Highly active antiretroviral therapies (HAART), combining multiple drugs into a cocktail, can effectively suppress HIV. But patient compliance in taking pills, especially after the virus becomes resistant and requires multiple pills per day, can be a challenge.
Citing a study by Sharon Mannheimer of Columbia University Medical Center, Nader Pourhassan, CEO of Cytodyn Inc., told investors on a call last week that after eight months of therapy only 60 percent of patients reported 100 percent adherence to their medication.
To address the compliance issues, Cytodyn is developing PRO 140, which is injected weekly. PRO 140 is a monoclonal antibody that binds to CCR5, which the virus uses to enter T cells. The drug doesn't affect the normal function of CCR5 that helps the body to elicit an immune response. As a monoclonal antibody, PRO 140 doesn't have the same type of side effects seen with many HAART regimens.
In February last year, Cytodyn, of Vancouver, Wash., reported positive phase IIb data showing that 98 percent of the 40 patients were able to keep their virus levels down with four weeks of treatment.
While some patients failed the therapy later in the trial – 70 percent of patients passed 11 weeks of monotherapy – PRO 140 is clearly helpful for some patients. Fourteen patients entered an extension trial that has shown PRO 140 can produce a complete viral load suppression for well over a year. Some patients are approaching 17 months on the monotherapy and three patients have obtained undetectable levels of virus in their blood samples taking only PRO 140 once a week. Typically less than 40-50 viral copies per mL is considered a successful viral suppression.
Cytodyn is testing PRO 140 in a phase III trial as an adjunct to HAART in patients who have already become resistant to at least one therapy. The trial is expected to read out this year, and the company hopes to have its biologics license application filed with the FDA by November, potentially allowing commercialization of PRO 140 next year.
Pourhassan estimates there are 200,000 HIV patients who have become resistant to at least one drug, creating a $5 billion opportunity.
Because PRO 140 works through a different mechanism of action than other HAART drugs, it's possible that the adjunct treatment could delay the development of further resistance if patients accidentally skip a dose of their oral medications.
Cytodyn is also planning on running a pivotal phase III trial testing PRO 140 as a monotherapy. If successful, the data would be used as a label extension – assuming the drug is approved as an adjunct therapy first. The company is currently working out a phase III protocol to be reviewed by the FDA, but it will likely include a switch from HAART to PRO 140, demonstrating that the drug candidate can continue to suppress viral loads.
If successful, a monotherapy could attract patients that don't want to take a daily medication. "It reminds them of their HIV every day," Pourhassan said.
But he also sees a large opportunity for using the drug as a monotherapy in patients currently not taking any medication for fear of side effects from HAART regimens. The patients could take the oral medications until their viral load is suppressed and then switch to PRO 140 as a maintenance therapy. "It'll open the door for patients that are not taking anything," Pourhassan told BioWorld Insight.
EVEN LONGER ACTING
Cytodyn isn't the only company working on a long-acting injectable HIV drug. Viiv Healthcare Ltd. is working with Johnson & Johnson's Janssen Sciences Ireland UC subsidiary on a regimen that can be dosed even less frequently.
The duo is testing a combination of long-acting nanosuspension injectable versions of Viiv's cabotegravir and Janssen's rilpivirine. Both drugs also have oral versions; rilpivirine is already approved as Edurant, and Viiv is testing an oral version of cabotegravir in combination therapies.
In a phase IIb study, dubbed LATTE 2, patients who received injections of cabotegravir and rilpivirine every eight weeks over the 32-week trial had a viral suppression rate of 95 percent, comparable to the control group that saw 91 percent viral suppression after receiving a three-drug oral regimen of investigational cabotegravir and two nucleoside reverse transcriptase inhibitors. The trial also tested dosing the injectable drugs every four weeks, but it produced a similar viral suspension rate of 94 percent, comparable to the eight-week dosing.
Earlier this month, London-based Viiv and Janssen formalized their collaboration to develop the injected combination, announcing plans to start a phase III program in mid-2016.
Cytodyn's Pourhassan didn't seem worried about the competition, though, highlighting the fact that the intramuscular injections are seen as "painful" by most patients – 93 percent of injection recipients in the phase IIb trial reported it as a side effect – and pointing out that the injections are performed at the doctors' office. "We believe patients want something they can do at home," he noted of PRO 140's subcutaneous injection method. //