Platelets are colorless cells produced in the bone marrow that help to form blood clots in the vascular system and prevent bleeding. Thrombocytopenia is a condition in which the number of platelets circulating in the blood is lower than normal. Severe or life-threatening bleeding can occur when the patient's platelet count is moderate to severely reduced, especially during invasive surgery. Patients with significant thrombocytopenia typically receive platelet transfusion immediately prior to surgery to increase platelet count. However, platelet transfusion has a risk of infection and other adverse reactions.
Lusutrombopag of Yanyeyi
On July 31, after completing the priority review, the US FDA approved Mulpleta (Lusutrombopag) from Yanyeyi, a daily small-dose thrombopoietin (TPO) receptor agonist for oral treatment. Thrombocytopenia in adults with chronic liver disease (CLD) undergoing surgery.
Thrombocytopenia is often observed in patients with CLD, and studies have shown that it occurs in 78% of patients with cirrhosis. The thrombocytopenia associated with CLD is defined as a platelet count of less than 150,000 per microliter. CLD thrombocytopenia increases the risk of bleeding and requires repeated platelet transfusions, thereby increasing outpatient visits and hospitalizations. Patients with CLD with thrombocytopenia have a three-fold higher annual medical cost than patients with CLD without thrombocytopenia. When the platelet count is less than 50,000/μl, surgery or traumatic bleeding is exacerbated, and routine diagnostic procedures and patient care are significantly complicated. Therefore, there is an urgent need for new treatment options in this field. At the same time, adult patients with chronic liver disease often need surgery for various reasons, and can provide this new oral treatment to patients without relying on platelet transfusion.
Mulpleta (Lusutrombopag) interacts with the transmembrane domain of human TPO receptor expressed on megakaryocytes to induce proliferation and differentiation of megakaryocyte progenitor cells from hematopoietic stem cells and megakaryocytes.
The FDA approved Mulpleta based on two Phase III clinical trials (L-PLUS 1 and L-PLUS 2), and Mulletta met both primary and secondary endpoints with statistically significant results.
In September 2015, Mullleta was approved by the Japanese Ministry of Health, Labor and Welfare to improve CLD-related thrombocytopenia in patients undergoing selective invasive surgery. The European Medicines Agency has also verified the application of the lusutrombopag standard marketing authorization application for Yan Yeyi, which is expected to be approved in the first half of 2019.
In the United States, Mulpleta is expected to be available in early September 2018.
Avatrombopa of AkaRx
On May 21, Dovaex (Avatrombopag) of Dova's AkaRx company received FDA approval for the treatment of chronic liver disease in adults undergoing dental or other surgery for low thrombocytopenia. It is the first drug approved by the FDA for this purpose.
The safety and efficacy of Doptelet was studied in two trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who plan to receive a platelet transfusion that usually requires surgery. Two dose levels of Doptelet administered orally within 5 days compared to placebo (untreated) were tested. The results of the trial showed that for the two dose levels of Doptelet, the platelet count was increased in a higher proportion of patients, and platelet transfusion or any salvage therapy was not required on the day of surgery and within 7 days after surgery.
Received market attention
Both Mulpleta and Doptelet have an urgent market demand and are receiving attention.
Mulpleta of Yanyeyi and Doptelet of AkaRx are very similar in terms of safety, efficacy and ease of administration. Yan Yeyi won the FDA's approval of Mullleta, but AkaRx's Doptelet was approved in the US two months earlier than Mullleta, and it is foreseeable that the competition between the two will be fierce.
Some analysts said that the degree of competition will depend on market access and pricing strategies. Mulpleta (lusutrombopag) of Yanyeyi has been approved in Japan and has two clinical studies to prove its case. In both trials, 78% and 65% of patients did not require platelet transfusion before surgery, compared with 13% and 29% of the placebo group.
Compared with Doptelet, although Mulpleta has a lower clinical response rate, Leerink analyst Geoffrey Porges pointed out that the limit of Yan Yeyi is strict. Therefore, he believes that the two drugs "do not seem to have a difference in efficacy."
