2017, about 1.5 years ago.  While each development timeline and approval pathway is unique and we can’t really connect SMA and MTM, it is generally an encouraging sign that the FDA has granted approval for Zolgensma, and that a novel payment approach is being implemented.  We can certainly continue to hope that the data published so far for ASPIRO will be reinforced by future positive results, leading to expedited approval and access for all who need it.

Yesterday, Audentes Therapeutics provided a quarterly company update, including information on their lead program - clinical development of AT132, a gene therapy product targeting X-Linked Myotubular Myopathy (XLMTM).  Their Phase 1/2 clinical trial, called "ASPIRO", is well underway, and they state:

"...we have recently completed enrollment of the Cohort 2 dose of 3x1014 vg/kg, including three treated patients and one untreated control patient.  We look forward to engaging with the FDA and EMA in the coming weeks to discuss development plans and the potential registration pathway for AT132, and to advance our goal of making this important treatment available to patients living with XLMTM as rapidly as possible."
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Additional information in the full press release may be found on the Audentes website here.  Also, as has been their practice, Audentes has shared a letter with our community, which can be read here.
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