Bad news for companies developing new treatments for osteoarthritis (OA) seemed to have little effect on the companies affected. The news came courtesy of the FDA, which stopped development of a class of compounds inhibiting the Nerve Growth Factor (NGF). Five companies were developing this class of compounds for treatment of pain associated with OA.
Pfizer (PFE) was the first to stop its drug, tanezumab, in June of 2010. At that time, it was speculated that the drug was in-fact so effective, that patients with OA forgot about their pain and started stressing their joints excessively. This lead to worsening cartilage degeneration or osteonecrosis of the femoral head. Amazingly enough, the trial was in subjects with OA of the knee, not hip.
Not much publicized was AstraZeneca’s (AZN) halting of MEDI-578 in July, right after the Pfizer announcement.
On Dec 28, the FDA placed Johnson and Johnson’s (JNJ) antibody to NGF, fulranumab, on clinical hold. That means no new patients can be recruited into the study. And Regeneron’s (REGN) REGN475/SAR164877, that was being developed jointly with Sanofi Aventis (SNY), was also placed on clinical hold.
That leaves only Abbott (ABT) in the game with ABT-110. It remains to be seen if this will become another COX2 story (with celebrex the only survivor). However, it is worth keeping in mind that the Abbott compound is also an antibody that it got last year from PanGenetics for $150 million. A hefty price to pay to play in the potential $11 billion market.
Wednesday, December 29, 2010
Monday, May 24, 2010
What NicOx's Naproxcinod tells us
Slightly more than a year ago, I got a call from a recruiter. She was looking for someone who could help a company file its NDA for a new anti-inflammatory compound. Having been involved in two phase III programs for osteoarthritis (OA), and having presented data to the FDA, I was pretty sure I could help the company, NicOx. However, I never heard from the company, and I moved on. So did the NicOx, but apparently not for the better. In September 2009, it filed an NDA for its lead compound, Naproxcinod, the indication being OA. And on May 15, it heard from the advisory committee that voted 14 to 1 (abstention) not to recommend approval of Naproxcinod for the treatment of OA. What happened, and what can we learn from it?
Science first. Naproxcinod is supposed to be a nitric oxide-donating anti-inflammatory compound and the first-in-class CINOD (Cyclooxygenase-Inhibiting Nitric Oxide Donator). The whole point of the nitric oxide donation is that nitric oxide causes vaso-dilatation, thereby decreasing the blood pressure and nullifying the cardiac side effects of non-steroidal anti-inflammatory compounds (NSAIDS) such as Naproxen which do their damage by their effect on prostaglandins. NicOx also wanted to show that Naproxcinod had better gastrointestinal tolerability and safety than Naproxen, thanks to the same nitric oxide. If this was to work out, NicOx would be have a truly competitive product.
In order to show just that, NicOx completed three clinical phase III studies – two for knee OA (301 and 302 studies) and one for hip (303 study), all for 13 weeks only. Cardiovascular outcomes data was collected till 52 weeks. The primary goal was the treatment of signs and symptoms of OA, but secondary goals included observing an effect on BP and endoscopic evaluation for ulcers and erosions. In study 301, two doses of Naproxcinod (750 mg bid and 375 mg bid) were superior to placebo but not to Naproxen (500 mg bid) in the WOMAC scores for OA. In study 302, Naproxcinod 750 mg bid was superior to placebo and Naproxen but the 375 mg dose was only superior to placebo. In study 303, Naproxcinod 750 mg bid was superior to placebo and essentially equivalent to Naproxen (the 375 mg bid dose was not studied). Since only the 750 mg bid dose was studied in two OA populations, it can be considered for filing. Looking at the FDA documents provides another look at the efficacy. I won’t go into the statistical mumbo jumbo, but there are several questions on the parameters the company chose to define efficacy. Total phase III exposure of the 750 mg bid dose was only, and I repeat only, 789 patients.