Both drugs have their own advantages in terms of ease of administration. Unlike the complex dosing regimen used in some clinical trials, Mullletta's instructions indicate that it uses a fixed dose of 7 days, which is longer than the standard required by Doptelet for 5 days.
However, as Evercore ISI analysts Jon Miller and Umer Raffat point out, Mullleta can start 8 to 14 days before scheduled surgery, while Doptelet's window is relatively narrow in 10 to 13 days. Mulpleta's wider time window may make the surgery plan easier to arrange. In addition, the patient can be dosed close to the date of the scheduled surgery, and if the cytopenia problem occurs during this process, the administration is easier.
Because the characteristics of the two drugs are very similar, both the Leerink and Evercore teams believe that the pricing strategy will be a key factor in the gap between the two drugs.
Yan Yeyi has not announced its price or release schedule. Dova's AkaRx has announced that Doptelet's 40 mg tablet is priced at $9,000 and 60 mg is $13,500, which is higher than Leerink's previous forecast of $6,000. Some analysts expressed concerns about their high prices. It is difficult to predict how responders (medical insurance agencies) respond to this pricing policy, and in many cases, the cost is even higher than surgery. To ensure successful sales, both Dova and Yan Yeyi have developed a reimbursement support program and set up a team with experience in sales of liver disease.
There is also an urgent need for such drugs in the country. It is known that on March 19 this year, Fosun Pharma and AkaRx reached an agreement on Avatrombopag to obtain an exclusive license for the development and sale of the drug in mainland China and Hong Kong. Under the agreement, Fosun Pharma will assist AkaRx in developing Avatrombopag in China and Hong Kong to treat thrombocytopenia in patients with chronic liver disease and will support its development for other indications. Avatrombopag has been approved for chronic liver disease-related thrombocytopenia, and it is also undergoing chemotherapy-induced thrombocytopenia and chronic idiopathic thrombocytopenic purpura. In addition to being approved for chronic liver disease thrombocytopenia, Mulpleta is also being used clinically for immune thrombocytopenia.
According to the survey, the basic patent of Avattombopag will expire in 2023. The Lusutrombopag patent claimed by Yanyeyi Company is more complicated, and it receives multiple patent protections, and it will take some time to expire.
Lusutrombopag of Yanyeyi
On July 31, after completing the priority review, the US FDA approved Mulpleta (Lusutrombopag) from Yanyeyi, a daily small-dose thrombopoietin (TPO) receptor agonist for oral treatment. Thrombocytopenia in adults with chronic liver disease (CLD) undergoing surgery.
Thrombocytopenia is often observed in patients with CLD, and studies have shown that it occurs in 78% of patients with cirrhosis. The thrombocytopenia associated with CLD is defined as a platelet count of less than 150,000 per microliter. CLD thrombocytopenia increases the risk of bleeding and requires repeated platelet transfusions, thereby increasing outpatient visits and hospitalizations. Patients with CLD with thrombocytopenia have a three-fold higher annual medical cost than patients with CLD without thrombocytopenia. When the platelet count is less than 50,000/μl, surgery or traumatic bleeding is exacerbated, and routine diagnostic procedures and patient care are significantly complicated. Therefore, there is an urgent need for new treatment options in this field. At the same time, adult patients with chronic liver disease often need surgery for various reasons, and can provide this new oral treatment to patients without relying on platelet transfusion.
Mulpleta (Lusutrombopag) interacts with the transmembrane domain of human TPO receptor expressed on megakaryocytes to induce proliferation and differentiation of megakaryocyte progenitor cells from hematopoietic stem cells and megakaryocytes.
The FDA approved Mulpleta based on two Phase III clinical trials (L-PLUS 1 and L-PLUS 2), and Mulletta met both primary and secondary endpoints with statistically significant results.
In September 2015, Mullleta was approved by the Japanese Ministry of Health, Labor and Welfare to improve CLD-related thrombocytopenia in patients undergoing selective invasive surgery. The European Medicines Agency has also verified the application of the lusutrombopag standard marketing authorization application for Yan Yeyi, which is expected to be approved in the first half of 2019.
