Astellas Is Looking For Bolt-On Deals
Astellas Pharma is looking to add new assets to its pipeline that could launch in the late 2020s or early in the next decade, chief strategy officer Adam Pearson said in an interview, as its big-selling cancer drug Xtandi (enzalutamide) nears patent expiration in the US in 2027.
“As [Xtandi] loses sales post-LOE, it’s a big gap to fill,” Pearson told Scrip. While the company has newer drugs like Izervay (avacincaptad pegol) for geographic atrophy, Veozah (fezolinetant) for hot flashes and cancer drug Vyloy (zolbetuximab) that it expects to help fill the gap, it will also rely on business development to add sales in the latter half of the decade.
“The Iveric Bio deal, which brought Izervay, was $6bn, and we won’t be able to do anything like that in the near-term until we pay down the debt and so on, but small bolt-on deals are definitely possible,” Pearson said.
Astellas will continue to build on therapeutic areas of focus. “We’re in oncology, both immuno-oncology and targeted protein degradation, and we’re also now very much in ophthalmology … and then we have gene therapies in the pipeline, but not yet on the market,” he said. “So, I think business development will be focused around those.”
The sweet spot would be a deal in Phase I or proof of concept, but earlier-stage deals will also be important to support R&D.
“I think really good quality assets are quite hard to find. There’s a lot of competition sometimes for those,” Pearson said. “At the same time, we have a huge number of opportunities to look at. We have a huge number of companies approaching us.”
Madrigal: MASH Launch Metrics Track With Previous Blockbusters
Madrigal’s Rezdiffra (resmetirom) continues to perform well based on preliminary fourth quarter and full year 2024 sales numbers released at the start of J.P. Morgan, and CEO Bill Sibold told the meeting that the company’s internal metrics indicate the MASH drug is on a track similar to other recent specialty product launches that led to blockbuster sales.
“We benchmark ourselves against a series of launches in the last 10 years,” the exec said on 15 January. “It’s about 10 products that have launched in the specialty space. All these products are blockbusters, and many of them are becoming household names. And, as we look across all of our key performance metrics, we are tracking exceptionally well with them.”
Rezdiffra became the first approved drug therapy for metabolic dysfunction-associated steatohepatitis (also known as non-alcoholic steatohepatitis, NASH) last March, and early launch numbers in the US have gotten plaudits from market analysts. On 14 January, Wolfe Research analyst Andy Chen said, “Madrigal is meticulously executing on a thoughtful plan: a well-designed pricing and supply chain strategy, on top of optimal messaging to make all stakeholders happy, with a premeditated plan of attack against future competition.”
Madrigal estimated its fourth quarter sales of Rezdiffra at $100m-$103m, sequential growth ranging from 61%-66%, and full year sales revenue of $177m-$180m. More than 11,800 US patients had started MASH therapy on the drug by the end of 2024, the company noted. With $931m in cash on hand entering the new year, the company is gearing up for a European Medicines Agency approval decision expected in mid-2025, with plans to launch the drug itself if approved, beginning in Germany.
Sibold did not feign modesty in describing the initial months of Rezdiffra’s launch, pointing out that Madrigal needed to build a market from scratch for MASH therapy. “The launch has been incredibly successful,” he said. “We’ve secured Rezdiffra’s position as a foundational medicine in MASH, and this is an area which is continuing to get increased interest, and we expect that we are going to be the leader for many years to come.”
H.C. Wainwright analyst Ed Arce shared that optimism in a 14 January note, saying the new sales figures released by Madrigal led him to increase his 2025 sales projections from about $370m to nearly $564m. Wainwright estimates that Rezdiffra will hit its sales peak in 2032 in fibrotic MASH (F2/F3 fibrosis scores) patients with $5.5bn in revenue, and in cirrhotic MASH (F4) patients with $2.3bn in 2033.
Ultragenyx Gearing Up For A Catalyst-Rich Year
Rare disease specialist Ultragenyx has several major milestones ahead in 2025 that could give the company two new product approvals and a new drug submission by the end of the year, plus multiple Phase III clinical trial readouts.
Scrip caught up with Ultragenyx chief medical officer Eric Crombez at the J.P. Morgan meeting after the company announced its 2025 financial guidance and outlined its expected R&D pipeline milestones on 12 January and presented its case to investors on 13 January.
Ultragenyx reported that a biologics license application (BLA) for the gene therapy UX111 in the treatment of Sanfilippo syndrome type A (MPS IIIA) has been submitted to the US Food and Drug Administration and the company plans to submit a BLA for the gene therapy DTX401 for glycogen storage disease type Ia (GSDIa) in mid-2025.