On the safety side, where the effect on BP and GI irritability comes in, the AE profile tells its own story. Among serious adverse events, or SAEs, Naproxcinod had an incidence of 0.3% (GI) and 0.2% (cardiac), worse than the 0.3% (GI) and less than 0.1% (cardiac) for Naproxen. Among all adverse events (not just serious), Naproxcinod 750 mg bid had an incidence of 56.4%, barely better (certainly not statistically better) than 58% for Naproxen.
This leads the FDA advisory committee to say “Based on findings from the two studies, there does not appear to be replicated evidence to support that naproxcinod has similar efficacy to naproxen” and conclude
1. Naproxcinod, at doses of 750 mg and 375 mg twice a day, is efficacious in the relief of signs and symptoms of osteoarthritis.
2. Naproxcinod has not been demonstrated to be non-inferior to naproxen.
3. The general safety profile of naproxcinod is consistent with that of the NSAID drug class.
In other words, maybe just as good as Naproxen for the treatment of OA, and then maybe not even as good. The cardiovascular division also had its say when it concluded:
1. The BP effect due to naproxcinod was not consistently less than baseline through the dosing interval. Naproxcinod is therefore not approvable as an antihypertensive agent.
2. Naproxen had a predominantly pressor effect through the dosing interval. Relative to equimolar doses of naproxen, with naproxcinod there appears to be a consistent lowering effect on SBP and DBP at peak (i.e. 1-4 hours post-dosing) but not at the end of the dosing interval.
3. More than two-fold changes in peak-trough effects were noted in some ABPM recordings suggesting that the proposed dosing regimen does not have a consistent effect throughout the dosing interval.
In other words, there was a short term beneficial effect on the blood pressure (1-4 hours after taking drug) but the benefit did not last through the day. Ironically, the committee was concerned about hypotension manifested as dizziness. Therefore, not only did they not approve a label claiming a cardiovascular benefit, but wanted a warning for hypotension, similar to that seen for nitroglycerin.
Finally, the division of gastroenterology commented on endoscopic studies 0002, 0005, and 0027 which were, at most, 6 weeks in length, comparing Naproxen, Naproxcinod, and placebo. Unfortunately, healthy volunteers were studied for two weeks in two studies, and erosions were the primary endpoint (the division likes six months in patients and ulcers, respectively). Only one study was in patients with ulcers as the primary endpoint and the study was for 6 weeks. In this study, the Naproxcinod 750 mg bid/Naproxen 500 mg bid ratio of ulcers was 0.7, with a p value of 0.07 (i.e. not statistically significant).
Compare the quality and quantity of data presented with that for Celecoxib, a drug that has the label the NicOx wanted. Specifically look at the duration of the studies, the primary endpoints and the patient numbers involved (source: Pfizer webpage)
Celecoxib Long-Term Arthritis Safety Study (CLASS) was a prospective long-term safety outcome study conducted in approximately 5,800 OA patients and 2,200 RA patients. Median exposures for Celexoxib (n = 3,987) and Diclofenac (n = 1,996) were 9 months while ibuprofen (n = 1,985) was 6 months. The primary endpoint of this outcome study was the incidence of complicated ulcers (gastrointestinal bleeding, perforation or obstruction).
Endoscopic Studies: A randomized, double-blind study in 430 RA patients was conducted in which an endoscopic examination was performed at 6 months. The incidence of endoscopic ulcers in patients taking Celecoxib 200 mg twice daily was 4% vs. 15% for patients taking Diclofenac SR 75 mg twice daily. The incidence of endoscopic ulcers was studied in two 12-week, placebo-controlled studies in 2157 OA and RA patients in whom baseline endoscopies revealed no ulcers.
What can we learn? Could things have been done differently? If NicOx had asked me a year ago, here is what I would have told them:
1. Naproxcinod would be approved if they went in purely as an NSAID since the data do support such a claim.
2. The endoscopic studies were too short, used the wrong kinds of subjects, and the wrong endpoints. There are enough studies showing the way (which is why I showed the Celecoxib data), and clear FDA guidelines, so I’m surprised that the company proceeded the way they did. It was clear that they were unlikely to get a claim for better GI tolerability. What they could have done was to get approval as an NSAID and to undertake these studies in phase IV. Better than getting an NDA rejected.