In the United States, Mulpleta is expected to be available in early September 2018.
Avatrombopa of AkaRx
On May 21, Dovaex (Avatrombopag) of Dova's AkaRx company received FDA approval for the treatment of chronic liver disease in adults undergoing dental or other surgery for low thrombocytopenia. It is the first drug approved by the FDA for this purpose.
The safety and efficacy of Doptelet was studied in two trials (ADAPT-1 and ADAPT-2) involving 435 patients with chronic liver disease and severe thrombocytopenia who plan to receive a platelet transfusion that usually requires surgery. Two dose levels of Doptelet administered orally within 5 days compared to placebo (untreated) were tested. The results of the trial showed that for the two dose levels of Doptelet, the platelet count was increased in a higher proportion of patients, and platelet transfusion or any salvage therapy was not required on the day of surgery and within 7 days after surgery.
Received market attention
Both Mulpleta and Doptelet have an urgent market demand and are receiving attention.
Mulpleta of Yanyeyi and Doptelet of AkaRx are very similar in terms of safety, efficacy and ease of administration. Yan Yeyi won the FDA's approval of Mullleta, but AkaRx's Doptelet was approved in the US two months earlier than Mullleta, and it is foreseeable that the competition between the two will be fierce.
Some analysts said that the degree of competition will depend on market access and pricing strategies. Mulpleta (lusutrombopag) of Yanyeyi has been approved in Japan and has two clinical studies to prove its case. In both trials, 78% and 65% of patients did not require platelet transfusion before surgery, compared with 13% and 29% of the placebo group.
Compared with Doptelet, although Mulpleta has a lower clinical response rate, Leerink analyst Geoffrey Porges pointed out that the limit of Yan Yeyi is strict. Therefore, he believes that the two drugs "do not seem to have a difference in efficacy."
Both drugs have their own advantages in terms of ease of administration. Unlike the complex dosing regimen used in some clinical trials, Mullletta's instructions indicate that it uses a fixed dose of 7 days, which is longer than the standard required by Doptelet for 5 days.
However, as Evercore ISI analysts Jon Miller and Umer Raffat point out, Mullleta can start 8 to 14 days before scheduled surgery, while Doptelet's window is relatively narrow in 10 to 13 days. Mulpleta's wider time window may make the surgery plan easier to arrange. In addition, the patient can be dosed close to the date of the scheduled surgery, and if the cytopenia problem occurs during this process, the administration is easier.
Because the characteristics of the two drugs are very similar, both the Leerink and Evercore teams believe that the pricing strategy will be a key factor in the gap between the two drugs.
Yan Yeyi has not announced its price or release schedule. Dova's AkaRx has announced that Doptelet's 40 mg tablet is priced at $9,000 and 60 mg is $13,500, which is higher than Leerink's previous forecast of $6,000. Some analysts expressed concerns about their high prices. It is difficult to predict how responders (medical insurance agencies) respond to this pricing policy, and in many cases, the cost is even higher than surgery. To ensure successful sales, both Dova and Yan Yeyi have developed a reimbursement support program and set up a team with experience in sales of liver disease.
There is also an urgent need for such drugs in the country. It is known that on March 19 this year, Fosun Pharma and AkaRx reached an agreement on Avatrombopag to obtain an exclusive license for the development and sale of the drug in mainland China and Hong Kong. Under the agreement, Fosun Pharma will assist AkaRx in developing Avatrombopag in China and Hong Kong to treat thrombocytopenia in patients with chronic liver disease and will support its development for other indications. Avatrombopag has been approved for chronic liver disease-related thrombocytopenia, and it is also undergoing chemotherapy-induced thrombocytopenia and chronic idiopathic thrombocytopenic purpura. In addition to being approved for chronic liver disease thrombocytopenia, Mulpleta is also being used clinically for immune thrombocytopenia.
According to the survey, the basic patent of Avattombopag will expire in 2023. The Lusutrombopag patent claimed by Yanyeyi Company is more complicated, and it receives multiple patent protections, and it will take some time to expire.
