ESC 2016 – Prothena builds case for amyloidosis valuation


Prothena is heading towards a big moment perhaps as early as next year, when pivotal data for amyloidosis treatment NEOD001 are due to emerge. Sellside analysts are suggesting near-blockbuster figures for the drug by 2022.

Data outlined at ESC will give no reason for the Prothena bulls to change their minds. The antibody produced high response rates in patients with cardiovascular, renal and neurological symptoms in an open-label dosing study. NEOD001 will need to show a cardiovascular benefit in the phase II Pronto trial if is to confirm its position as the third-most valuable unpartnered asset in biopharma (The stakes rise for unpartnered assets, August 11, 2016).

Binding amyloid

The data outlined yesterday at ESC, which the company has previously disclosed, showed that more than half of patients with cardiovascular, renal or neuropathic symptoms responded to treatment with NEOD001, a monoclonal antibody that binds with the amyloid that accumulates in the light-chain form of the disease, called AL amyloidosis.

This condition is caused by overproduction of misfolded amyloid proteins in the bone marrow. Today, autologous stem cell transplants are sometimes used to treat amyloidosis, or Velcade-based chemotherapies to kill the cells that are producing misfolded proteins. Prothena has gained orphan drug designation for NEOD001, as 10,000-15,000 new cases are diagnosed in the US and EU each year.

The ESC data showed that 19 of 36 patients with cardiovascular complications had a best response, as defined by a reduction of blood biomarkers. Of 35 patients with renal complications, 22 had a response as measured by proteinuria output, and of 11 patients with neuropathic complications, nine showed a response when rated by improvements in a lower-limb neuropathy impairment score.

Potentially pivotal data could come in the form of the phase II Pronto trial readout due at the end of 2017 or early 2018. This study aims to replicate the cardiovascular findings in 100 patients who have responded to an earlier line of chemotherapy or stem cell therapy – renal and neuropathic responses are secondary endpoints.

Beyond that, the phase III Vital trial aims at a first-line population in amyloidosis patients with cardiovascular involvement. Analysts from Barclays note that because of the second-line setting the Pronto might not answer whether patient benefit comes from NEOD001 or prior chemotherapy. The sector might have to wait for Vitality before this becomes clear.

Prized orphan

Should NEOD001 succeed, it could gain a reasonably big chunk of the market. The other main player in amyloidosis is Alnylam, and its RNA-interference approach targets the hereditary, transthyretin-mediated form of the disease.

EvaluatePharma’s consensus of sellside analysts puts 2022 sales of NEOD001 at $946m, giving it a net present value of $2.9bn – substantially above Prothena’s market capitalisation of $1.7bn. The company’s shares have fallen 30% since peaking last November, but still stand at nearly seven times their value when the former Elan spun the group out in December 2012.

As one of the most valuable unpartnered projects in the sector, and active in a prized orphan indication, NEOD001 is likely drawing the attention of big players, and these early data will not have frightened any of them away. The question is whether prospective partners can be patient enough for the late 2018 readout of phase III Vital or are willing to risk it on earlier data.

Study Trial ID
NEOD001-001 NCT01707264
Pronto NCT02632786
Vital NCT02312206

To contact the writer of this story email Jonathan Gardner in Rome at or follow @ByJonGardner on Twitter

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