3. The cardiovascular effect was not sustained label was not likely. Once again, there are FDA guidelines, and precedence of other compounds, so I don’t see why the company chose the path it did. Especially with the data showing lack of sustained lowering of blood pressure.
Science first. Naproxcinod is supposed to be a nitric oxide-donating anti-inflammatory compound and the first-in-class CINOD (Cyclooxygenase-Inhibiting Nitric Oxide Donator). The whole point of the nitric oxide donation is that nitric oxide causes vaso-dilatation, thereby decreasing the blood pressure and nullifying the cardiac side effects of non-steroidal anti-inflammatory compounds (NSAIDS) such as Naproxen which do their damage by their effect on prostaglandins. NicOx also wanted to show that Naproxcinod had better gastrointestinal tolerability and safety than Naproxen, thanks to the same nitric oxide. If this was to work out, NicOx would be have a truly competitive product.
In order to show just that, NicOx completed three clinical phase III studies – two for knee OA (301 and 302 studies) and one for hip (303 study), all for 13 weeks only. Cardiovascular outcomes data was collected till 52 weeks. The primary goal was the treatment of signs and symptoms of OA, but secondary goals included observing an effect on BP and endoscopic evaluation for ulcers and erosions. In study 301, two doses of Naproxcinod (750 mg bid and 375 mg bid) were superior to placebo but not to Naproxen (500 mg bid) in the WOMAC scores for OA. In study 302, Naproxcinod 750 mg bid was superior to placebo and Naproxen but the 375 mg dose was only superior to placebo. In study 303, Naproxcinod 750 mg bid was superior to placebo and essentially equivalent to Naproxen (the 375 mg bid dose was not studied). Since only the 750 mg bid dose was studied in two OA populations, it can be considered for filing. Looking at the FDA documents provides another look at the efficacy. I won’t go into the statistical mumbo jumbo, but there are several questions on the parameters the company chose to define efficacy. Total phase III exposure of the 750 mg bid dose was only, and I repeat only, 789 patients.
On the safety side, where the effect on BP and GI irritability comes in, the AE profile tells its own story. Among serious adverse events, or SAEs, Naproxcinod had an incidence of 0.3% (GI) and 0.2% (cardiac), worse than the 0.3% (GI) and less than 0.1% (cardiac) for Naproxen. Among all adverse events (not just serious), Naproxcinod 750 mg bid had an incidence of 56.4%, barely better (certainly not statistically better) than 58% for Naproxen.
This leads the FDA advisory committee to say “Based on findings from the two studies, there does not appear to be replicated evidence to support that naproxcinod has similar efficacy to naproxen” and conclude
1. Naproxcinod, at doses of 750 mg and 375 mg twice a day, is efficacious in the relief of signs and symptoms of osteoarthritis.
2. Naproxcinod has not been demonstrated to be non-inferior to naproxen.
3. The general safety profile of naproxcinod is consistent with that of the NSAID drug class.
In other words, maybe just as good as Naproxen for the treatment of OA, and then maybe not even as good. The cardiovascular division also had its say when it concluded:
1. The BP effect due to naproxcinod was not consistently less than baseline through the dosing interval. Naproxcinod is therefore not approvable as an antihypertensive agent.
2. Naproxen had a predominantly pressor effect through the dosing interval. Relative to equimolar doses of naproxen, with naproxcinod there appears to be a consistent lowering effect on SBP and DBP at peak (i.e. 1-4 hours post-dosing) but not at the end of the dosing interval.
3. More than two-fold changes in peak-trough effects were noted in some ABPM recordings suggesting that the proposed dosing regimen does not have a consistent effect throughout the dosing interval.
