The terms of the CVR Agreement will require the payment of up to an additional aggregate of $195 million in cash, (the "Milestone Payments"), upon the satisfaction of the following specific milestones, of which there is no assurance that any may be achieved:
� $5,000,000 upon the achievement of net sales of Marqibo (vincristine sulfate liposome injection) in excess of $30,000,000 in any calendar year;
� $10,000,000 upon the achievement of net sales of Marqibo in excess of $60,000,000 in any calendar year;
� $25,000,000 upon the achievement of net sales of Marqibo in excess of $100,000,000 in any calendar year;
� $50,000,000 upon the achievement of net sales of Marqibo in excess of $200,000,000 in any calendar year;
� $100,000,000 upon the achievement of net sales of Marqibo in excess of $400,000,000 in any calendar year; and
� $5,000,000 upon the receipt of marketing authorization from the FDA regarding Menadione Topical Lotion.
Marqibo is a liposomal vincristine and could substitute vincristine in various chemotherapeutical regimens. Currently vincristine is used for treatment of leukemia, Hodgkin disease, non-Hodgkin lymphomas, rhabdomyosarcoma, neuroblastoma, Wilms' tumor and in some non-oncology indications.
Interesting thought. Could also speculate that since Melphalan's most common side effect is oral mucositis, fusilev might become handy. Just kidding.
It is not about my sleep. Many analysts are using one year performance to recommend the stock. You should know that.
It does not matter. SP is higher than one year ago plus one day. 15% higher than lowest price. One year performance is positive.
"1) Their belief that Belinostat won't cannibalize Fol revenues" It won't, of course. They are two different classes of drugs with different MOA. Question is what drug will be prescribed after patient's remission on Folotyn. It could be either Belinostat or Istodax. Istodax belongs to the same category f drugs as Belinostat, HDACi. Istodax is already approved for PTCL. In many recent CCs Spectrum managed not to mentioned Istodax as a competitor. They do not want investors to know about it.
Could be a positive for share price since 1-year chart will look much better.
Exelixis: Positive Cometriq’s Survival Data (Phase III/CRPC) Expected in March; Cobimetinib Underappreciated, Opportunity as Part of Combo Therapy at $500M+ Potential
Using an analysis of Cometriq’s Phase II results in mCRPC, we shift our estimate for the announcement of survival data following the COMET-1 trial's 387-event mark from 2Q14 to late 1Q14. We apply a survival model to an estimated trajectory of patient enrollment to advance our previous estimate of the time of 387-event mark. We expect positive results from the COMET trial based on the 10.8 month mOS in Phase II and note that in a similar 3rdline patient population, Xtandi had a 7.9mo mOS in a single arm study, highlighting the lack of clinical options following Zytiga failure. The targeting of bone lesions appears to be a viable path to approval based on the approval of Xofigo, Algeta and Bayer’s radiation-based therapy, in May 2013.
We see upside to the Exelixis’ RCC trials for Cometriq, results in 2015. We see initial use of Cometriq in RCC being in the third and later lines of therapy based on the use of Afinitor as a control arm in their Phase III METEOR trial. We note that Cometriq is also in Phase II testing for earlier line treatment using Sutent as a control arm. We expect data from that trial in 2017.
We see cobimetinib as an underappreciated asset with development proceeding in combination with components of Roche’s oncology portfolio including its PD-1 checkpoint inhibitor. We estimate cobimetinib opportunity as part of a combination therapy at greater than $500M potential. We do not include combinations other than Zelboraf out of conservatism.
Source: Stifel/Sendek, February 6, 2014
Oncology Indication: Prostate
Keyword: Clinical Trials/Pipeline
One overlooked advantage of Marqibo therapy is "bridging" to potentially curative hematopoietic stem cell transplantation (HSCT). In phase 2 RALLY study Marqibo enabled bridging to HSCT in 11 of 65 (17%) subjects. Five of the 11 subjects were in CR at the time of post-Marqibo HSCT. Three of 11 subjects remain alive at greater than 28, 33, and 35 mos, respectively, after post-Marqibo HSCT. Bridging to HSCT was a key argument for approval by FDA since overall survival and response rate numbers are difficult to interpret in a single arm study.
"A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer".
Investigational New Drugs February 2014
Background Pralatrexate (FotolynTM; Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). Patients and methods This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m2 biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m2 weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Results Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Conclusions Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.
8. The results of many clinical trials completed in last 10 years clearly indicate that HDAC inhibitors, to which Belinostat belongs, have very limited therapeutic activities, especially in solid tumors. HDACi was exiting class of drugs 5-10 years ago but not now.
9. What is not encouraging is that even in some hematological cancers Belinostat did not show activity. It failed in MDS and AML recently. So far it is only good for PTCL.
10. On a positive side, Belinostat still could be used as an anticancer therapy in other indications beyond PTCL if combined with more effective drugs. However, it will take years of research to prove it, not to mention that competitors, MRK and JNJ, are much more resourceful.
