Expanded Access – the Right Applies

Prompted by the current high-profile case of Lisa Stockman Mauriello’s devastating rare disease ALS diagnosis and her family’s fight to access an investigational therapy, tofersen, potentially the only option to alter the course of her disease, we comment on the issues surrounding this case and the possible ethical dilemma this presents whilst applying the long-established EAP regulatory framework. Finally, we ask, could this very public argument have been avoided or averted?

Biogen is not new to the EAP process, how and when it can apply. They have shown compassion in multiple situations and have a well-established set up to manage these essential programs. Considering this specific case, we find their stance surprising noting in particular the company’s statements of impeding the trial and fairness to patients on placebo.

We suggest the company should be aware that this would not be the case in Lisa’s case, affording patient access to tofersen cannot impede a trial that is closed to recruitment or interrupt progress to ultimately get the drug approved and commercially available.

Bearing in mind the regulations supporting the use of EAP’s and the extensive experience within the company we do not think Biogen’s decision necessarily makes sense from a regulatory perspective. 

EAP’s are often run alongside randomized clinical trials to potentially include those patients who do not meet inclusion criteria or who cannot participate for other reasons. Lisa’s physician states” her disease is a genetic form of ALS stemming from a mutation in the SOD1 gene; precisely the kind of ALS Biogen is developing the drug for.”

According to clinicaltrials.gov the ALS study in question is closed to recruiting. Hence, this is clearly not a case where this patient, if eligible, can enroll in the trial and therefore the only way to receive treatment is through an EAP supported by her physician. 

In our work at RareiTi and with decades of prior experience in early access situations, we know this scenario well. We know this is not an isolated case today and neither will it be the last.

In 1987, lobbying hard to gain access to therapy still in trials, people with HIV/AIDS and an impending death sentence had no other treatment options available. FDA recognised the need to make provision for patients with exceptional need to potentially gain access to an investigational therapy. Swiftly developing a regulatory pathway, it worked.

The US EAP regulation (21 CFR 312.300) we know today (Expanded Access: Single patient IND, Intermediate Sized Patient Population and Treatment IND or Protocol) followed. Finalized in 2009 and setting a now well-established regulatory framework for providing access to investigational drugs.

Despite its positive impact since and changing views significantly, we still find today that some pharma and biotech companies remain fearful of allowing access (safety, potential impact on NDA/BLA filing) leading to imperfect, if not impasse situations like Lisa’s. Unfortunately, this is not uncommon in rare disease or other debilitating or terminal conditions leaving patients and their families with no options at all.

Of course, a pharma/biotech company is not required to provide patient access (compassionate use) to their investigational drug(s), they are only required to have an EAP policy on their website since the passing of the 21st Century Cures act. This is not necessarily a backstop we wish to eradicate under any circumstances, however, there are specific circumstances that must apply in these exceptional situations that we should consider further. 

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