In other words, there was a short term beneficial effect on the blood pressure (1-4 hours after taking drug) but the benefit did not last through the day. Ironically, the committee was concerned about hypotension manifested as dizziness. Therefore, not only did they not approve a label claiming a cardiovascular benefit, but wanted a warning for hypotension, similar to that seen for nitroglycerin.
Finally, the division of gastroenterology commented on endoscopic studies 0002, 0005, and 0027 which were, at most, 6 weeks in length, comparing Naproxen, Naproxcinod, and placebo. Unfortunately, healthy volunteers were studied for two weeks in two studies, and erosions were the primary endpoint (the division likes six months in patients and ulcers, respectively). Only one study was in patients with ulcers as the primary endpoint and the study was for 6 weeks. In this study, the Naproxcinod 750 mg bid/Naproxen 500 mg bid ratio of ulcers was 0.7, with a p value of 0.07 (i.e. not statistically significant).
Compare the quality and quantity of data presented with that for Celecoxib, a drug that has the label the NicOx wanted. Specifically look at the duration of the studies, the primary endpoints and the patient numbers involved (source: Pfizer webpage)
Celecoxib Long-Term Arthritis Safety Study (CLASS) was a prospective long-term safety outcome study conducted in approximately 5,800 OA patients and 2,200 RA patients. Median exposures for Celexoxib (n = 3,987) and Diclofenac (n = 1,996) were 9 months while ibuprofen (n = 1,985) was 6 months. The primary endpoint of this outcome study was the incidence of complicated ulcers (gastrointestinal bleeding, perforation or obstruction).
Endoscopic Studies: A randomized, double-blind study in 430 RA patients was conducted in which an endoscopic examination was performed at 6 months. The incidence of endoscopic ulcers in patients taking Celecoxib 200 mg twice daily was 4% vs. 15% for patients taking Diclofenac SR 75 mg twice daily. The incidence of endoscopic ulcers was studied in two 12-week, placebo-controlled studies in 2157 OA and RA patients in whom baseline endoscopies revealed no ulcers.
What can we learn? Could things have been done differently? If NicOx had asked me a year ago, here is what I would have told them:
1. Naproxcinod would be approved if they went in purely as an NSAID since the data do support such a claim.
2. The endoscopic studies were too short, used the wrong kinds of subjects, and the wrong endpoints. There are enough studies showing the way (which is why I showed the Celecoxib data), and clear FDA guidelines, so I’m surprised that the company proceeded the way they did. It was clear that they were unlikely to get a claim for better GI tolerability. What they could have done was to get approval as an NSAID and to undertake these studies in phase IV. Better than getting an NDA rejected.
3. The cardiovascular effect was not sustained label was not likely. Once again, there are FDA guidelines, and precedence of other compounds, so I don’t see why the company chose the path it did. Especially with the data showing lack of sustained lowering of blood pressure.
Friday, May 7, 2010
A clinical look at Human Genome's lupus drug
On Tuesday, April 20, Human Genome Sciences (HGSI) released longer term data from its Bliss 76 Phase III study in Lupus, leading to a stock drop. First some back ground.
HGSI is developing Belimumab, an antibody to immature B cells, for the treatment of SLE by targeting the B Lymphocyte Stimulator (BLyS). Treatment with the antibody prevents B cells from maturing into auto-antibody secreting plasma cells. The Phase II data had been insipid, but data analysis by the company showed that patients who were sero-positive (i.e. HEp-2 ANA ≥ 1:80 and/or anti-dsDNA ≥ 30 IU/mL) were better responders than sero-negative patients. The Phase III studies were designed with that in mind. This is an important point that the reader should understand since not all SLE patients are sero-positive as defined in this trial - about 50% of patient in my practice are, and others report rates between 50 and 80% (which shows the heterogenous nature of the disease).
