I have covered Albireo Pharma (NASDAQ: ALBO:) about four years ago. At the time, Albireo was a little-known liver disease company with a promising pipeline. Odevixibat, also known as A4250, was then undergoing a Phase 3 trial in PFIC, or Progressive Familial. Intrahepatic cholestasis. It is a liver disease caused by cholestasis, where the formation of bile is impaired, leading to liver collapse. I covered the science in my previous article and it is still relevant. It is important to understand the mechanism of action of odevixibat, which is agnostic of which specific cholestatic disease it is targeting. There are many of them, and because odevixibat modulates the IBAT, or bile acid transporter, which is responsible for the circulation of bile to the liver, it can address a number of related diseases.
Several of these diseases are now in Albireo’s pipeline. Odevixibat is now approved for PFIC and is known as Bylvay. My interest in Albireo is now tied to the rest of the pipeline, which looks like this:
Phase 3 indications are Alagille syndrome and biliary atresia, which are also cholestasis-mediated diseases. Thus, the PFIC approval acts as a large proof-of-concept for these other indications, teasing out the asset.
Albireo has done Phase 1/2 work on Alagille syndrome. This was a basket trial with other diseases, including the one where odevixibat was approved. ALGS is actually a larger market than PFIC, ranging from 1/30,000 to 1/50,000 live births, compared to the latter’s 1/50,000 to 1/100,000 live births. There is currently no approved treatment for ALGS and “may include the inappropriate use of ursodeoxycholic acid (UDCA) to increase bile flow and reduce liver damage.” In addition to bile duct diversion and liver transplant surgery, other drug options, although not always effective, include:
Other drugs used for pruritus37 include cholestyramine, which sequesters bile acids in a resin complex for excretion38; rifampin, which activates the nuclear pregnane X receptor and is believed to increase bilirubin excretion and enhance enzymatic reactions that make bile acids more hydrophilic and less toxic39-41; naltrexone, an opioid antagonist used to reduce opioid-mediated neurotransmission associated with pruritus and/or cholestasis42; or antihistamines. In addition, a high-calorie diet with vitamin/mineral supplementation (eg, calcium, zinc, and vitamins A, D, E, and K) is often prescribed to provide nutritional support.43 However, these approaches may not be fully effective, and many patients either do not respond at all or require combination therapy.
Mirum Pharma’s ( MIRM ) IBAT inhibitor maralixibat was recently approved (September 2021) for cholestatic pruritus in people 1 year and older with Alagille syndrome.
In an open-label phase 2 trial of odevixibat in ALGS patients, the following data were observed:
No serious adverse events occurred and all participants completed the trial as per protocol. At the end of the multiple-escalating dose study, plasma total bile acids and FGF19 were decreased by 47% and 76%, respectively, at 3 mg/d ( P < 0.01) and by 15% and 16%, respectively. 1.5 mg twice daily (P < 0.05). Plasma C4 and fecal bile acids increased at all dose regimens by 555%, 664%, 292% and 338%, 421%, 420%, respectively (P < 0.01-0.05). The primary bile acids cholic and chenodeoxycholic acids accounted for the majority of faecal bile acids in the A4250-treated groups.
The company recently (October 2022) published top-line data from the Phase 3 ASSERT study of odevixibat at ALGS. This was a 24-week study of 52 patients comparing odevixibat and placebo in 35 and 17 patients, respectively. There were no treatment interruptions. The primary measure was pruritus, with a 1.69-point reduction in pruritus in the drug group versus 0.8 points between the drug and placebo, respectively. For the key secondary measure, serum bile acid, there was a 90-point reduction in the drug arm compared with a 22-point increase in the placebo arm. Improvements in both outcome measures were highly statistically significant. These results were actually slightly better than those of the established indications study.
The company planned to complete regulatory filings in Q1 2023. On December 19, the company announced that they have already submitted sNDAs in both the US and the EU. Expect confirmation in the first half of 2024 at the latest. They are also running the phase 3 BOLD study of biliary atresia, which is now fully enrolled. Expect approval in late 2024 if the data is good, which it likely will be given the similarities in disease and drug mechanisms for each of the three indications.
ALBO has a market cap of $408 million, a cash balance of $275 million, and the company earned $10 million in revenue this quarter. Research and development expenses for the three months ended September 30, 2022 were $23.3 million and selling, general and administrative expenses were $20.6 million. At that rate, the company has a 6-7 quarter cash flow runway, which should be enough to cover the top line timeline of the BOLD pilot data readout.
ALBO has one approved indication and label expansion in the next two years. It has two other assets (which I have not covered) in liver diseases as well. Established products generate revenue slowly but steadily. Their cash balance is decent. Despite all this, the stock is trading near 52-week lows. This can provide an opportunity, albeit in small doses.
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