Calliditas pushing on with kidney disease drug after IPO success

Calliditas Therapeutics has just pulled off the largest biotech IPO in Europe this year and is using it to bring a drug for a rare kidney disease to market. Richard Staines caught up with CEO Renee Aguiar-Lucander to find out more.

Swedish biotech Calliditas has some grand plans for a drug to treat a rare kidney disease – after its clever approach to treating IgA using a new formulation of a known active ingredient won over investors.

Calliditas’ strategy has proved to be a winner with investors, who backed the IPO in July after seeing the potential upside of the story told by CEO Renee Aguiar-Lucander, herself a former investor who has been a partner at companies such as Omega Fund Management and 3i Group.

The Swedish biotech, formerly known as Pharmalink before a name change last year, raised more than $81 million with its IPO on the country’s NASDAQ stock exchange in July.

This provided the funding needed to take its formulation of budesonide into late stage trials for the rare disease, IgA nephropathy, also known as Berger’s disease or IgAN.

Its technology is based around a targeted approach that delivers the budesonide to a particular part of the intestine where the disease is thought to originate.

Although classified as an orphan disease, the company estimates that there are about 130,000-150,000 people in the US and about 200,000 people in Europe with the condition.

Symptoms manifest themselves in the kidney, as function progressively deteriorates as the organ becomes inflamed as a result of lodged IgA antibody complexes. These IgA antibodies are actually produced by lymph tissue known as Peyer’s patches that line the ileum region of the small intestine. In IgA nephropathy however, these antibodies have a defect and appear in the blood, which causes an autoimmune reaction which leads to the complexes being formed.

The theory is that as these IgA complexes in the blood get trapped in the kidneys, this causes inflammation and damage to the kidneys, ultimately affecting kidney function.

These IgA deposits may cause the kidneys to leak blood, and protein into the urine, and over time a significant portion of patients end up at risk of ESRD, end stage renal disease, resulting in the need for dialysis or transplantation.

Unfortunately, once the kidney is damaged, it cannot be repaired – but the hope is that by preventing Peyer’s patches from producing faulty IgA antibodies which end up in the circulation, it will be possible to prevent the disease from worsening.

Calliditas’ drug, a formulation of the established immunology drug budesonide, works by targeting these Peyer’s patches.

The drug is contained in a capsule that only dissolves when it encounters the right pH levels in the ileum and is delivered by miniature beads that allow for a sustained short release of drug.

This down-regulates the activity in the Peyer’s patches and reduces the levels of IgA in the blood, stopping the disease in its tracks.

Path to market

Aguiar-Lucander said the IPO was helped by successful phase 2b trial results, and a clear path to a regulatory filing that is based upon a scaled-up version of the mid-stage trial.

The trial is straight forward in design and is a re-run of the phase 2b 150 patient trial, expanded to 200 patients on a global basis.

It will also include an extension stage to confirm the drug’s impact on kidney function, which will read out post approval based on top-line data.

This is what makes the drug interesting from an investors’ point of view: it can be seen as relatively low-risk in the hit-and-miss field of drug development thanks to some convincing results from the previous trial, yet there are no specially approved therapies for the disease.

Aguiar-Lucander said: “Nothing is ever guaranteed but as far as possible we have tried to address the most common risks and from that perspective it is attractive in terms of risk-reward.”

Also, Calliditas noted it is the only company that has run a successful Phase 2b study in this indication where “a lot of people have tried [to develop therapies] and failed.”

Existing therapies can slow the progress of the disease in some of the patients and help patients manage symptoms such as high blood pressure, protein in the urine, and swelling in the hands and feet.

“By targeting the origin of the disease through Peyer’s patches there is potential that this could be disease modifying,” said Aguiar-Lucander.

Pricing flexibility

In terms of the sales estimates, the numbers suggest sales of more than a billion dollars annually because of the comparatively large patient groups, despite the drug’s categorisation as a rare disease.

Aguiar-Lucander said this gives the biotech some flexibility on pricing, especially if it manages to convince healthcare systems that the drug can prevent patients reaching the later stages of the diseases.

The consequences of kidney failure are a disaster for patients, but they also place a huge burden on the healthcare system providing them with dialysis, or costly transplant operations.

“There are patients that get to that stage in their forties and fifties. The quality of life issues and costs for society are therefore really quite high,” she said.

In terms of timelines, the trial will take a couple of years to recruit all its patients but read out of headline data before the end of 2020 is the target, followed by filings with regulatory agencies in 2021.

This sets up a possible launch with a conditional licence in late 2021, early 2022, with Calliditas planning to retain marketing rights in the US and partnering in other countries.

The phase 3 trial’s extension study component will provide the confirmatory data allowing for a full approval if all goes well.

Although the FDA has not granted the drug breakthrough status as it is not based on a novel active ingredient, talks have been positive so far, said Aguiar-Lucander.

“The FDA has been extremely helpful, and they are motivated by the possibility of bringing approved medicines to this patient population,” she added.