Two Phase III trials were conducted, one a 52 week trial (BLISS 52) in Asia, South America, and Eastern Europe, and the other a 76 week trial (BLISS 76) in North America and Western Europe. Doses looked at were 10 mg/kg and 1 mg/kg on a background of standard of care. At 52 weeks, both studies reported positive data with the 10 mg/kg dose. The response rates are below:
STUDY 10 MG/KG PLACEBO DIFF
BLISS 52 57.6 43.6 14
BLISS 76 43.2 33.8 9.4
Based on the above, it is clear that there is enough evidence to approve the drug. This was truly great news for us who have had no new treatment for our lupus patients in the past 50 years.
Now to the news from April 20. The 76 week data from BLISS 76 was released, and the company said 38.5% of patients responded to the 10 mg/kg dose (down from 43.2% at 52 weeks, a drop of 4.7%) compared to 32.4% of patients treated with a placebo (down from 33.8% at 52 weeks, a drop of 1.4%). The difference between the 10 mg/kg dose and placebo was not statistically significant. More curiously, the previously less appealing dose of 1 mg/kg was in many measures better than the 10 mg/kg dose. So, what is going on? And what are its implications?
It is unclear why the response rates dropped with time. Was it due to antibodies to the antibodies? After all, lupus patients are very adept at making antibodies. Or was it due to tachyphylaxis? Or some other reason?
The implications of this phenomenon are significant. Lets do the maths. Of my 20 patients who can be treated with Belimumab, lets say I put them all on it at (speculatively) $20,000 a year. That nets the company $400,000. After a year, I have to stop treating them, and can only use Belimumab on new patients (lets say about 4). Now the company is netting only $80,000, down from $400,000. But there is another, more important point. This relates to the question of why the effect wears off - does the effect, in fact, go into reverse? In other words, will there be a rebound? Will the disease, once the Belimumab is stopped, become worse than it was originally? Some may argue that no such rebound was seen in the clinical studies, but one must keep in mind that patients are not followed beyond a week or so after their last visit, so a rebound would not be captured by the study. So while the PI (principal investigator at the site) would know about it (assuming s/he knew the randomization), the companies would not.
Compare that to the anti-TNF story - one of the great advantages of anti-TNFs such as Enbrel (Pfizer and Amgen) and Humira (Abbott) used in the treatment of RA is that their efficay does not wane with time. No wonder they have 8 - 10 year safety and efficacy data. Similar long term safety and efficacy data would be very useful for Benlysta.
HGSI is developing Belimumab, an antibody to immature B cells, for the treatment of SLE by targeting the B Lymphocyte Stimulator (BLyS). Treatment with the antibody prevents B cells from maturing into auto-antibody secreting plasma cells. The Phase II data had been insipid, but data analysis by the company showed that patients who were sero-positive (i.e. HEp-2 ANA ≥ 1:80 and/or anti-dsDNA ≥ 30 IU/mL) were better responders than sero-negative patients. The Phase III studies were designed with that in mind. This is an important point that the reader should understand since not all SLE patients are sero-positive as defined in this trial - about 50% of patient in my practice are, and others report rates between 50 and 80% (which shows the heterogenous nature of the disease).
Two Phase III trials were conducted, one a 52 week trial (BLISS 52) in Asia, South America, and Eastern Europe, and the other a 76 week trial (BLISS 76) in North America and Western Europe. Doses looked at were 10 mg/kg and 1 mg/kg on a background of standard of care. At 52 weeks, both studies reported positive data with the 10 mg/kg dose. The response rates are below:
STUDY 10 MG/KG PLACEBO DIFF
BLISS 52 57.6 43.6 14
BLISS 76 43.2 33.8 9.4
Based on the above, it is clear that there is enough evidence to approve the drug. This was truly great news for us who have had no new treatment for our lupus patients in the past 50 years.
Now to the news from April 20. The 76 week data from BLISS 76 was released, and the company said 38.5% of patients responded to the 10 mg/kg dose (down from 43.2% at 52 weeks, a drop of 4.7%) compared to 32.4% of patients treated with a placebo (down from 33.8% at 52 weeks, a drop of 1.4%). The difference between the 10 mg/kg dose and placebo was not statistically significant. More curiously, the previously less appealing dose of 1 mg/kg was in many measures better than the 10 mg/kg dose. So, what is going on? And what are its implications?
