In an era of cancer moonshots, researchers are aiming high in hopes of finding a cure, or at least transforming cancer into a chronic condition. Amid these lofty goals, however, there are a number of related medical needs which have gone unnoticed. Stockholm-based PledPharma has set its sights on addressing chemotherapy induced peripheral neuropathy (CIPN), a condition experienced by more than 50% of all cancer patients.
The condition affects cancer patients who are treated with many of the foundational therapies used to treat solid-organ cancers, including oxiplatin, cisplatin, carboplatin, paclitaxel and docetaxel.
“There is a huge unmet need associated with CIPN, and no approved treatments,” said PledPharma CEO Jacques Näsström. “We are in phase 2b development of PledOx for treatment of CIPN in order to address this need.”
Näsström estimates 1.7 million patients suffering from CIPN across the U.S., Europe, and Japan could benefit from PledOx—a sizable and potentially remunerative market.
An unmet, and underappreciated, medical need
Neuropathic pain may not seem like a big deal compared to the weighty diagnosis of cancer. But it has serious short- and long-term consequences. CIPN can compromise patients’ ability to complete their chemotherapeutic regimens. It also has a detrimental effect on quality-of-life (QOL).
According to Näsström, “the main symptoms are tingling, numbness, a ‘pins and needles’ feeling and often the sensation of pain. Patients develop problems with balance and find it difficult to work. Even worse, symptoms can last for more than a decade post-treatment---even when the cancer is cured.”
CIPN is not the only negative side-effect associated with chemotherapy. Thrombocytopenia and neutropenia are also common side effects. For these conditions, however, limited treatment options already exist.
“CIPN is the most severe side effect of chemotherapy,” said Näsström. "Doctors try to address CIPN with off-label treatments such as antidepressants and drugs like pregabalin, but these treatments have been shown not to work.”
PledOx works by mimicking cellular regulation of an enzymatic pathway tied to oxidative stress. In doing so, it protects cells from oxidative stress and prevents cell death.
Like many drugs, PledOx was discovered serendipitously.
Pledox is derived from a MRI contrast imaging agent known as mangafodipir, which was originally marketed by Nycomed Imaging before that company was bought by GE. In the 1990s, Nycomed researchers discovered mangafodipir had the ability to prevent oxidative stress, but therapeutic applications were not pursued at first.
PledPharma licensed the IP for mangafodipir in 2007, one year after the company’s founding. The company has also been granted a composition of matter patent, which is effective through 2032.
In a phase 2b study, 173 colorectal cancer patients received a 5 mg injection of PledOX right before each chemotherapy treatment. PledOx significantly reduced the incidence neuropathy and the time-to-onset in patients undergoing an eight-cycle chemotherapy regimen. This is “groundbreaking” data, according to Näsström, and it captured the attention of potential partners during meetings at BIO Spring last week.
The most expedient route to market
Similarly to other European companies, PledPharma has had the U.S. in mind from the beginning.
“Our goal is to find the right partner for further development and ultimately commercialization. The US is an extremely important market—and there are a lot of potential partners in the US. In order to get PledOx to market as quickly as possible, out-licensing is the best strategy,” Näsström said.
PledPharma has done a lot of the upfront legwork to pave the way for PledOx’s approval. Their strategy has been built around early consultations with regulatory authorities in both Sweden and the US, including a meeting with the FDA before the company opened its investigational new drug application in 2012.
“We had an end-of-phase-2 meeting with the FDA in November 2015 and received clear guidance on continued development,” Näsström said.
As PledOx moves towards phase 3, the FDA is looking for more data focusing on patient experience—a key metric in a condition without clear biological signs.
“Cancer trials are long,” Näsström explained. “It takes a year just to recruit. The FDA has requested two phase 3 trials, including a trial in which the primary endpoint is based on patient-reported outcomes at three months post-treatment. There are no biomarkers for neuropathy. The patient’s experience is the best guide.”
The FDA has also requested a non-inferiority trial to make sure that treatment with PledOx does not interfere with chemotherapy treatment.
Looking ahead toward patient access, Näsström is confident that the conversation with payers will be straightforward. The lack of other approved treatment options in this space should help PledOx win reimbursement from payers.
But despite the promise of PledOx, Näsström does not foresee an era in which chemotherapy will no longer be part of the medical toolkit.
“Chemotherapy is here to stay. There haven’t been any new therapies for certain cancers, though there is potential for some new combination therapies,” he said. “Our goal is to help relieve patients of one of the worst side effects of chemotherapy, so they can focus on their treatment.”