Amylyx Pharmaceuticals has had a turbulent year. The company, known for its ALS treatment RELYVRIO (ALBRIOZA in Canada), faced a major setback with its Phase 3 PHOENIX trial, which failed to meet its primary endpoints. This, coupled with the voluntary discontinuation of commercial sales in the US and Canada, has painted a picture of a company in retreat. However, a closer look at their Q1 2024 earnings transcript reveals a tantalizing possibility: a potential blockbuster hiding in plain sight within their Wolfram syndrome program.

Wolfram syndrome, a rare, devastating genetic disease, typically leads to multisystem failure, resulting in blindness, deafness, diabetes, and premature death. Currently, there are no approved treatments, leaving those afflicted with a grim prognosis. Enter Amylyx's AMX0035, the same drug at the heart of the company's ALS woes. Here's where things get interesting.

While the drug failed to replicate the success of its earlier CENTAUR trial in the larger PHOENIX ALS study, its interim data from the HELIOS trial in Wolfram syndrome paints a dramatically different story. Not only did AMX0035 show a halt in the decline of beta cell function, a key indicator of the disease's progression, but it actually demonstrated an *improvement* in this function, as measured by the c-peptide response.

Furthermore, a subset of participants even showed an improvement in vision, a finding that flies in the face of the disease's natural history, which typically sees a steady decline in visual acuity often leading to blindness.

These are not just promising results; they are potentially paradigm-shifting. In a disease with zero approved treatments, a therapy that not only slows decline but reverses it in key areas could become the standard of care. The potential market for such a drug, while dealing with a rare disease, could be substantial.

Could Wolfram Syndrome Be Amylyx's Surprise Blockbuster?

While the full data from the 12-participant HELIOS trial is expected in the fall, the interim results from eight participants are compelling. The fact that Amylyx is moving swiftly to engage with the FDA, even before the final data is available, speaks volumes about their confidence in the potential of AMX0035 in Wolfram syndrome.

If the full data confirms the interim findings, the market potential for AMX0035 in Wolfram syndrome could be significant. Consider these factors:

High unmet need: There are currently no approved treatments for Wolfram syndrome. Disease severity: Wolfram syndrome is a debilitating disease with a devastating impact on quality of life and lifespan. Potential for premium pricing: Given the severity of the disease and the lack of alternative treatments, a successful drug could command premium pricing. Orphan drug designation: AMX0035 is likely to receive orphan drug designation, providing market exclusivity and other incentives.

Financial Impact of Discontinued Sales

While the Wolfram syndrome program offers hope, the immediate financial impact of discontinuing RELYVRIO sales is significant. The chart below, based on data from Amylyx's Q4 2023 and Q1 2024 earnings transcripts, illustrates the sharp decline in net product revenue.

Amylyx expects no meaningful revenue from RELYVRIO after March 8, 2024. The company has implemented a restructuring plan, including a 70% workforce reduction, to focus on its pipeline and extend its cash runway into 2026.

A New Chapter for Amylyx?

While it's still early days, the Wolfram syndrome program could be the unexpected ace up Amylyx's sleeve. The market may be currently focused on the company's ALS setback, but if the HELIOS data continues to impress, a compelling narrative shift could be on the horizon.

"Fun Fact: Amylyx was founded by two Brown University undergraduates, Joshua Cohen and Justin Klee, who were inspired to find a cure for ALS after a close friend's father was diagnosed with the disease. Their story is a testament to the power of passion and determination in the face of seemingly insurmountable challenges. Perhaps the Wolfram syndrome program will be another chapter in their inspiring journey."