Allena Pharmaceuticals has quickly made the move from a discovery- to a clinical-stage company. Allena went public about eight months ago and already has a product (ALLN-177) that addresses a rare disease population and is also in a much broader, Phase 3 clinical trial. Allena is developing treatments for rare and severe metabolic disorders that impact the kidney, which the company’s president and COO, Dr. Louis Brenner, believes is an under-served area.
“I may be showing my own bias here as a kidney specialist and biotechnology executive,” says Brenner. “I believe the amount of discovery and new drug development being conducted to treat the causes of kidney failure has been relatively modest. If you look at the drugs that are marketed for kidney patients, most of them treat the complications of kidney disease, but do not specifically address the causes. Drugs that attempt to treat the causes of kidney disease are few and far between.”
Treat Both Children And Adults
Oxalate is a very small molecule (a two-carbon carboxylic acid) that is ever-present in food and in humans and is a metabolic byproduct of digestion. In most circumstances, it is handled and excreted by the kidney on a daily basis. Patients with the metabolic disorder hyperoxaluria have extremely high levels of oxalate. The disorder results in the most common form of kidney stones, and it can lead to kidney failure.
Allena is currently enrolling patients into a Phase 2 study of ALLN-177 to treat the most severe forms of hyperoxaluria associated with advanced chronic kidney disease and systemic oxalosis, a potentially fatal condition that results in oxalate crystal formation throughout the body. The orphan disease trial hopes to enroll 15 to 20 patients from two at-risk patient populations. One of those populations is individuals with the rare, orphan genetic form of disease called primary hyperoxaluria. In those patients, a genetic defect causes the liver to produce excess oxalate. Oxalate only leaves the body via the kidney, which can become overwhelmed and, ultimately, damaged. Because this is a genetic disease, it often affects children and adolescents.
The other patient population is individuals with gut diseases associated with malabsorption, known as enteric hyperoxaluria. The gut diseases include for example, Crohn’s, ulcerative colitis, cystic fibrosis, and celiac disease. This patient population also includes those undergoing GI surgery, such as gastric bypass for obesity or short bowel syndrome due to Crohn’s disease. It can also include patients treated for cancer. These patients are primarily adults.
Although Allena’s Phase 2 trial will admit both adults and minors, Brenner notes the study will focus on adolescents, not children. He believes treating adolescent patients is a necessity. If children born with the genetic disorder have a lifelong risk of kidney failure, treating them as adolescents could prevent the disease from progressing to that failure point.
Dosing Is Not A Challenge
It’s unusual to see both adults and children being treated in the same clinical study. Brenner notes this is generally the case because adults and children will require different dosing amounts. That will not be the case for Allena’s study.
“In our trial, the drug will work in the patient’s gut,” says Brenner. “The drug is not absorbed into the body. Patients will receive multiple doses of the drug each day, which are designed to break down oxalate when it enters the body with food or from pulling oxalate from the body into the gut. Because the drug is oral and non-absorbed, potential differences in pharmacology between adults and children should be less pronounced.”
Brenner adds that pharma has a long and successful history of successful gut restricted therapeutics being used to treat kidney and metabolic disease. Those therapeutics are generally polymers or resins that rely on chemistry to do the job. What’s unique about the Allena program is that its treatment is a biologic.
“We are delivering an oral form of a bacterial enzyme that works in the gut,” he says. “It’s a variation on that long-standing theme of using the gut to treat metabolic disease. That makes our program unique. There are not too many oral biologics in testing or on the market. Biologics are almost always infused or injected. ALLN-177 is manufactured the same way you would manufacture any biologic, but it’s formulated for oral use rather than injection.”
Brenner adds that because patients are receiving a biologic, they are receiving the specificity of an enzyme substrate reaction. The enzymes target a unique substrate that performs one job. Therefore, patients are not expected to experience side effects or other unintended effects from the treatment, such as unintended binding. ALLN-177 is designed to only interact with oxalate.
Stick To The Regimen
Allena’s treatment is self-administered. Patients are instructed to take the capsules with meals. However, patients are required to take the drug 5 times per day for 12 weeks in the Phase 2 study. Medicines cannot help patients if they are not taking it, and trial results can be jeopardized if patients fail to take the drug as prescribed. That might lead many clinical executives to worry about patient adherence to the dosing requirements.
“We considered that, especially with the younger patients,” says Brenner. “It is certainly a plausible question. We plan to treat adolescents, and when we do, we plan to use reminders. However, we do not expect to have compliance issues. We are dealing with a symptomatic disease. Patients will experience kidney stones, which are quite painful. They may have three or four kidney stones per year. These stones can be a painful reminder to patients that they need to take their medicine. That desire to prevent kidney stones, which can also cause kidney damage, should be a constant reminder to patients to adhere to the treatment regimen.”
Allena currently has 38 employees but Brenner notes since going public and starting late-stage clinical trials, the company has been in a rapid growth phase. Still, the company employs a virtual operating model. There is technical and clinical expertise in-house, but Allena works with contract manufacturers for drug substance and product as well as CROs for trial execution.
“We employ a specialty approach where we work with carefully chosen industry partners for manufacturing, clinical development, and lab testing,” he says. “On the manufacturing side of the house, we have chosen partners with expertise in fermenting proteins. We have developed unique technologies with these partners, that we are in the process of optimizing, to be able to formulate the proteins for oral delivery. The final product is optimized for stability at room temperature. Our manufacturing partners are in the U.S. as well as overseas.”
The company has worked with several CROs in the past, and is in the process of hiring a global CRO. The company has received orphan designation outside the U.S. and will be enrolling patients outside the country for ongoing and planned trials. Prior trials were performed exclusively in the U.S.
Allena uses a pretty standard CRO selection process. An RFP is written and made available to CROs that seem qualified to perform the trial. Those companies are brought in to make a presentation, and a CRO is chosen. Brenner prefers partners with expertise in rare and orphan diseases generally, and who understand the challenges presented by renal and metabolic disease trials.
“As a virtual company, we need that specific expertise,” says Brenner. “But it is also very important for us to be in sympatico with our key vendors. A small company will live and breathe on the basis of the relationship it has with its outsourcing partners.”