In the first half of 2020, the number of companies developing advanced medicinal products such as gene, cell and tissue-based therapies passed 1,000 for the first time, according to the Alliance for Regenerative Medicine. That represents an increase of almost 50% since 2015.
The proliferation of active advanced therapy companies has corresponded to an increase in clinical trial activity. At the last count, the sector was running 1,078 clinical trials globally, an increase of 71% over the number of active studies at the end of 2015.
More companies running more clinical trials means more demand for manufacturing capacity. Yet, the strain on manufacturing capacity is about more than just an increase in the number of programs. The types of advanced therapies in development are also affecting demand.
From local delivery to larger systemic doses
Luxturna, the first FDA-approved gene therapy for a genetic disease, is indicative of the original wave of advanced medicinal products. The drug, which Roche acquired through its $4.3bn takeover of Spark Therapeutics, is a locally administered treatment for a rare disease.
Those characteristics limit the capacity requirements for Luxturna. As a drug delivered by subretinal injection to the target tissue, Luxturna is given at a dose of 1.5 x 1011 vector genomes (vg) to each eye to treat a disease that affects 1,000 to 2,000 people in the US.
In contrast, BioMarin tested its systemically delivered hemophilia A gene therapy candidate BMN 270 at a dose of 6 x 1013 vg per kg in men in phase 3. As the average US male weighs around 90 kg, a typical patient may need a 5.4 x 1015 vg dose — 18,000 times the size of a two-eye Luxturna regimen.
BioMarin is also targeting more patients. At 30,000, BioMarin’s initial targeted population of adults with severe hemophilia A is at least 15 times the size of the US market for Luxturna.
The contrast between BMN 270 and Luxturna is representative of a broader shift in the gene therapy space. Having shown efficacy in small patient populations treated via local delivery, the modality is increasingly being used to address far more common diseases via larger systemic doses.
That combination of more clinical trials giving larger doses to bigger patient populations has led to capacity constraints. Last year, William Blair analyst John Kreger said viral vector manufacturers had “elongating waiting lists for new space.” A separate 2019 analysis by consultants at Latham BioPharm Group forecast that demand for adeno-associated virus and lentiviral vectors will exceed outsourced capacity this year.
Those analyses precede COVID-19. Leading COVID-19 vaccines in development at AstraZeneca and Johnson & Johnson are based on viral vectors. AstraZeneca and J&J have discussed plans to make 3 billion doses of their vaccines if they prove to be safe and effective in phase 3.
As analysts at McKinsey have noted, there is considerable overlap between the raw materials and consumables used to make viral vector vaccines and gene therapies, suggesting the pandemic will place further strains on capacity as prophylactic production ramps up to commercial scale.