The company kicked off its Phase III trial of GTX-102, an antisense oligonucleotide for Angelman syndrome, in December and expects to complete enrollment in the second half of 2025. The first interim analysis (IA1) in the Phase III Orbit study of UX143 (setrusumab), a monoclonal antibody for osteogenesis imperfecta (OI), was completed and a determination was made to continue to the second interim analysis (IA2) in mid-2025, with a potential final analysis in the fourth quarter.
“If we hit on IA2 for osteogenesis imperfecta, that will also file by the end of the year,” Crombez said. “So, great work in ’24 and then a lot of milestones coming up. … For a long time it felt like all those big stars of approvals were in the distance, and we finally have gotten into where they’re much more near-term, which is great."
Also in the pipeline, the gene therapy UX701 for Wilson disease is in stage 1 of a Phase I/II/III study and the gene therapy DTX301 for ornithine transcarbamylase deficiency in is Phase III with enrollment completion expected in early 2025.
As for moving additional assets into the clinic, Crombez said Ultragenyx needs to clear multiple pending product approvals before the company can consider advancing some of its stockpiled preclinical programs.
“We’ve had a very, very full pipeline. In my seven-year tenure, we have not had one single thing fall out of the [clinical-stage] pipeline,” he said. “To manage our spend, we’ve been really letting programs that have been coming through our translational group get to [investigational new drug (IND) application-stage], but we’re pausing them there, because once you get into the clinic, it’s just so expensive, you need to really execute against that. So, we’ve been having some pile-up at the pre-IND level, and as soon as we get some approvals, we’ll be ready to pull those in.”
Ultragenyx reported $555m-$560m in full-year 2024 revenue and forecast $640m-$670m in revenue for 2025 from its approved products.
Acadia Begins Geographic Expansion
Acadia Pharmaceuticals is making its first expansion outside of the US with the expected launch of Daybue (trofinetide) for Rett syndrome in Canada and Europe. The company announced that a marketing authorization application for the rare disease drug has been filed in Europe and a launch in Canada is planned this year, where the drug already is approved.
Expansion into Europe could more than double the size of the commercial opportunity for Daybue. About 6,000-9,000 people in the US are estimated to have Rhett syndrome versus 9,000-12,000 in the EU. Diagnosis is lower, however, for the neurodevelopmental disease, which previously had no approved therapy. Daybue was approved by the US FDA in March 2023.
“About 5,800 are diagnosed right now, and we’ve seen that increase by 20% since the launch of Daybue, so we expect a similar kind of dynamic in Europe,” CEO Catherine Owen Adams said in an interview.
Acadia will launch Daybue in Europe independently as it begins to build a global rare disease commercial team. While the company has no plans to bring its biggest selling drug, Nuplazid (pimavanserin), to Europe, the company does hope to eventually launch its rare disease pipeline drug ACP-101 for the treatment of hyperphagia in Prader-Willi syndrome in Europe.
The initial launch of Daybue got off to a strong start. The drug generated $251.7m in the first nine months of 2024. But despite the strong initial uptake, some patients fell off treatment in the first few months due to the side effect profile, which includes a harsh tolerability profile due to diarrhea.
“What we’ve learned in the last 18 months is that we need to really focus on the first few months of therapy for our patients and families,” Adams said. “What I’m putting in place for 2025 is really an enhancement to our field force.” The company is expanding its field force by about 30% to better facilitate discussions with physicians and patients about managing the side-effect profile through the first few months of treatment until patients adjust.
“What we’re finding is once the patients are through those first three or four months is that we’re getting a very strong persistency rate on Daybue,” she added. At 10 months, about 66% of patients are still on the drug.
Verve Anticipates ‘Breakthrough’ Readouts In 2025
Verve Therapeutics pre-announced its anticipated 2025 R&D milestones ahead of a 15 January presentation at the J.P. Morgan meeting, noting that the company will report initial Phase Ib results from the Heart-2 clinical trial of VERVE-102, its base editor targeting PCSK9 to treat adults with heterozygous familial hypercholesterolemia (HeFH) and adults with premature coronary artery disease (CAD), during the first half of this year. Final dose-escalation data from Heart-02 are due in the second half of 2025 and Lilly will make a decision to opt in on later stages of development of VERVE-102 also in the latter half of this year.
Scrip spoke with Verve CEO Sekar Kathiresan at J.P. Morgan about how far the company is able to get with its current cash balance, which was $539.9m at the end of September.