It is unclear why the response rates dropped with time. Was it due to antibodies to the antibodies? After all, lupus patients are very adept at making antibodies. Or was it due to tachyphylaxis? Or some other reason?
The implications of this phenomenon are significant. Lets do the maths. Of my 20 patients who can be treated with Belimumab, lets say I put them all on it at (speculatively) $20,000 a year. That nets the company $400,000. After a year, I have to stop treating them, and can only use Belimumab on new patients (lets say about 4). Now the company is netting only $80,000, down from $400,000. But there is another, more important point. This relates to the question of why the effect wears off - does the effect, in fact, go into reverse? In other words, will there be a rebound? Will the disease, once the Belimumab is stopped, become worse than it was originally? Some may argue that no such rebound was seen in the clinical studies, but one must keep in mind that patients are not followed beyond a week or so after their last visit, so a rebound would not be captured by the study. So while the PI (principal investigator at the site) would know about it (assuming s/he knew the randomization), the companies would not.
Compare that to the anti-TNF story - one of the great advantages of anti-TNFs such as Enbrel (Pfizer and Amgen) and Humira (Abbott) used in the treatment of RA is that their efficay does not wane with time. No wonder they have 8 - 10 year safety and efficacy data. Similar long term safety and efficacy data would be very useful for Benlysta.
Health Care "Reform" Bill and Biotechnology companies
Buried in the pages of the recently passed Health Care "Reform" Bill are some worthy incentives for small biotechnology companies. They are mentioned under Therapeutic Discovery Project Tax Credit. The program is similar to the tax credits for investments in certain energy projects. While the guidelines have not been fully vetted, the program provides a credit in the amount of 50% of investments in qualified therapeutic discovery projects and qualifying investments made in 2009 and 2010. It is limited to small companies, as defined by having fewer than 250 employees and covers projects that are designed to:
1. Treat or prevent diseases or conditions by conducting pre-clinical studies activities, clinical trials, or carrying out research protocols, for the purpose of securing approval of a drug or a biologic.
2. Determine the molecular factors related to diseases or conditions by developing molecular diagnostics to guide therapeutic decisions, or
3. Develop process, technologies, or products to further the delivery or administration of therapeutics.
While the "Reform" Bill has much that is lamentable, this little tidbit is certainly good news for the small biotechnology and pharmaceutical companies.
1. Treat or prevent diseases or conditions by conducting pre-clinical studies activities, clinical trials, or carrying out research protocols, for the purpose of securing approval of a drug or a biologic.
2. Determine the molecular factors related to diseases or conditions by developing molecular diagnostics to guide therapeutic decisions, or
3. Develop process, technologies, or products to further the delivery or administration of therapeutics.
While the "Reform" Bill has much that is lamentable, this little tidbit is certainly good news for the small biotechnology and pharmaceutical companies.
Monday, April 12, 2010
Keryx Biopharma (NASDAQ:KERX) Product Development Update
Keryx Biopharmaceuticals, Inc. (NASDAQ:KERX) is an emerging biopharma company that has a pair of lead compounds in late stage development: Perifosine for the treatment of cancer and Zerenex for patients suffering from renal disease.
Last December, Keryx announced the initiation of a Phase 3 pivotal study of Perifosine (KRX-0401), the Company's PI3K/Akt pathway inhibitor (a cell signaling pathway that disrupts the normal cell cycle / programmed cell death and leads to chemotherapy drug resistance in some cancer cells), in multiple myeloma patients under a Special Protocol Assessment (SPA) with the FDA with Fast Track designations for this indication.
Perifosine is in-licensed by Keryx from Aeterna Zentaris. Keryx expects a patient recruitment period of approximately 16-18 months and expects to report data from this study during 2H11. In addition, a refractory metastatic colorectal cancer (mCRC) study under SPA is expected to begin 2Q10 with projected completion 2H11.
