On the subject of gene therapy, which has been raised a couple of times in this thread….
While gene therapies are often portrayed as “one and done” treatments” which can “cure” a disease, unfortunately, it’s not that simple.
The Muscular Dystrophy Association recently published a brochure titled
Myths and Facts about Gene Therapy which sorts out some common misconceptions about gene therapies from the facts.
Identified as “myths” are:
- Gene therapy is a cure.
- Gene therapy is simple.
- Gene therapy can be reversed.
- Gene therapy is guaranteed to show beneficial results.
- Gene therapy treatments are not yet of proven clinical value.
- Gene therapy is available to treat everyone with a neuromuscular disease diagnosis.
- Any physician can prescribe gene therapy treatment safely.
Identified as “facts” are:
- Researchers have not determined how long the effects of gene therapy treatments will last nor the extent of benefit over time. Factors that may impact the effectiveness and durability of gene therapies include age, treatment dose, and disease progression.
- Gene therapy targets specific cells. A person’s basic genetic composition remains unchanged; only the cells targeted by the therapy change.
- Not everyone will be eligible for gene therapy. Considerations of age, function, pre-existing antibodies, etc., may determine eligibility.
- Early studies show that gene therapy may slow the progression of some diseases.
- Receiving gene therapy may affect access to other types of treatment later.
- Long-term effects of gene therapy remain unknown due to the limited data available.
- Gene therapy affects individuals differently and can cause severe side effects or even death in some.
- Gene therapies require months-long monitoring and treatment of side effects after infusion of the treatment.
- Gene therapy is irreversible and can result in permanent changes to the body.
Other than uncertainties about efficacy, safety and durability, one of the biggest challenges facing gene therapy development at this time is commercial viability.
The following is from
a post I wrote last year on another forum
Two gene therapies for sickle cell disease, developed by Vertex Pharmaceuticals and bluebird bio, were approved in the US late last year. Each costs US$2-3m. To date, only a few dozen patients have begun the process to receive treatment.
Similarly, CSL’s haemophilia B gene therapy Hemgenix, and BioMarin’s haemophilia A gene therapy Roctavian have been slow to sell.
Hemgenix, which was FDA approved in late 2022, is priced at US$3.5m. R &D costs for the drug are reported to have been ~US$1bn and it has been estimated that the vector manufacturing cost alone of one dose could be in the range of US$1-2 m.
Roctavian costs US$2.9m. From Biomarin’s accounts, I have calculated that the drug has cost ~US$1.2bn to date to develop and market. The gene therapy was approved in the EU in August 2022 and in the US in June 2023 and was predicted to be a blockbuster US$2bn drug. Only 3 sales were made in 2023 and BioMarin is rapidly adjusting its plans for both Roctavian and further gene therapy development.
Gene therapies have struggled with a combination of challenges including massive development costs, especially with vector manufacturing costs, safety concerns, payers baulking at the price tags, patient suitability (e.g. having antibodies to the virus used as the vector), patient hesitancy driven by safety concerns and lingering questions over long-term side effects and treatment durability.
While it was only a few years ago that pharma was highly active with both internal R&D and M&A related to gene therapies, the tide now seems to have turned.
Vertex Pharmaceuticals recently announced that it was discontinuing its internal AAV vector research and ending two gene therapy partnerships. One of the reasons provided by the company was that it wanted to focus on programs with clearer paths to market.
This followed
Pfizer’s decision in February to exit gene therapy completely. A key driver in that decision was the commercial failure of Pfizer’s gene therapy for hemophilia B, Beqvez, which was launched in 2023. Pfizer said that there had been limited interest from both patients and doctors for the US$3.5m gene therapy treatment.
CSL launched gene therapy Hemgenix for haemophilia B following FDA approval in November 2022. Sales of Hemgenix have also been slow, with only 12 patients treated in FY24.
In March,
Roche announced a “fundamental reorganization” of Spark Therapeutics, the gene therapy unit it acquired for US$4.3bn in 2019. Re-evaluation of estimated future revenues led Roche to completely write-off Spark, with a full impairment of US$2.4bn in goodwill.
After making 10 gene therapy deals between 2020 and 2022,
Takeda announced in 2023 that it was discontinuing its discovery and preclinical development in AAV gene therapy. Like Vertex, Takeda cited the need for a clearer path to clinical and commercial success.
Last week
, private equity firms Carlyle and SK Capital succeeded in acquiring gene therapy trailblazer
bluebird bio after raising an upfront offer from US$29m to US$45m. Bluebird, which was once valued at more than US$10bn, has three approved gene therapies, approved between 2022 and 2023. However it has struggled to sell the high-priced treatments, to date treating only 60 or so patients across the three therapies.
Sarepta Therapeutics has been more successful with sales of its gene therapy, Elevidys, for the treatment of DMD. Launched in 2023, the drug had US$820m in sales in FY2024. However, in March the company announced that a 16 year old patient had died from acute liver failure related to the AAV-9 vector used in the drug and sales immediately saw a pull back.
In November last year,
Neurogene announced the death of a patient in a Phase 1/2 clinical trial of its gene therapy in the treatment of Rett syndrome. The patient suffered a systemic hyper inflammatory response to the AAV9 vector.
Just last week,
Rocket Pharmaceuticals announced the death of a patient dosed with its AAV9-based gene therapy in a Phase 2 pivotal trial in Danon disease. Ironically, the company believed that the death may have been caused by the immune suppression agent it had added to a pre-treatment preparatory regimen in an attempt to reduce the risk of the type of hyper inflammatory response seen in the Neurogene trial.
I’m not suggesting that there have been no gene therapies which have achieved both clinical and commercial success. Novartis’ Zolgensma for SMA, approved in 2019, which achieved peak sales of US$1.4bn in 2022, is perhaps the best-known example. However, given the considerable development and commercial hurdles that gene therapies still face, this class of drugs is not about to displace all other therapeutic approaches.
(20min delay)