Known to many as Lou Gehrig's disease, ALS — or amyotrophic lateral sclerosis — has presented a major challenge for drug developers. Like many diseases of the brain, the complicated biology behind ALS has resulted in new, promising therapies failing time and again.
Among the few experimental drugs that have made it to the final stages of human testing is tofersen. Developed by Ionis Pharmaceuticals and Biogen, tofersen is meant for a very small subset of patients with certain genetic abnormalities that can cause ALS. Specifically, the drug is supposed to stop these patients from producing a protein called SOD1, which, when mutated, can give rise to the disease.
Biogen and Ionis are currently testing tofersen in a placebo-controlled study of about 180 adults with inherited ALS. The study should have results in July, and if the drug looks safe and effective, the companies plan to ask for approval.
But many patients fear they can't wait that long. ALS is often a rapid disease, causing weakness, fatigue and loss of muscle control earlier on, then paralysis and early death as it progresses.
With so few treatment options, Biogen and Ionis have faced calls to make their drug more widely available. While they had resisted, on Tuesday, Biogen announced a new, two-part program that would expand access to tofersen ahead of the drug being submitted for approval.
The first part of the program is set to begin in mid-July, after patients in that late-stage study's placebo group are allowed to switch to tofersen treatment. At that point, "compassionate use access" will be granted to patients outside the trial — though, only to those with SOD1 mutations who are the most rapidly progressing.
The second part would begin in the fall, and hinge on the study generating positive data. If that's the case, and no further studies are required by regulators, Biogen said it would expand early access to the broader SOD1-ALS population.
"Answering questions about access for new medicines outside of clinical studies is neither simple nor fast," Biogen said in a statement. "Among the ethical imperatives in any access program are assuring that all patients receive equal treatment and priority and preserving the integrity of ongoing studies. Addressing these imperatives takes time and requires careful thought."
According to Biogen, one of the biggest imperatives has been ensuring that patients in the placebo arm of its study will have fair and timely access to tofersen. In fact, the company had previously refused to establish an early access program, citing the ethical dilemma it would create.
"These patients agreed to participate in our study acknowledging the risk that they may not receive tofersen," Al Sandrock, Biogen's head of research and development, wrote in a recent letter posted to the company's website. "We cannot overlook these patients when considering questions of broader access, and cannot keep them on placebo while at the same time offering tofersen to those outside of our study."
Biogen's new program addresses these concerns by opening up access only once the placebo-treated patients have a chance at tofersen treatment. The company said it made this decision after consulting with a variety of stakeholders, including regulators, clinical investigators, ethicists and patient advocates.
Still, Biogen's reversal suggests the company may be under more pressure than before. The company has come under fire from individual patients, with one petition for access to tofersen having accumulating almost 110,000 signatures on the website change.org.
Biogen isn't alone either. The Food and Drug Administration recently experienced backlash from patient advocates, including The ALS Association, after it requested more data for a closely watched drug being developed by Amylyx Pharmaceuticals. The ALS Association criticized the FDA for not following its own guidance on drug approvals, and for not trying to bring forth new ALS treatments as urgently as regulators in other countries.