Rare disease drug from LEO's Timber felled by failed study

Just a few months after buying Timber Pharma, LEO Pharma has revealed that the main drug it acquired as part of the deal has failed a phase 3 trial.

Timber's lead candidate TMB-001 for rare skin disease congenital ichthyosis failed to meet its efficacy objectives across the board in the ASCEND trial and will not support a planned regulatory filing, said LEO in a statement.

The drug is not being tested for any other indications, although it has been mooted as a potential treatment for severe acne and/or sebaceous hyperplasia, as well as Darier disease, a rare condition that causes scaly skin papules.

TMB-001 is an ointment formulation of the well-established dermatology therapy isotretinoin, which LEO picked up for a bargain price – just $14 million upfront and with a total potential value of $36 million – shortly after Timber filed for bankruptcy protection last year.

That was a modest wager on a drug that stood a chance of becoming the first FDA-approved topical therapy for congenital ichthyosis, a collection of around 20 rare skin disorders that cause dry, scaly skin, sometimes over the whole body.

Most cases are mild, but Timber was targeting moderate to severe forms that can be highly debilitating and even life-threatening.

ASCEND was testing TMB-001 in patients aged six and over with either autosomal recessive congenital ichthyosis (ARCI), which causes severe symptoms in around two-thirds of patients, and the somewhat milder X-linked recessive ichthyosis (XLRI) form.

The trial did not show a statistically significant difference between the proportion of patients treated with TMB-001 responding to treatment after 12 weeks compared with patients treated with the ointment without isotretinoin.

At the moment, treatment of congenital ichthyosis relies on topical creams and emollient oils to hydrate the skin, with systemic retinoids like isotretinoin used for more severe cases, as they have well-recognised side effects, including causing birth defects if taken during pregnancy, extreme sensitivity to sunlight and eyesight, and hair, muscle, or joint complications.

"We are disappointed and saddened by the results of the phase 3 trial. After encouraging phase 2b results, we observed an unexpectedly high vehicle response in this trial," said John Koconis, chief executive of Timber, which became a wholly-owned subsidiary of LEO after the takeover.

"We had hoped that TMB-001 could have been a new potential treatment to help children and adults suffering from moderate to severe congenital ichthyosis and to allow them to live a quality life they had previously not known," he added.

While the future of TMB-001 has been thrown into doubt, Timber's pipeline also includes TMB-003, a topical formulation of endothelin A antagonist sitaxsentan in pre-clinical testing and with potential in sclerotic skin diseases.

Photo by Erwin Voortman on Unsplash