During the first week of 2010, Keryx announced that it has reached agreement with the FDA regarding a SPA for the design of a Phase 3 clinical program for Zerenex (ferric citrate), which is the Company's iron-based phosphate binder for the treatment of elevated serum phosphorous levels (hyperphosphatemia occurs in the majority of dialysis patients, resulting in serious medical complications such as blood vessel calcification and skeletal deformities since phosphate is a major component of bone along with calcium) in patients with end-stage renal disease (ESRD) that are on dialysis.
Zerenex works by forming iron-phosphate complexes in the gut that are not absorbed since patients with ESRD are prone to electrolyte disorders such as elevated phosphorus due to the absence of normal kidney function. In accordance with the Company's SPA agreement with the FDA, the Phase 3 clinical program for Zerenex will consist of two clinical studies, including (1) a short-term efficacy study that is expected to commence by the end of 1Q10 with date expected during 2H10; and (2) a long-term safety and efficacy study that is expected to begin mid-2010 with data expected and a NDA filing expected during 1H12.
Keryx has retained all key commercial rights for its two lead compounds and has the resources to complete Phase 3 development for both of its lead compounds, which provides more leverage in partnership discussions. The estimated cash burn rate for 2010 is $1.3 million per month or approximately $4 million per quarter and $16 million for the entire year.
This is a sponsored post placed by IR GRO on behalf of ProActive Capital. Please visit the ProActive News Room for more details on Keryx.
Wednesday, February 24, 2010
Access Pharma (ACCP.OB) Product Development Update – Sponsored Post
Access Pharmaceuticals (OTC: ACCP.OB, “Access”) develops and commercializes products for the treatment and supportive care of cancer patients, including:
- MuGard, an FDA-approved rinse for the management of patients with oral mucositis, a debilitating side effect of various cancer treatments
- ProLindac, now in Phase II clinical testing of patients with ovarian cancer
- The Cobalamin Platform, a drug delivery system for the oral administration of large molecules that are currently administered via injection (insulin, human growth hormone, fertility drugs, etc.)
MuGard has been commercially launched by Access' partner, SpePharm, in six European countries, including the UK, Germany, Italy, Norway, Greece and Sweden. Over 15,000 bottles of MuGard have been used by over 2,000 patients to date. Access is now conducting pre-marketing activities, including ramping of commercial production, with the goal of a U.S. commercial launch by April 2010.
ProLindac is a next-generation DACH platinum anti-cancer compound which includes a proprietary nano-polymer drug delivery vehicle that allows for over ten-times the dose of platinum to be delivered in a targeted manner to cancer cells, with a much better safety profile compared to standard platinum-based drugs which cause significant and cumulative neurotoxicity.
Access will conduct a combination study evaluating ProLindac with Taxol (paclitaxel) for second-line treatment of platinum pre-treated patients with advanced ovarian cancer. This is a multi-center study being conducted in Europe in up to 25 patients with primary efficacy endpoint goal of achieving at least a 63% response rate. Access expects to begin patient dosing by April 2010.
The Cobalamin Platform is a drug delivery technology that involves coating a nano-particle with a vitamin B-12 analog (cobalamin) that binds to intrinsic factor in the gut and triggers binding to cellular receptors which absorb the entire package, resulting in exponential increases in absorption through the gut of large molecule drugs/hormones typically administered by injection.
In June 2009, Access announced that two bio-pharmaceutical companies would conduct preclinical, proof-of-concept studies in animals (rat and dog models of diabetes) before proceeding to more formal negotiations for the Company's oral, long-acting (basal) insulin product candidate. Final results from the non-exclusive collaborators are possible during Q1 2010.
For more information on Access, visit the ProActive Capital Newsroom at www.proactivenewsroom.com.
This post was placed by IR GRO.
Wednesday, February 3, 2010
Glaxo's helping hand to underserved markets
New models for drug development, especially in big pharma, are being experimented by different companies. Eli Lilly (LLY) and Glaxo SmithKline (GSK) have two different models. These models do not throw out the old ones - but do offer additional routes going forward. I mentioned Lilly in my previous post.