“Our runway goes to the middle of ’27, so that’ll allow us to get through the Phase I here for PCSK9, but also probably a Phase II, and then also the Phase I for the ANGPTL3 program,” Kathiresan said.
Verve enrolled the first patient in November in the Phase Ib Pulse-01 trial of VERVE-201, its in vivo base editor targeting ANGPTL3 in adults with refractory hypercholesterolemia who require additional lowering of LDL cholesterol despite treatment with maximally tolerated standard-of-care therapies, potentially including PCSK9 inhibitors. The company will provide an update on the study during the second half of 2025.
“We have a good setup in terms of being able to get through important value-inflection points with this current cash runway,” Kathiresan said. “This is our seventh year, and it really is shaping up to be a breakthrough year, being able to really show the world that, hey, we have a drug here with ‘102, so that’s what we’re hoping to accomplish.”
The company also nominated an in vivo gene editor, VERVE-301, which is designed to permanently turn off the LPA gene in the liver to reduce blood lipoprotein(a) [Lp(a)] levels. All three of the Verve programs fall under the company’s collaboration with Lilly.
BizDev Is A Big Deal For Agios In 2025
As Agios Pharmaceuticals’ Pyrukynd (mitapivat) enters its fourth year on the market for pyruvate kinase (PK) deficiency, the biotech is eyeing what it calls a multibillion-dollar market opportunity with potential US Food and Drug Administration approval by the end of the year for both transfusion-dependent and non-transfusion-dependent alpha- and beta-thalassemia, as well as potential launch for sickle cell disease (SCD) in 2026.
Evaluate Pharma projects worldwide sales for Pyrukynd of $101m in 2025, steadily climbing to $956m in 2030.
“Looking ahead to 2025 and beyond, we believe have a rare – pun intended – [and] distinct blueprint for success,” Agios CEO Brian Goff said in the company’s 15 January presentation at J.P. Morgan.
Additionally, Goff pointed to what he called Agios’s “very strong balance sheet,” which at the end of September 2024 included cash, cash equivalents and marketable securities of $1.7bn and enables the company to “look organically at how we can further our development of our pipeline as well as in a very disciplined way, seek external [business development] opportunities as well,” he said.
Indeed, chief financial officer Cecilia Jones affirmed that business development will be a priority for Agios in 2025, or rather that it has been for a while and that has not changed.
In particular, Jones said, the company is interested in something in the rare disease space, but not ultra-rare, and that is transformative for patients. In other words, “something that we can easily or early de-risk for regulatory approval, and obviously value-creating,” she said. “We continue to look at opportunities across the board.”
She added that the company is “not under a gun” or “desperate,” reiterating that it can do business development in a very disciplined manner.
Tris Pharma Assesses Funding Options To Accelerate Programs
Tris Pharma plans to report results in the first quarter of 2025 from the Phase III ALEVIATE-1 and ALEVIATE-2 clinical trials of cebranopadol – a dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist, also known as a dual NMR agonist – for moderate-to-severe acute pain. The two registrational trials are enrolled with more than 500 patients in the US who underwent abdominoplasty and bunionectomy, respectively.
While the private company has funded cebranopadol development on its own up to this point, brand division president James Hackworth told Scrip in an interview at J.P. Morgan that Tris is talking to investors and potential partners about options for additional funding that could further accelerate the novel pain drug’s development. And, he noted, the potential US Food and Drug Administration approval of Vertex Pharmaceuticals’ NaV1.7 inhibitor suzetrigine for acute pain later this month has helped boost interest in cebranopadol.
“It’s clear that the interest in the pain space has changed a lot over the last couple of years,” Hackworth said. “When I started working on cebranopadol five years ago, it was hard to get an investor to even talk about pain. … And now, I’m sure partly because of Vertex’s success, partly because of some of the results we’ve shown and other companies that are working and showing some interesting results at earlier stages, the investor community seems to be much more open to opportunities in pain … and believing there’s a real market opportunity.”
Tris is developing cebranopadol in chronic pain as well as in acute pain, with plans to conduct Phase II trials against active comparators in indications such as chronic low back pain, chronic osteoarthritis pain, chronic diabetic peripheral neuropathy and cancer pain. The company expects to initiate the first of those studies this year, based on feedback from the FDA.
“We’re not in a position where we’re stymied if we don’t have external funding,” Hackworth explained. “It’s more about the speed we can do everything. We’d like to do all of this in parallel, we’d like to start multiple chronic studies, launch the right way in acute, and potentially outside financial partners could help us do more things in parallel and accelerate things.”
