Ann: Successful Competitive Drug Evaluation in Animals, page-12

If like Sarepta there is presently no competition does it benefit them to pay more for something they have hold of regardless?

One could first ask, what exactly does Sarepta “have hold of, regardless”? How have they benefited from, and how do they stand to benefit in future from their PMO chemistry platform?

Obviously, the major benefit to date has been the DMD drug, Exondys 51. It’s Sarepta’s only (FDA) approved drug. Efficacy was so minimal, that the FDA’s approval was conditional on conduct of a further Phase 3 trial to prove the drug’s clinical efficacy. Sarepta has been dragging the chain and, after three years, hasn't come up with that data yet. Meanwhile, Exondys 51 was knocked back by the EMA last year because “further data were needed to show that the very low amounts of shortened dystrophin produced as a result of Exondys treatment bring lasting benefits relevant to the patient.” That pesky efficacy problem again.

The efficacy problem of Exondys 51 probably shouldn't be surprising. On average, less than 1% of ASOs are assumed to reach the correct cellular compartment.

Following Exondys, there’s Vyondys 53, which treats another subset of DMD patients. Sarepta's NDA for Vyondys just got knocked back by the FDA. The FDA had some toxicity concerns. It probably also didn’t help that demonstrated efficacy was exceedingly modest. After almost a year of treatment, mean dystrophin protein increased to just 1.019% of normal (compared with 0.095% at baseline).

Beyond Exondys and Vondys, Sarepta does have further PMO candidates in its pipeline. But they are all targeting subsets of DMD.

It is known that Sarepta is interested in exploring PMOs for conditions other than DMD. It has established the Sarepta Translational Laboratory at Murdoch University for the express purpose of generating data on the applicability of its PMO technology for additional disease targets.

The way I see it, rather than a "hold" on the market, Sarepta has a problem. It has a pipeline of PMO candidates for DMD which must now all be under the same efficacy cloud as Exondys 51 and Vyondys 53. And while the company is keen to apply PMOs to additional disease targets, the same efficacy cloud would hang there as well. If Sarepta tries to dose its way out of the efficacy problem, toxicity questions will be raised.

According to Sarepta’s CEO, PMO technology is precise and safe. It does exon-skipping. But, by his own admission, it has a limitation – it doesn’t get into cells as efficiently as they would like.

Returning to the question - Is there a cost benefit for Sarepta to pay more for something they have hold of regardless?

Perhaps the question should be “What will it cost Sarepta if it doesn’t solve its PMO efficacy problem?”