GSK has come up with an opposite approach where it is offering its library of compounds to researchers in a certain therapeutic area (under-served tropical diseases). For example, it is offering 13,500 compounds that appear to work in malaria. GSK will let other scientists try to develop malaria drugs -- free from royalties or other payments to GSK. They were narrowed down from more than 2 million compounds.
More unusual is its open lab project. GSK plans to give up to 60 outside scientists from around the globe access to what it called the “Open Lab," at an existing company research lab in Spain. Researchers from universities, foundations, etc will be able to use the facilities to try to develop new medicines for diseases plaguing poor countries.
GSK is to start a foundation to fund research and idea sharing, kicking in $8 million initially. It also plans to work with the Emory Institute for Drug Discovery. I have worked a bit with the Emory Institute of Drug Discovery and know they have an excellent drug development team, but have not learnt anything from them about what their exact role in this project is going to be.
While a small fraction of overall R&D efforts, it nevertheless is a significant departure from business as usual. And while GSK does not expect to get royalties, the halo effect, especially with health care reform in the spotlight, cannot be neglected. One could criticize GSK in pointing out that the company does not have much to lose by sharing data in neglected diseases – and that it is not doing so in the more lucrative markets such as oncology.But I doubt that the millions of patients suffering from malaria and TB will support such criticism. New models for drug development, especially in big pharma, are being experimented by different companies. Eli Lilly and Glaxo SmithKline have two different models. These models do not throw out the old ones - but do offer additional routes going forward.
Lilly's PD2 initiative
New models for drug development, especially in big pharma, are being experimented by different companies. Eli Lilly (LLY) and Glaxo SmithKline (GSK) have two different models. These models do not throw out the old ones - but do offer additional routes going forward.
Lilly has a Phenotypic Drug Discover Initiative, (or PD2), launched in 2009 (http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=389589). Lilly solicits compounds from other companies so long as they are in certain therapeutic areas (oncology, diabetes, osteoporosis, and Alzheimer's Disease). Compound structures are sent to Lilly electronically where they are evaluated using modeling and simulation. If the compound passes the screen, the physical compound is sent to Lilly for further testing. If the compound passes the physical test, the fun begins.
All testing by Lilly is free and IP remains with the originating company or institution. What Lilly gets in return is the first right to exclusively negotiate an agreement. If talks break down, the originator keeps all the data generated by Lilly.
Having had some personal experience through a biotechnology company (IMC Biotechnology), I think this is a very interesting approach. The company submitted 9 compounds to Lilly and one of them went through the screening process. The software had some minor glitches but the Lilly representatives were very helpful in addressing those glitches.
I think this is a great way for Lilly to expand its repertoire of compounds beyond those invented by its chemists. Certainly one way of going beyond the NIH (not invented here) syndrome.
Lilly has a Phenotypic Drug Discover Initiative, (or PD2), launched in 2009 (http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=389589). Lilly solicits compounds from other companies so long as they are in certain therapeutic areas (oncology, diabetes, osteoporosis, and Alzheimer's Disease). Compound structures are sent to Lilly electronically where they are evaluated using modeling and simulation. If the compound passes the screen, the physical compound is sent to Lilly for further testing. If the compound passes the physical test, the fun begins.
All testing by Lilly is free and IP remains with the originating company or institution. What Lilly gets in return is the first right to exclusively negotiate an agreement. If talks break down, the originator keeps all the data generated by Lilly.
Having had some personal experience through a biotechnology company (IMC Biotechnology), I think this is a very interesting approach. The company submitted 9 compounds to Lilly and one of them went through the screening process. The software had some minor glitches but the Lilly representatives were very helpful in addressing those glitches.
I think this is a great way for Lilly to expand its repertoire of compounds beyond those invented by its chemists. Certainly one way of going beyond the NIH (not invented here) syndrome.
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