Imagine a disease that slowly turns the muscles, tendons and ligaments in your body to bone, restricting your ability to move, speak, eat and breathe. It sounds like something unnatural or unreal, but while very rare, such a disease actually does exist. It’s called fibrodysplasia ossificans progressiva (FOP), or as it was previously known, stone-man syndrome. For the approximately 2,500 people worldwide who suffer from it, there is no known cure. Not even surgery can correct it as tissue damage and injury from surgery trigger the disease to progress faster. Perhaps most tragic of all is that the majority of those who suffer from FOP are children, many of whom face having their lives cut short by the disease.
Dr. Clarissa Desjardins knows the stakes and she is hopeful that her company, Montréal- based Clementia Pharmaceuticals, is on the right course to finding a potential treatment. It comes in the form of a repurposed drug
called palovarotene. The compound, prior to its acquisition by Clementia in 2013, had been previously investigated as a possible treatment for emphysema or chronic obstructive pulmonary disease (COPD) by Roche Pharmaceuticals.
“It (Palovarotene) belongs to a class of drugs called retinoic acid receptor gamma (RARγ) agonists and what makes it unique is that it selectively targets a pathway involved in cartilage and bone formation,” explains Desjardins. This is important she adds, as the new bone that occurs in FOP appears first as cartilage before becoming fully mature bone.
“The idea is if you can prevent the cartilage formation, you can prevent the growth of new bone,” she says.
Breaking it down further, Desjardins states that in people with FOP, the receptors (the ACRV1/ALK2) that are involved in the bone morphogenetic protein pathway become overactive, which is why there is heterotopic ossification. In animal studies led by Drs. Maurizio Pacifici and Masahiro Iwamoto, Palovarotene was shown to stop this error message at its pathway source. Their published results were the reason that Clementia licensed palovarotene and established it as its flagship product.
“Prior to acquiring it, we were working with Roche on completely unrelated projects in personalized medicine when one of their senior executives basically pointed out this Nature Medicine paper published by scientists (Drs. Pacifici and Iwamoto) at Thomas Jefferson University on palovarotene,” she recalls. “They said look at what these scientists have discovered, this drug that was in clinical trials for lung disease and was halted actually inhibits
new bone formation in mouse models.”
Knowing her past track record for starting biotech companies including Advanced Bioconcept and Caprion Pharmaceuticals, they suggested to Desjardins that she should create a company to take palovarotene back into the clinic.
“So I did, and we called it Clementia, derived from the Latin word for compassion or empathy.”
For Desjardins, the timing couldn’t have been more right. She says that a part of her was always searching for that next great opportunity.
“It’s what I’ve loved most about leading a biotechnology company. Everything makes a difference. Given the heroic fight of these individuals affected by FOP and the fact that no one has ever developed a drug for them, launching Clementia was an easy choice to make.”
In a short time, Clementia has continued to progress rapidly with the drug and the company is currently conducting Phase 2 and Natural History clinical trials at seven international sites. The trials include both adults and children with FOP.
“We are at the exploratory stage of clinical development now,” says Desjardins, “so we are testing a lot of different things like dose, duration of treatment, and timing of assessment, all of which are designed to inform a registrational trial.”
In late February the company hit a significant milestone with the trial, announcing that the 40th and last study participant had enrolled. According to Desjardins, the success of hitting this milestone was due in large part to Clementia’s ability to work hand-in-hand with the FOP community.
“FOP patient organizations and medical experts have been very supportive in their efforts to increase awareness of our trials, and we have a fantastic clinical operations team that organizes patient travel from around the globe to our seven clinical trial sites,” she says.
Clementia has also made significant headway on the regulatory front, which has helped to further facilitate clinical development of the drug. For example, in 2014 palovarotene received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and Orphan Medicinal Product Designation from the European Medicines Agency (EMA). Additionally, the FDA also gave the drug Fast Track designation.
Financially, Clementia is very healthy as well. The company has raised US$92.5 million over the last two years, most of which came from a US$60 million mezzanine financing completed last June. The latter transaction represented the largest venture capital deal involving a biopharmaceutical company in Canada last year. It’s a tell-tale sign that investors are taking notice of palovarotene’s promise.
“Once you learn about FOP, it is impossible to forget. So a lot of people, including investors, are excited to help these individuals and are committed to rapidly vetting palovarotene in a robust development program for this overwhelming condition.”
With sufficient resources to get Clementia through to the next stage and with the Phase 2 trial now completely enrolled, Desjardins says she is hopeful that results for the Phase 2 trial could be reported by year end.
“Our next step is to incorporate the learnings of the Phase 2 and natural history studies into the design of a registrational trial and move us closer to our goal of providing a much-needed treatment for people in desperate need of one.”