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With the flurry of news from earnings week(s), we've captured a few tidbits to share. Notably some updates on Alzheimer's, Oncology, and Obesity, including M&A updates and thoughts on Patent Cliffs.
Alzheimer's News
AbbVie discontinues its mid-stage Alzheimer’s program due to a failure to differentiate. ABBV-19, a monoclonal antibody engineered to eliminate amyloid plaque, similar to Eli Lilly’s donanemab, is leaving the company’s monotherapy pipeline as a standalone antibody due to differential insufficiency compared to other upcoming treatments.
In 2022, ABBV-916 started clinical trials in a phase 1/2 trial that progressed to a phase 2 trial, with ongoing recruitment as of June 7. The goal was to evaluate the safety and effectiveness of the mAb in treating early-stage Alzheimer's disease in an anticipated 195 individuals. A proof-of-concept section and a multiple ascending dose component were included in the two-stage study, with an estimated 2031 completion date. According to a spokesman, the company plans to consider options such as combination techniques for the asset.
Eli Lilly's donanemab, also marketed as Kisunla, was approved in early July for patients with early onset Alzheimer's disease. The indication for Kisunla is almost the same as the one for Eisai / Biogen's Leqembi, which received complete approval by the FDA in July 2023. Before beginning treatment, both medications require confirmation of amyloid beta pathology in patients' brain tissue. Additionally, a boxed warning about the possibility of amyloid-related imaging abnormalities—known adverse effects for those antibodies—is included with both medications. Lilly claims that Kisunla is the first anti-amyloid medication that permits patients to discontinue treatment once amyloid plaques are eliminated, meaning fewer infusions and reduced treatment expenses.
Despite giving up on ABBV-19, AbbVie remains heavily involved in neuroscience with its $8.7 billion acquisition of Cerevel Therapeutics, which is anticipated to close in August. Emraclidine, a muscarinic M4 selective positive allosteric modulator being investigated in schizophrenia and Alzheimer's psychosis, is the star of Cerevel's pipeline. Regarding the company's broader pipeline strategy, it plans to continue accumulating assets, particularly through early-stage acquisitions.
For more details:
Oncology News
Three months after receiving an expedited FDA approval for Ojemda, Day One Biopharmaceuticals is collaborating with another oncology expert to expand the medication's international market share. An ex-U.S. licensing deal for tovorafenib (licensed as Ojemda in the U.S.) in pediatric lo-grade glioma (pLGG) including the development of possible future indications was disclosed by Day One and Ipsen last week. Ipsen is paying approximately $111 million up front for the regulatory and marketing rights to tovorafenib outside of the United States. This includes a $40 million equity investment in Day One. Day One may receive up to $350 million in milestones and "tiered double digit royalties" depending on future success.
According to the company, pLGG sufferers have a variety of symptoms, such as fatigue, nausea, neurological issues, difficulties with speech and vision, and more. The illness may have a seriously negative effect on a child's growth and well-being. Day One's medication is competing with Novartis's combination of Tafinlar and Mekinist. In 2023, Novartis received FDA approval for treating pLGG cases containing BRAF V 600 mutations, a more limited application. Ojemda, the first commercial product from California-based Day One, is expected to reach peak sales of $750 million. Regarding Ipsen, the business's first-half sales increased by 8% on a yearly basis to $1.8 billion.
For more details:
Obesity News
Roche has achieved another early victory with its $2.7 billion wager on Carmot Therapeutics. Using Carmot's oral GLP-1 prospect for four weeks, participants in a phase 1 trial dropped 7.3% of their body weight, indicating the candidate's ability to compete with companies like Pfizer and Eli Lilly.
By purchasing Carmot, Roche gained control over an oral small molecule as well as once-weekly and once-daily GLP-1 injectables. Following up on its May phase 1 data announcement regarding an injectable GLP-1/GIP agonist, Roche has now provided an early analysis of the effectiveness of its oral counterpart, CT-996. In contrast to the placebo cohort, which resulted in a 1.2% drop in body weight after four weeks, CT-996 participants had lost an average of 7.3% of their body weight. The individuals were obese yet did not have type 2 diabetes.
The 6.1% placebo-adjusted weight loss carries a clinical significance for Roche. The figure also appears to have commercial significance. In a phase 3 trial, Novo Nordisk associated a 12.7% placebo-adjusted weight loss with its oral semaglutide formulation. However, that drop occurred 68 weeks later, and the molecule had to be taken with a sip of water and on an empty stomach. Phase 2 results showed that after 36 weeks, Lilly's orforglipron, which has easier dosage requirements, produced 12.4% placebo-adjusted weight loss.
Roche reported less weight loss, but after four weeks of treatment, CT-996 started to show improvements. After four weeks, none of the participants in Lilly's orforglipron research had lost five percent of their body weight. Cross-trial comparisons are inherently difficult due to gaps in the data provided by Roche, such as weight at baseline; however, the information that is currently available suggests CT-996 may be competitive.
Patients may use CT-996 for oral weight maintenance therapy following injectables in addition to glycaemic management and weight loss. According to a recent study, almost 85% of patients cease taking GLP-1 medications within two years and put on weight again, demonstrating the necessity for the use of maintenance therapy.
CT-996 is still being tested by Roche in the phase 1 study. The trial's second phase will involve recruiting two consecutive cohorts of thirty obese and type 2 diabetics.
For more details on GLP-1 Developments:
Patent Expiry - Analyst Views
According to analysts, a total of $183.5 billion in revenues are expected to be generated from drugs losing exclusivity through 2030; Amgen, Bristol Myers Squibb (BMS), and Merck are the companies most at risk. However, Big Pharma is thought to have $383.1 billion in negotiation power at its disposal to help minimize the impact of the Patent Cliffs. Novo Nordisk, Merck, and Johnson & Johnson are also well positioned to expand M&A efforts to minimize LOE on their key products.
Compared to the industry average of 38% of revenues at risk, J&J is performing considerably well because just 33% of its income is at risk from patent expirations through 2030. Vertex (6%), Gilead (24%), AbbVie (29%), Eli Lilly (31%) and Pfizer (33%), are also in a favourable situation with less revenue at risk fro LOE.
Amgen, whose top four products are on the clock, is at the other end of the spectrum with the greatest income at danger (67%). Over the next two years, the patents for the bone cancer medications Prolia and Xgeva, which sold a combined $6.1 billion last year, are set to expire. By the end of the decade, Enbrel ($3.7 billion) and Otezla ($2.2 billion) are also expected to lose their exclusivity. With its $27.8 billion acquisition of Horizon, which was finalised in October and brought potential blockbusters in Tepezza for thyroid eye disease, Krystexxa for gout, and Uplizna for a rare neurological ailment, Amgen has already made a significant step towards tackling their patent cliff.
BMS is the next company on the patent expiry exposure list, with 63% of its revenue at risk. Eliquis, a blood thinner that made $12.2 billion in revenue last year, and Opdivo, a cancer therapy that made $9 billion, both possess patents that will soon run out, while Revlimid, a different cancer medication that made $6.1 billion, has already lost its exclusivity in the United States. In response, BMS purchased Mirati, RayzeBio and Karuna at the end of last year.
Merck is the next company on the list, with 56% of its revenue at risk of patent expiry. The majority of its revenue comes from the $25 billion in sales of the company's blockbuster cancer medicine Keytruda, which accounted for 42% of its overall revenue last year. In 2029, Keytruda's exclusivity will end.
For more details on GLP-1 Developments:
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