Wouldn’t it be better for Spectrum to focus on other drugs in pipeline?
Grade 3/4 toxicities included: fatigue (8%), hyponatremia (8%), hypophosphatemia (8%) diarrhea (4%), thromboembolism (4%), transaminitis (4%), hypothyroidism (4%), thrombocytopenia (4%), dysphonia (4%), hypomagnesemia (4%), creatinine increase (4%) and proteinuria (4%). Conclusions: Cabozantinib has clinical activity in pts with relapsed or refractory mUC with manageable toxicities. Further studies are underway to correlate response to therapy with MET expression. Clinical trial information: NCT01688999.
Background: Translational studies have shown that shed MET levels in serum and urine of pts with UC correlate with stage and visceral metastases and that cabozantinib reverses HGF-driven UC cell growth and invasion. These data support the evaluation of cabozantinib in pts with mUC. Methods: In this phase II study, pts receive cabozantinib 60 mg daily in 28-day cycles. There are 3 study cohorts (1) mUC, (2) bone only mUC (3) metastatic rare bladder histology. The primary objective is to determine the response rate (RR) by RECIST. Response is assessed every 2 cycles. Tissue, blood, and urine were collected on all pts to test for MET/HGF and immune subsets. Results: 26 out of 55 pts have enrolled (19 M, 7 F): median age 62 (42-82) and median KPS of 80%. Primary sites include bladder (77%) and upper tract UC (23%). Prior therapy includes 30% pts with 1 regimen, 39% with 2, 15% with 3, 8% with 4 and 8% with 6. 81% of pts had visceral metastases (lung, liver and bone) and 19% lymph node only metastases. 23 pts (19 in cohort 1, 3 in cohort 2 and 1 in cohort 3) were evaluable for response after completing at least 4 weeks of therapy. In cohort 1, 2 pts achieved PR (1 remained on study for 10 months and 1 remains on study after 12 months of therapy); 7 pts had SD for at least 16 weeks (1 remained on study for 11 months); 10 had PD; 1 is too early to assess for response; 1 was removed before restaging for toxicity and 1 was removed for not meeting eligibility. The objective RR is 11% and SD 37% for a clinical benefit of 48%. In cohort 2, 1 of 3 pts had a near resolution of bone lesions on NaF PET/CT for 11 months. In cohort 3, only pt enrolled (squamous cell carcinoma of the bladder) achieved SD for 16 weeks. Mixed responses with regression of lung, bone or lymph nodes were observed in 30% of pts with PD.
"The company don’t have that much money to spend on trials and there are some which were requested by the FDA as part of the accelerated approvals."
I agree on that one. They must run:
1. Two Phase 3 trials with Folotyn
2. A phase 3 trial with Marqibo
3. A phase 3 trial with Belinostat if approved (waste of money)
4. A phase 3 trial with apaziquone if approved (chances are low).
The debt they must pay by cash or shares is only $16.5 million. It is in 5.75% convertible notes due in 2014. Not a big deal for $3.5 billion market cap company with $180 million in cash.
Was the investment worth it? Consider some facts and risks.
1. Spectrum paid $30M upfront, will pay $10M plus 1M shares (let’s say $10M) on acceptance plus $25M on approval. Total: $75M
2. Spectrum paid 70% for Phase 2 BELIEF trial and now is obliged to run BelChop phase 1 trial and later a large phase 3 trial paying 70% of all expenses. Let’s say, $150M for all, minimum. 1+2=$225M
3. Spectrum will pay TOPO mid-teen percentage royalty. Profit margins of 10 largest drugs companies are around 30%. If Spectrum is not out of range, royalty payments will cut profit from Belinostat sales substantially. Spectrum cannot demand high price for Belinostat because R/R PTCL is not a high unmet medical need any longer.
4. Accelerated approval of Belinostat means that company must run a confirmatory trial. If trial fails, the drug could be removed from the market.
5. Consider that Belinostat is a me-too drug with same mechanism of action as Istodax and will compete with Istodax in same patient population. By analysts’ opinion, peak revenue from Istodax in PTCL could reach $107M in 2016. In 2018 Istodax will go generic. If Belinostat is approved in 2014, it will have only 4 years to capture a decent share from Istodax in PTCL. And what would be the share of a drug with no clear advantage arriving second to the market 2-3 years later?
6. Belinostat is not superior to Istodax. Although less toxic, it produces less durable responses. Even Raj refused to answer when he was asked about how to compare these two drugs. Anyway, Spectrum cannot claim superiority for Belinostat without head-to-head trial.
7. Cycling between Folotyn and Belinostat treatments in R/R PTCL might happen in some patients. However, cycling between Folotyn and Istodax is also a possibility. And since Istodax is much more familiar to doctors, it will be their first choice.